tbuckley/cabot-search huggingface dataset:
Development of a health status measure for older African-American women with type 2 diabetes.
Authors: T A Elasy, C D Samuel-Hodge, R F DeVellis, A H Skelly, A S Ammerman, T C Keyserling
Journal: Diabetes Care (2000)

OBJECTIVE: To develop a health status measure in older African-American women with type 2 diabetes. RESEARCH DESIGN AND METHODS: African-American women, age &amp;gt; or =40 years with type 2 diabetes, were recruited from central North Carolina to participate in three sequential phases: 1) Seven focus groups were convened and transcripts evaluated to generate questions and identify plausible domains; 2) Ten one-on-one cognitive response interviews were performed to ensure clarity and cultural appropriateness of the questions; and 3) 217 women participated in psychometric evaluation to establish the internal consistency and validity of the instrument. RESULTS: Three broad categories--mental, physical, and social well-being--captured important issues generated during the focus groups. "My diabetes" was added during the cognitive response interviews as a way of separating the impact of diabetes from coexisting issues that affect health status. The response option was changed from a six- to a four-point Likert scale to accommodate subject preference. Using principal components and subsequent promax rotation, we identified two hierarchical domains (mental and social well-being) and a physical symptom index. The internal consistency (Cronbach's alpha) of the mental and social well-being subscales are 0.83 and 0.93, respectively. A priori hypothesized correlations between subscales along with each subscale and glycated hemoglobin, diabetes duration, physical activity, and a perceived health competence scale helped establish the construct validity of the instrument. CONCLUSIONS: A culturally appropriate disease-specific health status measure for older African-American women with type 2 diabetes has been developed. We have established the internal consistency, construct validity, and factor analytic properties of the measure. This measure should prove useful for investigators who seek a health status instrument that addresses issues germane to African-American women with type 2 diabetes.
Mobilization of Bone Marrow Cells by G-CSF Rescues Mice from Cisplatin-Induced Renal Failure, and M-CSF Enhances the Effects of G-CSF
Authors: Masayoshi Iwasaki, Yasushi Adachi, Keizo Minamino, Yasuhiro Suzuki, Yuming Zhang, Mitsuhiko Okigaki, Keiji Nakano, Yasushi Koike, Jianfeng Wang, Hiromi Mukaide, Shigeru Taketani, Yasukiyo Mori, Hakuo Takahashi, Toshiji Iwasaka, Susumu Ikehara
Journal: Journal of the American Society of Nephrology (2005)

Cisplatin, which is a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. This article examines whether G-CSF and/or M-CSF rescues mice from renal failure induced by cisplatin. BALB/c mice received intraperitoneal injections with or without G-CSF and/or M-CSF for 5 d (from day -5 to day -1). The day after the last injection of G-CSF and/or M-CSF (day 0), the mice received an intraperitoneal injection of cisplatin. When pretreated with G-CSF or G-CSF + M-CSF, the mice showed longer survival and lower serum creatinine and blood urea nitrogen levels than mice that had been received injections of M-CSF or saline. Histologically, pretreatment with G-CSF or G-CSF + M-CSF attenuated the damage to renal tubules induced by cisplatin. BALB/c mice that had received a transplant of bone marrow cells of enhanced green fluorescent protein (EGFP)-transgenic mice ([EGFP-->BALB/c] mice) were treated with or without G-CSF and/or M-CSF, followed by injection of cisplatin as well as above. [EGFP-->BALB/c] mice that were treated with G-CSF or G-CSF + M-CSF showed a significantly higher number of EGFP(+) tubular epithelial cells in the kidney than mice that were treated with only M-CSF or saline. These results suggest that bone marrow cells mobilized by G-CSF accelerate the improvement in renal functions and prevent the renal tubular injury induced by cisplatin and that M-CSF enhances the effects of G-CSF.
Germline KRAS mutations cause Noonan syndrome
Authors: Suzanne Schubbert, Martin Zenker, Sara L Rowe, Silke Böll, Cornelia Klein, Gideon Bollag, Ineke van der Burgt, Luciana Musante, Vera Kalscheuer, Lars-Erik Wehner, Hoa Nguyen, Brian West, Kam Y J Zhang, Erik Sistermans, Anita Rauch, Charlotte M Niemeyer, Kevin Shannon, Christian P Kratz
Journal: Nature Genetics (2006)
Identification of the SH2 Domain Binding Protein of Bruton’s Tyrosine Kinase as BLNK—Functional Significance of Btk-SH2 Domain in B-Cell Antigen Receptor-Coupled Calcium Signaling
Authors: Shoji Hashimoto, Akihiro Iwamatsu, Masamichi Ishiai, Katsuya Okawa, Tomoki Yamadori, Masato Matsushita, Yoshihiro Baba, Tadamitsu Kishimoto, Tomohiro Kurosaki, Satoshi Tsukada
Journal: Blood (1999)
Protrusion of the lung apex through Sibson's fascia in infancy.
Authors: M Grunebaum, N T Griscom
Journal: Thorax (1978)

Apical 9herniation9 of the lung is an unusual protrusion of the lung and its pleural coverings through the superior aperture of the thorax. It is supposedly caused by weakness of Sibson9s fascia. The phenomenon is an anatomical variation and not a disease entity; however, it must be recognised in order to avoid inappropriate surgery. The condition apparently disappears spontaneously with growth.
Cardiac impairment or heart failure?: What about “cardiovascular insufficiency syndrome”?
Authors: J David Mitchell
Journal: BMJ (2005)

The release of the government's latest report on health inequalities on 11 August was curious. 1 2 Reminiscent of the covert release of the Black report on August bank holiday in 1980, the report appeared when the minister for public health was on holiday and her deputy unavailable. Personal trainersIn July 2003 the government stated that there would be an annual report from the Department of Health on health inequality indicators related to the health inequality targets.Nothing appeared for more than two years, although the data that were eventually released had been available for some time, 3 and when they did appear it was, conveniently, after the election.Even stranger, the press release for the latest report deflected attention from the key finding of widening inequalities in life expectancy and infant mortality by headlining the 12 "early adopter sites" with their "health trainers." 4 The minister said, "Many people have difficulty in changing to a healthier way of life . . .Health trainers are one of the many initiatives in the white paper which will help narrow this gap by supporting people to make healthier choices in their daily lives." 4 To Labour traditionalists, opposed to victim blaming approaches to health promotion, this may have triggered memories of Conservative minister Edwina Currie admonishing the poor to buy cheap but healthy food.To New Labour, however, it may be grist to the mill.
FIFA's commitment to doping-free football
Authors: J S Blatter
Journal: British Journal of Sports Medicine (2006)

The Federation Internationale de Football Association (FIFA) has a clear vision for its anti-doping strategy in football: make the game doping free. We have to protect our players from harm and ensure that they can compete on equal grounds. As we are dealing with ambitious and self-responsible professionals, FIFA’s anti-doping strategy relies on education and prevention, thereby we ensure their support in our fight against doping.

Naturally, FIFA aims at interfering as less as possible with the normal course of matches and tournaments and the recreation …
How to quantify an arterial stenosis: a study on the femoral arteries of dog and man
Authors: J. P DE JONG, N. WESTERHOF, G. ELZINGA
Journal: Cardiovascular Research (1986)

The blood supply to the femoral bed was studied in anaesthetised dogs before and after producing arterial stenoses. The blood supply system consisted of the vessels proximal to the site of measurement in the femoral artery and was characterised by a supply graph, which related mean perfusion pressure to mean flow. The different pressures and flows were obtained using an artificial periphery, the impedance of which was changed from beat to beat. The supply graph was approximated by a parabola with two parameters: the intercepts with the pressure and flow axes, the latter indicating the maximum mean flow. For constant aortic pressure the maximum mean flow appeared to be linearly related to the cross sectional area of the stenosed section (r = 0.98). Maximum mean flow was already considerably reduced before the stenosis became critical--that is, before physiological flow was measurably diminished. The change in maximum mean flow was therefore used to quantify the haemodynamic effects of stenoses that were less than critical. Blood supply graphs of the superficial femoral arteries were determined also in seven patients undergoing a femoropopliteal bypass operation. The maximum mean flow correlated well with the degree of obstruction determined from the preoperative angiograms (r = 0.90).
Effect of cholestyramine on the fecal excretion of intravenously administered cholesterol-4-14C and its degradation products in a hypercholesterolemic patient
Authors: Richard B. Moore, Catherine A. Crane, Ivan D. Frantz
Journal: Journal of Clinical Investigation (1968)

The effect of cholestyramine on the fecal excretion of bile acids and neutral sterols was measured in a hypercholesterolemic patient on a low fat, high polyunsaturated fatty acid-containing diet after the intravenous injection of cholesterol-4-(14)C. A significant (16%) lowering of serum cholesterol concentration was accompanied by a 3.2-fold increase in fecal bile acid excretion but no change in neutral sterol output. The increased bile acid loss was adequate to account for the observed fall in serum cholesterol level. The implications of these findings were discussed.
Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation
Authors: Liyan Yang, Lauren Cohn, Dong-Hong Zhang, Robert Homer, Anuradha Ray, Prabir Ray
Journal: The Journal of Experimental Medicine (1998)

The molecular mechanisms that contribute to an eosinophil-rich airway inflammation in asthma are unclear. A predominantly T helper 2 (Th2)-type cell response has been documented in allergic asthma. Here we show that mice deficient in the p50 subunit of nuclear factor (NF)- κB are incapable of mounting eosinophilic airway inflammation compared with wild-type mice. This deficiency was not due to a block in T cell priming or proliferation in the p50−/− mice, nor was it due to a defect in the expression of the cell adhesion molecules VCAM-1 and ICAM-1 that are required for the extravasation of eosinophils into the airways. The major defects in the p50−/− mice were the lack of production of the Th2 cytokine interleukin 5 and the chemokine eotaxin, which are crucial for proliferation and for differentiation and recruitment, respectively, of eosinophils into the asthmatic airway. Additionally, the p50−/− mice were deficient in the production of the chemokines macrophage inflammatory protein (MIP)-1α and MIP-1β that have been implicated in T cell recruitment to sites of inflammation. These results demonstrate a crucial role for NF-κB in vivo in the expression of important molecules that have been implicated in the pathogenesis of asthma.
FDA limits research of former AHA president for submitting false information
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Just days before he completed his year as president of the American Heart Association on 30 June, Dr David Faxon signed a consent agreement with the Food and Drug Administration limiting his clinical research.

On 19 June 2002 Dr Faxon agreed that for three years he would not be the principal investigator for more than two FDA regulated clinical investigations at any one time, and that he would not be the principal clinical investigator for a study that enrolled more than 25 subjects. …
Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition
Authors: Andreas Meyer-Lindenberg, Richard E. Straub, Barbara K. Lipska, Beth A. Verchinski, Terry Goldberg, Joseph H. Callicott, Michael F. Egan, Stephen S. Huffaker, Venkata S. Mattay, Bhaskar Kolachana, Joel E. Kleinman, Daniel R. Weinberger
Journal: Journal of Clinical Investigation (2007)

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), encoded by PPP1R1B, is a pivotal integrator of information in dopaminoceptive neurons, regulating the response to neuroleptics, psychotomimetics, and drugs of abuse, and affecting striatal function and plasticity. Despite extensive preclinical work, there are almost no data on DARPP-32 function in humans. Here, we identify, through resequencing in 298 chromosomes, a frequent PPP1R1B haplotype predicting mRNA expression of PPP1R1B isoforms in postmortem human brain. This haplotype was associated with enhanced performance on several cognitive tests that depend on frontostriatal function. Multimodal imaging of healthy subjects revealed an impact of the haplotype on neostriatal volume, activation, and the functional connectivity of the prefrontal cortex. The haplotype was associated with the risk for schizophrenia in 1 family-based association analysis. Our convergent results identify a prefrontal-neostriatal system affected by variation in PPP1R1B and suggest that DARPP-32 plays a pivotal role in cognitive function and possibly in the pathogenesis of schizophrenia.
Effect of I:E ratio on delivery of colistimethate sodium from breath-enhanced and breath-activated nebulizers
Authors: Sarah Byrne, Danielle Jeffrey, Ross Hatley
Journal: European Respiratory Journal (2013)

Drug delivery via a nebulizer differs depending on the nebulizer/compressor combination and the principle of operation of the nebulizer. Consequently, while breathing patterns (BPs) with different inhalation:exhalation (I:E) ratios can affect delivered dose (DD), this effect differs depending upon the principle of operation.

An in vitro investigation into the effect of different I:E ratios on the dose of colistimethate sodium (CMS) delivered via nebulizers was undertaken. Here, results from the breath-activated I-neb AAD System (I-neb) and 2 breath-enhanced nebulizers with TurboBoy SX compressors, the LC Sprint (LCS) and the LC Plus (LCP), are compared. Each nebulizer (n=3, run in triplicate) was loaded with CMS 1 MIU (reconstituted in water, I-neb=1 mL; LCS/LCP=3 mL). Nebulizers were attached to a breathing simulator and run until sputter +60 s with 4 different BPs. Dose delivered to a filter with each BP was analyzed by bioassay.

View this table:

Table 1: % DD, compared with the 1:1 I:E ratio, for each nebulizer with each BP.





Dose delivered via LCS and LCP was proportional to the duration of inhalation. In contrast, a relatively consistent dose was delivered by I-neb, regardless of BP. Aspects of BP, including I:E ratio, may be influenced by pathophysiology; independence of DD from BP is therefore likely to minimize dose variability in the clinical setting.
Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris.
Authors: J D Horowitz, C A Henry, M L Syrjanen, W J Louis, R D Fish, T W Smith, E M Antman
Journal: Circulation (1988)

The vasodilator effects of nitroglycerin (NTG) are mediated via activation of guanylate cyclase; this process is believed to require the availability of free sulfhydryl groups. Previous studies in man have shown that the sulfhydryl donor N-acetylcysteine (NAC) potentiates the systemic and coronary vasodilator effects of NTG. Furthermore, interaction of NTG and NAC may lead to the formation of S-nitroso-NAC, which strongly inhibits platelet aggregation. The effects of intravenous NTG combined with intravenous NAC (5 g 6 hourly) were compared with those of intravenous NTG alone in a double-blind trial in 46 patients with severe unstable angina pectoris unresponsive to conventional treatment, which included calcium antagonists and cutaneous nitrates in all but one patient. Treatment with NTG/NAC (24 patients) and that with NTG alone (22 patients) was associated with a similar frequency of episodes of chest pain and of increments in NTG infusion rate for pain control (10 vs 17; p = NS). The NTG/NAC group had a significantly lower incidence of acute myocardial infarction than the NTG/placebo group (three vs 10 patients; p = .013). Symptomatic hypotension occurred frequently in the NTG/NAC group (seven vs 0 patients; p = .006). Lactate-pyruvate ratios and venous NTG concentrations were not significantly affected by NAC. Subsequently, another 20 consecutive patients were treated with intravenous NTG and continuously infused NAC (10 g/day). Seven remained pain free during the first 24 hr of NTG infusion; 11 required increments in NTG infusion rate for pain control. Acute myocardial infarction occurred in one patient, while none developed symptomatic hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)
Between Confidentiality and Scientific Exchange: The Place of Publication in Drug Discovery and Pharmaceutical Research
Authors: Martine Clozel
Journal: Science Translational Medicine (2011)

To continue to improve life expectancy and quality of life, the discovery of innovative therapies should be among the prime goals of the life sciences. The large majority of the drugs that are discovered and successfully developed to the point of being used by patients come from the drug industry, but publications from this sector are rare among life sciences research publications. Publications in the field of pharmaceutical drug discovery should take into account the confidentiality inherent to the protection of the intellectual property rights of a discovery, but they are fundamentally important because they can enhance scientific knowledge, improve the care and safety of patients, provide information for prescribers, and educate the public about the pharmaceutical industry.
Calcium-Independent Negative Inotropy by β-Myosin Heavy Chain Gene Transfer in Cardiac Myocytes
Authors: Todd J. Herron, Rene Vandenboom, Ekaterina Fomicheva, Lakshmi Mundada, Terri Edwards, Joseph M. Metzger
Journal: Circulation Research (2007)

Increased relative expression of the slow molecular motor of the heart (beta-myosin heavy chain [MyHC]) is well known to occur in many rodent models of cardiovascular disease and in human heart failure. The direct effect of increased relative beta-MyHC expression on intact cardiac myocyte contractility, however, is unclear. To determine the direct effects of increased relative beta-MyHC expression on cardiac contractility, we used acute genetic engineering with a recombinant adenoviral vector (AdMYH7) to genetically titrate beta-MyHC protein expression in isolated rodent ventricular cardiac myocytes that predominantly expressed alpha-MyHC (fast molecular motor). AdMYH7-directed beta-MyHC protein expression and sarcomeric incorporation was observed as soon as 1 day after gene transfer. Effects of beta-MyHC expression on myocyte contractility were determined in electrically paced single myocytes (0.2 Hz, 37 degrees C) by measuring sarcomere shortening and intracellular calcium cycling. Gene transfer-based replacement of alpha-MyHC with beta-MyHC attenuated contractility in a dose-dependent manner, whereas calcium transients were unaffected. For example, when beta-MyHC expression accounted for approximately 18% of the total sarcomeric myosin, the amplitude of sarcomere-length shortening (nanometers, nm) was depressed by 42% (151.0+/-10.7 [control] versus 87.0+/-5.4 nm [AdMYH7 transduced]); and genetic titration of beta-MyHC, leading to 38% beta-MyHC content, attenuated shortening by 57% (138.9+/-13.0 versus 59.7+/-7.1 nm). Maximal isometric cross-bridge cycling rate was also slower in AdMYH7-transduced myocytes. Results indicate that small increases of beta-MyHC expression (18%) have Ca2+ transient-independent physiologically relevant effects to decrease intact cardiac myocyte function. We conclude that beta-MyHC is a negative inotrope among the cardiac myofilament proteins.
Soluble Triggering Receptor Expressed on Myeloid cells-1 in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia
Authors: Guy J. Oudhuis, Judith Beuving, Dennis Bergmans, Ellen E. Stobberingh, Guul ten Velde, Catharina F. Linssen, Annelies Verbon
Journal: Intensive Care Medicine (2009)

Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) has proven to be a good biomarker for sepsis. For the diagnosis ventilator-associated pneumonia (VAP), however, there have only been a few, relatively small, studies on the role of this receptor. The aim of the study was to evaluate the usefulness of sTREM-1 in bronchoalveolar lavage fluid (BALF) from Intensive Care Unit patients as rapid diagnostic test for VAP.The concentration of sTREM-1 in 240 BALF samples was measured using a quantitative sandwich enzyme immunoassay. Two researchers who were blind to the assay results determined whether a VAP was present or not. Clinical suspicion of a VAP was confirmed by the presence of > or = 2% cells containing intracellular organisms and/or a quantitative culture result of > or = 10(4) colony forming units per millilitre BALF.The mean concentration of sTREM-1 was significantly higher in the BALF of patients with confirmed VAP than in that of patients without confirmed VAP. However, the area under the receiver-operating characteristic curve was 0.58 (95% confidence interval 0.50-0.65, P = 0.04).The results imply that the sTREM-1 assay in BALF may not be discriminative for VAP.
Localization of increased hepatic vascular resistance in liver cirrhosis
Authors: Yuro Shibayama, Katsuji Nakata
Journal: Hepatology (1985)

To determine the localization of increased vascular resistance in cirrhotic liver, blood pressures were measured by a direct cannulation method at several key points in the hepatic vascular pathway in normal and cirrhotic rats. Cirrhosis was produced by feeding a choline-deficient diet. Blood pressures in normal rats were 110 mm H2O in the portal vein, 68 mm H2O in the terminal portal venule, 28 mm H2O in the terminal hepatic venule and 20 mm H2O in the inferior vena cava. In cirrhotic rats, blood pressures in the portal vein and the terminal portal venule were 173 and 100 mm H2O, respectively, while those in the terminal hepatic venule and the inferior vena cava were elevated only slightly above normal. These hemodynamic data suggest that an increase in vascular resistance in cirrhotic liver is present in the intrahepatic portal vein and sinusoids, but not in intrahepatic hepatic vein. In cirrhotic liver, stenosis and distortion were found in peripheral branches of the portal vein, and sinusoidal stenoses and a decrease in sinusoidal space were recognized. Accordingly, it is suggested that the increase in vascular resistance in the intrahepatic portal vein and sinusoids correlate with these structural changes. Although severe stenoses and distortion were found in hepatic vein branches, it was thought that they do not contribute to portal hypertension because of lack of increase in vascular resistance in the intrahepatic hepatic vein.