tbuckley/cabot-search huggingface dataset:
The Prevalence of Symptomatic Knee Osteoarthritis in China: Results From the China Health and Retirement Longitudinal Study
Authors: Xu Tang, Shengfeng Wang, Siyan Zhan, Jingbo Niu, Ke Tao, Yuqing Zhang, Jianhao Lin
Journal: Arthritis & Rheumatology (2015)

Objective To estimate the prevalence of symptomatic knee osteoarthritis (OA) in China. Methods Using data collected from the China Health and Retirement Longitudinal Study, a population‐based longitudinal survey conducted between 2011 and 2012, we estimated the prevalence of symptomatic knee OA according to sex, age, rural/urban area, socioeconomic status, and geographic region. Results Among 17,128 individuals (8,367 men and 8,761 women; mean age 59.8 years) included in the analysis, 8.1% had symptomatic knee OA. The prevalence of symptomatic knee OA was higher in women (10.3%) compared with men (5.7%) (adjusted odds ratio [OR] 1.88 [95% confidence interval 1.64–2.17]). The prevalence of symptomatic knee OA increased with age ( P for trend &lt;0.01). Symptomatic knee OA was more common in rural areas than in urban areas (OR 1.84 [95% confidence interval 1.46–2.31]). The prevalence of symptomatic knee OA was lower among individuals who had received more years of education and who lived in more developed areas ( P for trend &lt;0.01). The North and East regions of China had the lowest prevalence of symptomatic knee OA (5.4% and 5.5%, respectively), followed by the North‐East (7.0%), South‐Central (7.8%), and North‐West (10.8%) regions. The prevalence was highest (13.7%) in subjects living in the South‐West region. Conclusion Symptomatic knee OA in China was prevalent, and the prevalence varied according to sociodemographic, economic, and geographic factors. Epidemiologic studies identifying risk factors that contribute to variation in the prevalence of symptomatic knee OA in China are warranted.
Obsessive-Compulsive Disorder and Ventromedial Frontal Lesions: Clinical and Neuropsychological Findings
Authors: E Irle, C Exner, K Thielen, G Weniger, E Rüther
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors sought to determine the long-term outcome of subjects with severe and refractory obsessive-compulsive disorder (OCD) who had undergone ventromedial frontal leukotomy during the 1970s. Special emphasis was given to the analysis of specific lesion sites. METHOD: Sixteen OCD subjects who had undergone ventromedial frontal leukotomy were evaluated clinically and neuropsychologically and compared to seven well comparison OCD subjects without leukotomy. The 16 leukotomized subjects were divided into three groups according to the main lesion sites as determined by current magnetic resonance imaging scans. RESULTS: The leukotomized OCD subjects showed significant improvement of obsessive-compulsive symptoms; subjects with frontostriatal lesions tended to have improved most. The subjects with combined diagnoses of OCD and obsessive personality disorder (N=3) had improved significantly less. Of 11 subjects with lesions of the ventral striatum, eight had developed substance dependence postoperatively. Intellectual functions were largely preserved in subjects with ventromedial frontal lesions only or frontostriatal lesions. However, all subjects showed subnormal performance on the Wisconsin Card Sorting Test. Subjects with lesions of the dorsolateral frontal convexity also showed memory problems, attentional slowing, and lower performance IQ. CONCLUSIONS: Restricted ventromedial frontal leukotomy should be discussed as a last-resort treatment for severe and refractory OCD but not obsessive personality disorder. Lesions of the ventral striatum were significantly related to the occurrence of substance dependence, suggesting a role of this area in human addictive behavior. (Am J Psychiatry 1998; 155:255–263)
Why there is no legal or medical justification for the Saatchi bill
Authors: J. Raftery, C. Newdick
Journal: BMJ (2014)

More a memorial to deeply missed partner than a contribution to improving cancer care 

Consultation on the Medical Innovation (Saatchi) Bill attracted 18 000 responses, which are being analysed by the Department of Health.1 2 The health secretary, Jeremy Hunt, the prime minister, and several cabinet colleagues support the bill,3 which may become part of next year’s proposed legislation. Much medical opinion has been against the bill, but several eminent doctors and judges favour it.

The original bill was proposed by Maurice Saatchi, whose wife died from a rare form of ovarian cancer in 2011, aged 67. He believes her death was wasted because it did not help advance scientific understanding.

She does not seem to have been denied any specific treatment. Her cancer was “advanced, malignant and inoperable.” Saatchi described her radiotherapy and chemotherapy as “degrading and ineffective.”4 5 He believes that she received “standard treatment.” This is the target of the bill, which sees current law favouring it over innovative treatment. Commentary supporting the bill states: “Under present law, any deviation by a doctor from standard procedure is likely to result in a verdict of guilt …
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Harry Goldblatt, William B. Wartman
Journal: The Journal of Experimental Medicine (1937)

Section of the anterior spinal nerve roots from the sixth thoracic to the second lumbar inclusive did not prevent or significantly and permanently reduce hypertension produced by constricting the main renal arteries of dogs. The significance of these results for the pathogenesis of human and experimental hypertension is discussed.
ATRIAL NATRIURETIC PEPTIDE CONCENTRATIONS DURING PREGNANCY
Authors: A.A. Grace, V. D'Souza, R.K. Menon, S. O'Brien, P. Dandona, E.A.P. Steegers, P.R. Hein, E.A.M. Groeneveld, H.W. Jongsma, A.C.I.T.L. Tan, ThJ. Benraad
Journal: The Lancet (1987)
Mitochondrial metabolism revisited: a route to cardioprotection
Authors: A. Gonzalez-Loyola, I. Barba
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Inhibition of the malate–aspartate shuttle by pre-ischaemic aminooxyacetate loading of the heart induces cardioprotection’ by N.B. Stottrup et al. , pp. 257–266, this issue. 

Ischaemic preconditioning confers strong protection against myocardial ischaemia–reperfusion injury.1,2 Although its therapeutic application in the case of acute coronary syndromes is not possible in general, the cellular and molecular processes leading to preconditioning protection may be of interest for the designing of cardioprotective therapies.

Many cellular processes have been shown to be involved in preconditioning, including the stimulation of adenosine, bradykinin, and opioid membrane receptors,3 signalling cascades including PKCe and PKG,4,5 nitric oxide,6 and pro-survival kinases such as Akt.7 Mitochondria, a platform of cell signalling and a switch for cell death and survival, are generally regarded to play a key role in transmission and amplification of preconditioning signalling.8

It appears that many signalling processes involved in ischaemic preconditioning converge at the mitochondria.7,9 Stottrup et al. 10 show that by inhibiting the malate–aspartate shuttle …
Arousal and Nonarousal Enuretic Events
Authors: EDWARD R. RITVO, EDWARD M. ORNITZ, FRED GOTTLIEB, ALVIN F. POUSSAINT, BARRY J. MARON, KEITH S. DITMAN, KENNETH A. BLINN
Journal: American Journal of Psychiatry (1969)

Seven boys with primary enuresis were measured by 62 all-night EEGs, during which time 48 wets occurred. Imipramine was administered in a placebo, drug cross-over manner. Subjects with predominantly arousal enuresis showed increased evidence of neuroticism, a history of sporadic wetting, and no family history of enuresis. Subjects with predominantly nonarousal enuresis had minimal evidence of maladjustment, a history of regular wetting, family history of enuresis, and a better response to imipramine. The authors formulate a somatopsychic model for the etiology of enuresis, hypothesizing a pathophysiological substrate to explain the phenomenon.
Physical exercise and psychological well being: a critical review.
Authors: D Scully, J Kremer, M M Meade, R Graham, K Dudgeon
Journal: British Journal of Sports Medicine (1998)

The relation between physical exercise and psychological health has increasingly come under the spotlight over recent years. While the message emanating from physiological research has extolled the general advantages of exercise in terms of physical health, the equivalent psychological literature has revealed a more complex relation. The paper outlines the research evidence, focusing on the relation between physical exercise and depression, anxiety, stress responsivity, mood state, self esteem, premenstrual syndrome, and body image. Consideration is also given to the phenomena of exercise addiction and withdrawal, and implications for exercise prescription are discussed.
How Safe Should Drugs Be?
Authors: F. Gilbert McMahon
Journal: JAMA (1983)

ON AUG 18, 1982, a nationally televised morning news program featured a segment discussing the issue, "When the Food and Drug Administration approves a drug, does that mean it is safe?" Some three weeks later, the Commissioner of the FDA, Arthur Hull Hayes, MD, debated Sidney Wolfe, MD, of Ralph Nader's Health Research Group, on another nationally televised morning news program. Their debate concerned Dr Hayes' recent efforts to simplify and expedite some of the FDA's regulations concerning the investigation and approval of new drugs. Dr Wolfe wanted regulations tightened rather than relaxed, particularly in view of the necessity to recall such recently approved "unsafe drugs" such as benoxaprofen (Oraflex) and ticrynafen (Selacryn). Dr Wolfe's attack on the FDA's recent efforts to simplify some of its procedures is also an attack on the recent report of the Congressional Commission on the Federal Drug Approval Process. Twenty-six knowledgeable members representing academia,
Bile acids induce proliferation in hepatic stellate cells through the EGF receptor: Role of intracellular signaling pathways
Authors: G. Svegliati-Baroni, F. Ridolfi, M.H. Shoemaker, S. Saccomanno, M. Homan, P.L.M. Jansen, A. Benedetti, H. Moshage
Journal: Journal of Hepatology (2003)
Reciprocal Association of Plasma IGF-1 and Interleukin-6 Levels With Cardiometabolic Risk Factors in Nondiabetic Subjects
Authors: Elena Succurro, Francesco Andreozzi, Angela Sciaqua, Marta Letizia Hribal, Francesco Perticone, Giorgio Sesti
Journal: Diabetes Care (2008)

To examine the relationship between plasma IGF-1 and interleukin-6 (IL-6) levels in Caucasian nondiabetic subjects and evaluate the association of IGF-1 and IL-6 with the cardiometabolic risk factors characterizing metabolic syndrome (MetS).The study group consisted of 186 Caucasian nondiabetic subjects who underwent an oral glucose tolerance test and an euglycemic-hyperinsulinemic clamp. A logistic regression analysis, adjusted for age and sex, was used to determine the association between tertiles of IGF-1 and IL-6 and the MetS and its components.After adjusting for age and sex, both IGF-1 and IL-6 were correlated with insulin resistance and individual components of MetS, but in opposite directions. In the logistic regression model adjusted for age and sex, higher IL-6 and lower IGF-1 levels confer increased risk of having MetS and its two underlying pathophysiological abnormalities, i.e., visceral obesity and insulin resistance.The present results raise the possibility that lowered protection against inflammation, i.e., lower IGF-1 levels, may have a role in the development of MetS and its features, resulting in an imbalance between proinflammatory and anti-inflammatory proteins.
Slow recovery of excitability and the Wenckebach phenomenon in the single guinea pig ventricular myocyte.
Authors: M Delmar, D C Michaels, J Jalife
Journal: Circulation Research (1989)

The cellular mechanisms of Wenckebach periodicity were investigated in single, enzymatically dissociated guinea pig ventricular myocytes, as well as in computer reconstructions of transmembrane potential of the ventricular cell. When depolarizing current pulses of the appropriate magnitude were delivered repetitively to a well-polarized myocyte, rate-dependent activation failure was observed. Such behavior accurately mimicked the Wenckebach phenomenon in cardiac activation and was the consequence of variations in cell excitability during the diastolic phase of the cardiac cycle. The recovery of cell excitability during diastole was studied through the application of single test pulses of fixed amplitude and duration at variable delays with respect to a basic train of normal action potentials. The results show that recovery of excitability is a slow process that can greatly outlast action potential duration (i.e., postrepolarization refractoriness). Two distinct types of subthreshold responses were recorded when activation failure occurred: one was tetrodotoxin- and cobalt-insensitive (type 1) and the other was sensitive to sodium-channel blockade (type 2). Type 1 responses, which were commonly associated with the typical structure of the Wenckebach phenomenon (Mobitz type 1 block), were found to be the result of the nonlinear conductance properties of the inward rectifier current, IK1. Type 2 sodium-channel-mediated responses were associated with the so-called "millisecond Wenckebach." These responses may be implicated in the mechanism of Mobitz type 2 rate-dependent block. Single-cell voltage-clamp experiments suggest that variations in excitability during diastole are a consequence of the slow deactivation kinetics of the delayed rectifier, IK. Computer simulations of the ventricular cell response to depolarizing current pulses reproduced very closely all the response patterns obtained in the experimental preparation. It is concluded that postrepolarization refractoriness and Wenckebach periodicity are properties of normal cardiac excitable cells and can be explained in terms of the voltage dependence and slow kinetics of potassium outward currents. The conditions for the occurrence of intermittent activation failure during diastole will depend on the frequency and magnitude of the driving stimulus.
Preterm birth reduces the incidence of atopy in adulthood
Authors: Mirjami Siltanen, Karoliina Wehkalampi, Petteri Hovi, Johan G. Eriksson, Sonja Strang-Karlsson, Anna-Liisa Järvenpää, Sture Andersson, Eero Kajantie
Journal: Journal of Allergy and Clinical Immunology (2011)
Increased Activity of Nuclear Factor-κB Participates in Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis in Rats
Authors: Shiro Kitamoto, Kensuke Egashira, Chu Kataoka, Masamichi Koyanagi, Makoto Katoh, Hiroaki Shimokawa, Ryuichi Morishita, Yasufumi Kaneda, Katsuo Sueishi, Akira Takeshita
Journal: Circulation (2000)

Background —Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N ω -nitro- l -arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes [monocyte infiltration into coronary vessels, nuclear factor-κB (NF-κB) activation, and monocyte chemoattractant protein-1 expression] as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, no direct evidence for the importance of NF-κB in this process is known. Methods and Results —We examined the effect of a cis element decoy strategy to address the functional importance of NF-κB in the pathogenesis of cardiovascular remodeling. We found here that in vivo transfection of cis element decoy oligodeoxynucleotides against NF-κB to hearts prevented the L-NAME–induced early inflammation and subsequent coronary vascular medial thickening. In contrast, NF-κB decoy oligodeoxynucleotide transfection did not decrease the development of fibrosis, the expression of transforming growth factor-β 1 mRNA, or systolic pressure overload induced by L-NAME administration. Conclusions —The NF-κB system participates importantly in the development of early vascular inflammation and subsequent medial thickening but not in fibrogenesis in this model. The present study may provide a new aspect of how endothelium-derived NO contributes to anti-inflammatory and/or antiarteriosclerotic properties of the vascular endothelium in vivo.
Two stable levels of diastolic potential at physiological K+ concentrations in human ventricular myocardial cells.
Authors: J R McCullough, W T Chua, H H Rasmussen, R E Ten Eick, D H Singer
Journal: Circulation Research (1990)

Cells in many specimens of human ventricle can exhibit either of two stable levels of diastolic potential (DP) when exposed to 4 mM K+ in vitro (i.e., -78 +/- 4 mV or -45 +/- 5 mV, mean +/- SEM). In this report we show that the DP of some partially depolarized human ventricular cells developed a sustained 25-35 mV hyperpolarization (n = 28) when bath K+ concentration (K+b) was raised from 4 to 7 mM. On return of K+b to 4 mM, the DP of most, but not all, of these cells returned to the original depolarized levels. In other cells, the transition between the two levels of DP occurred at variable K+b ranging from 1 to 20 mM. We investigated the ionic mechanism(s) underlying the shifts between the two levels of potential by studying the K+ dependence of the DP in partially depolarized cells in 22 specimens of human ventricle. DP hyperpolarized an average of 25.6 mV (from -44.4 +/- 1.3 to -70.0 +/- 1.3 mV; n = 25) when K+b was increased from 4 to 7 mM. Intracellular K+ activity, determined by K+-selective microelectrodes, was within the range of normal reported for other mammalian species (106.7 +/- 4.4 mM in 4 mM K+; n = 22) and was unaffected by increasing K+b to 7 mM (111.7 +/- 6.6 mM; n = 6). Ba2+ (0.05 mM), a blocker of the inward rectifying K+ current, reversibly prevented the hyperpolarization, whereas acetylstrophanthidin (9 microM) failed to inhibit it. These results suggest that the hyperpolarization was due to a K+-dependent increase in K+ permeability and that electrogenic sodium pumping did not contribute significantly to the process. The ionic basis of the depolarization from a hyperpolarized level of DP also was investigated. Decreasing bath Na+ concentration and exposure to 30 microM tetrodotoxin did not prevent the depolarization. However, the depolarization could be inhibited by 2 mM Mn2+. These findings suggest that the depolarization may have been due to a Mn2+-sensitive inward current.
Bevacizumab-Induced Alterations in Vascular Permeability and Drug Delivery: A Novel Approach to Augment Regional Chemotherapy for In-Transit Melanoma
Authors: Ryan S. Turley, Andrew N. Fontanella, James C. Padussis, Hiroaki Toshimitsu, Yoshihiro Tokuhisa, Eugenia H. Cho, Gabi Hanna, Georgia M. Beasley, Christina K. Augustine, Mark W. Dewhirst, Douglas S. Tyler
Journal: Clinical Cancer Research (2012)

To investigate whether the systemically administered anti-VEGF monoclonal antibody bevacizumab could improve regional chemotherapy treatment of advanced extremity melanoma by enhancing delivery and tumor uptake of regionally infused melphalan (LPAM).After treatment with systemic bevacizumab or saline, changes in vascular permeability were determined by spectrophotometric analysis of tumors infused with Evan's blue dye. Changes in vascular structure and tumor hemoglobin-oxygen saturation HbO(2) were determined by intravital microscopy and diffuse reflectance spectroscopy, respectively. Rats bearing the low-VEGF secreting DM738 and the high-VEGF secreting DM443 melanoma xenografts underwent isolated limb infusion (ILI) with melphalan (LPAM) or saline via the femoral vessels. The effect of bevacizumab on terminal drug delivery was determined by immunohistochemical analysis of LPAM-DNA adducts in tumor tissues.Single-dose bevacizumab given three days before ILI with LPAM significantly decreased vascular permeability (50.3% in DM443, P < 0.01 and 35% in DM738, P < 0.01) and interstitial fluid pressure (57% in DM443, P < 0.01 and 50% in DM738, P = 0.01). HbO(2) decreased from baseline in mice following treatment with bevacizumab. Systemic bevacizumab significantly enhanced tumor response to ILI with LPAM in two melanoma xenografts, DM443 and DM738, increasing quadrupling time 37% and 113%, respectively (P = 0.03). Immunohistochemical analyses of tumor specimens showed that pretreatment with systemic bevacizumab markedly increased LPAM-DNA adduct formation.Systemic treatment with bevacizumab before regional chemotherapy increases delivery of LPAM to tumor cells and represents a novel way to augment response to regional therapy for advanced extremity melanoma.
Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage.
Authors: P R Galle, W J Hofmann, H Walczak, H Schaller, G Otto, W Stremmel, P H Krammer, L Runkel
Journal: The Journal of Experimental Medicine (1995)

Apoptosis occurs in the normal liver and in various forms of liver disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, and liver cells in animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system to investigate CD95-mediated apoptotic liver damage. Treatment of fresh human hepatocytes with low concentrations of agonistic antibodies against CD95 resulted in apoptosis of &amp;gt; 95% of the cultured liver cells within 4 and 7.5 h. Immunohistology of a panel of explanted liver tissues revealed that hepatocytes in normal livers (n = 5) and in alcoholic cirrhosis (n = 13) expressed low constitutive levels of CD95. CD95 receptor expression was highly elevated in hepatocytes in hepatitis B virus-related cirrhosis (n = 9) and in acute liver failure (n = 8). By in situ hybridization CD95 ligand messenger RNA expression was absent in normal liver but detected at high levels in livers with ongoing liver damage. In cases of hepatitis B virus-related cirrhosis and acute hepatic failure, ligand expression was found primarily in areas with lymphocytic infiltration. In contrast, in patients with alcoholic liver damage, high CD95 ligand messenger RNA expression was found in hepatocytes. These findings suggest that liver destruction in hepatitis B may primarily involve killing of hepatocytes by T lymphocytes using the CD95 receptor-ligand system. In alcoholic liver damage, death of hepatocytes might occur by fratricide and paracrine or autocrine mechanisms mediated by the hepatocytes themselves.