tbuckley/cabot-search huggingface dataset:
Selective transplenic decompression of oesophageal varices by distal splenorenal and splenocaval shunt
Authors: R. A. Bhalerao, A. C. Pinto, R. D. Bapat, S. V. Shetty, P. D. Bhide, V. S. Waingankar, J. M. Kirtane, V. G. Mehendale, S. D. Shetty
Journal: Gut (1978)

The usefulness of selective transplenic decompression of oesophageal varices by distal splenorenal shunt and splenocaval shunt was evaluated in the control of gastrointestinal haemorrhage in patients with portal hypertension of varied aetiology. (Decompression was successful in 69 out of 78 cases.) It was shown that it is superior to total portosystemic shunts, as the incidence of encephalopathy was very low compared with the data from our series of portocaval shunts. The operative mortality has been progressively lowered and has now reached levels comparable with portocaval shunt. Distal splenorenal shunt when performed as an emergency procedure to arrest bleeding has limited usefulness but when performed as an elective or prophylactic procedure its results are comparable with those of portocaval shunt without the untoward complications such as encephalopathy. A modified selective decompression of varices has been described in which the distal end of the splenic vein is anastomosed to the inferior vena cava. Though no long term follow-up studies are available, we believe that this shunt is likely to prove superior to distal splenorenal shunt as it has both the advantages of the distal splenoral and the haemodynamic advantage of end-to-side portocaval shunt. We conclude that in patients with portal hypertension of varied aetiology, who have not had a haemorrhagic episode but in whom varices have been demonstrated or who have had one episode of haemorrhage from varices, the splenocaval shunt when feasible or the distal splenorenal shunt offers the optimal method of management at present in India.
CHEMOPREVENTION OF LUNG CANCER: The Rise and Demise of Beta-Carotene
Authors: Gilbert S. Omenn
Journal: Annual Review of Public Health (1998)

▪ Abstract Beta-carotene and retinoids were the most promising agents against common cancers when the National Cancer Institute mounted a substantial program of population-based trials in the early 1980s. Both major lung cancer chemoprevention trials not only showed no benefit, but had significant increases in lung cancer incidence and in cardiovascular and total mortality. A new generation of laboratory research has been stimulated. Rational public health recommendations at this time include: 1. Five-A-Day servings of fruits and vegetables, a doubling of current mean intake; 2. systematic investigation of the covariates of extremes of fruit and vegetable intake; 3. discouragement of beta-carotene supplement use, due to adverse effects in smokers and no evidence of benefit in non-smokers; 4. multilevel research to develop and evaluate candidate chemoprevention agents to prevent lung and other common cancers; and 5. continued priority for smoking prevention, smoking cessation, and avoidance of known carcinogens in the environment.
Myocyte Adaptation to Chronic Hypoxia and Development of Tolerance to Subsequent Acute Severe Hypoxia
Authors: Howard S. Silverman, Shao-kui Wei, Mark C. P. Haigney, Christopher J. Ocampo, Michael D. Stern
Journal: Circulation Research (1997)

Studies in animal models and humans suggest that myocardium may adapt to chronic or intermittent prolonged episodes of reduced coronary perfusion. Stable maintenance of partial flow reduction is difficult to achieve in experimental models; thus, in vitro cellular models may be useful for establishing the mechanisms of adaptation. Since moderate hypoxia is likely to be an important component of the low-flow state, isolated adult rat cardiac myocytes were exposed to 1% O2 for 48 hours to study chronic hypoxic adaptation. Hypoxic culture did not reduce cell viability relative to normoxic controls but did enhance glucose utilization and lactate production, which is consistent with an anaerobic pattern of metabolism. Lactate production remained transiently increased after restoration of normal O2 tension. Myocyte contractility was reduced (video-edge analysis), as was the amplitude of the intracellular Ca2+ transient (indo 1 fluorescence) in hypoxic cells. Relaxation was slowed and was accompanied by a slowed decay of the Ca2+ transient. These changes were not due to alterations in the action potential. Tolerance to subsequent acute severe hypoxia occurred in cells cultured in 1% O2 and was manifested as a delay in the time to full ATP-depletion rigor contracture during severe hypoxia and enhanced morphological recovery of myocytes at reoxygenation. The latter was still seen after normalization of the data for the prolonged time to rigor, suggesting a multifactorial basis for tolerance. An intervening period of normoxic exposure before subsequent acute severe hypoxia did not result in loss of tolerance but rather increased the delay to subsequent ATP depletion rigor. Cellular glycogen was preserved during chronic hypoxic exposure and increased after the restoration of normal O2 tension. As mitochondrial cytochromes should be fully oxygenated at levels well below 1% O2, hypoxic adaptation may be mediated by a low-affinity O2-sensing process. Thus, adaptations that occur during prolonged periods of moderate hypoxia are proposed to poise the myocyte in a better position to tolerate impending episodes of severe O2 deprivation.
On Fracture of the Metacarpal Bone of the Thumb
Authors: E. H. Bennett
Journal: BMJ (1886)

Teh "astragalo-scaphoid capsule" extends from the tip and sides of the i4ern&l malleolus across the astragalo-scaphoid articulation, on to the ,b2ternal cuneiform bone, and loses itself in a fibrous expansion,,'blending with ether ligambnts on the fore part of the inner border of the! foot.Tbheextent and direction of the fibres which chiefl7 oppose rec- tifietion iof the foot can be -felt with the fingbr-tip, whth traction isj mn4 on, the inverted foot.;A elirved tenotome sheild be'enteied im- mAiately,in front bf the anterior border of the internal malleohols the iWwle as far as possible being kept between'the ligaentato be divided 4U41 3t.hesuprjacent skin.In the next stage of the opeation, the blade is-t-be turned against the surface of the ligame4t, and, bl meansof a teitl sawibg motion, is made to divide it.iAi,thesuperfidial flbresate vlj1ed, d0eiNeroes cotre into play, and must u their tu ibe divided urtll ,bone is iiebaheL' By keeping the,knifs lose to the bones, and 4ireoting its&point towards the plantar aspect, the.caloan&-scaphoid igateut, 'hich 4forms an important part of the capsale: i these e4,se, c 'be easily divided.In this.operation, the' tendon of the pCPteiror tibial muscle will almost certainly be divided, and not im- probably that also of the anterior tibial muscle.Thellong and short
Evaluating the effects of asthma therapy on childhood growth: what can be learnt from the published literature?
Authors: J. Price, P. Hindmarsh, S. Hughes, J. Efthimiou
Journal: European Respiratory Journal (2002)

The difficulties of assessing the effects of asthma therapy on childhood growth were explored in the first part of this review. In this part of the review growth studies with inhaled corticosteroids were selected that included a control group, measured height by stadiometry and were of ≥1 yr duration. The studies were classified as type 1 (placebo control), type 2 (nonsteroidal therapy control), type 3 (comparator inhaled corticosteroid control) or type 4 (“real-life” studies with dose adjustment). The design attributes of these studies were then compared with the recommendations described in the first part of this review. Of the 18 studies identified, 17 were susceptible to one or more important confounding factors. Nevertheless, the outcomes of all 18 studies were mostly consistent. At recommended doses, beclomethasone dipropionate and budesonide demonstrated a small degree of growth suppression over 1–2 yrs (study types 1 and 2), but there was little evidence of such an effect with fluticasone propionate. Studies comparing different inhaled corticosteroids at recommended doses indicated more rapid growth with fluticasone propionate than with beclomethasone dipropionate or budesonide. However, none of the inhaled corticosteroids appeared to affect final height. In conclusion, the results from the majority of published growth studies with inhaled corticosteroids must be interpreted with a degree of caution owing to their potential susceptibility to important confounding factors. Further well-designed studies are needed to establish whether different inhaled corticosteroids have different effects on growth in the long term.
Sound and fury, signifying nothing
Authors: L. Farrell
Journal: BMJ (1996)

It is very hard to articulate just how disheartening the past week has been. Graham Greene reflected that anyone can die for something beautiful—a family, a civilisation, a truth—but that it takes a god to die for something miserable and sordid. As Ulster trudged towards its own squalid Calvary, we never needed a god more. As I explained in this column two months ago, the marching season is a time of atavistic madness and always a source of resentment and conflict, but none of us could have predicted such a rapid descent into a stinking chaos where monsters prowl and the wild packs …
Angiotensin-Converting Enzyme–Induced Activation of Local Angiotensin Signaling Is Required for Ascending Aortic Aneurysms in Fibulin-4–Deficient Mice
Authors: Jianbin Huang, Yoshito Yamashiro, Christina L. Papke, Yuichi Ikeda, Yanling Lin, Miteshkumar Patel, Tadashi Inagami, Victoria P. Le, Jessica E. Wagenseil, Hiromi Yanagisawa
Journal: Science Translational Medicine (2013)

Up-regulation of angiotensin-converting enzyme in the aortic wall causes aneurysms in fibulin-4–deficient mice, which can be prevented by losartan or captopril.
Primary Care Behavioral Interventions to Reduce Illicit Drug and Nonmedical Pharmaceutical Use in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer, Michael L. LeFevre, Albert L. Siu, James J. Peters, Linda Ciofu Baumann, Susan J. Curry, Mark H. Ebell, Francisco A.R. García, Jessica Herzstein, Douglas K. Owens, William R. Phillips, Michael P. Pignone, Adelita Gonzales Cantu, Wanda Nicholson
Journal: Annals of Internal Medicine (2014)

Update of the 2008 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for illicit drug use.The USPSTF reviewed the evidence on interventions to help adolescents who have never used drugs to remain abstinent and interventions to help adolescents who are using drugs but do not meet criteria for a substance use disorder to reduce or stop their use.This recommendation applies to children and adolescents younger than age 18 years who have not been diagnosed with a substance use disorder.The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care-based behavioral interventions to prevent or reduce illicit drug or nonmedical pharmaceutical use in children and adolescents. (I statement).
Identification of Differences in the Molecular Response to Vaccinia Virus in Atopic Dermatitis and Psoriasis Skin
Authors: D.N. Grigoryev, M.D. Howell, T. Watkins, Y. Chen, C. Cheadle, M. Boguniewicz, K.C. Barnes, D.Y. Leung
Journal: Journal of Allergy and Clinical Immunology (2009)
Transport of Molecules, Particles, and Cells in Solid Tumors
Authors: Rakesh K. Jain
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.
Rituximab versus oral cyclophosphamide for treatment of relapses of proliferative lupus nephritis: a clinical observational study
Authors: Gabriella Moroni, Beniamina Gallelli, Renato Alberto Sinico, Giulio Romano, Luigi Sinigaglia, Piergiorgio Messa
Journal: Annals of the Rheumatic Diseases (2012)

The clinical course of lupus nephritis is characterised by alternation of quiescences and exacerbations. The potential treatment strategies for renal flares are an important issue considering the potential toxicity and the incomplete efficacy of available drugs.1,–,4 Among the new agents for induction of remission, rituximab (RTX), an anti-CD20 monoclonal antibody, has emerged as a potential therapeutic alternative.5,–,8 In this prospective study, we report the first comparison between RTX and cyclophosphamide (CY) in the treatment of relapses of proliferative lupus nephritis (PLN). From April 2006 to January 2010, 24 patients with established PLN and a new renal relapse discontinued all immunosuppressive drugs and received one intravenous methylprednisolone pulse (MPP) (0.5–1 g each) for 3 days and, based on the patients' choice …
Study of the Biologic Effects of Lapatinib, a Reversible Inhibitor of ErbB1 and ErbB2 Tyrosine Kinases, on Tumor Growth and Survival Pathways in Patients With Advanced Malignancies
Authors: Neil L. Spector, Wenle Xia, Howard Burris, Herbert Hurwitz, E. Claire Dees, Afshin Dowlati, Bert O'Neil, Beth Overmoyer, Paul K. Marcom, Kimberly L. Blackwell, Deborah A. Smith, Kevin M. Koch, Andrew Stead, Steven Mangum, Matthew J. Ellis, Leihua Liu, Albert K. Man, Troy M. Bremer, Jennifer Harris, Sarah Bacus
Journal: Journal of Clinical Oncology (2005)

This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2-overexpressing solid malignancies.Heavily pretreated patients with metastatic cancers overexpressing ErbB2 and/or expressing ErbB1 were randomly assigned to one of five dose cohorts of lapatinib (GW572016) administered orally once daily continuously. The biologic effects of lapatinib on tumor growth and survival pathways were assessed in tumor biopsies obtained before and after 21 days of therapy. Clinical response was determined at 8 weeks.Sequential tumor biopsies from 33 patients were examined. Partial responses occurred in four patients with breast cancer, and disease stabilization occurred in 11 others with various malignancies. Responders exhibited variable levels of inhibition of p-ErbB1, p-ErbB2, p-Erk1/2, p-Akt, cyclin D1, and transforming growth factor alpha. Even some nonresponders demonstrated varying degrees of biomarker inhibition. Increased tumor cell apoptosis (TUNEL) occurred in patients with evidence of tumor regression but not in nonresponders (progressive disease). Clinical response was associated with a pretreatment TUNEL score > 0 and increased pretreatment expression of ErbB2, p-ErbB2, Erk1/2, p-Erk1/2, insulin-like growth factor receptor-1, p70 S6 kinase, and transforming growth factor alpha compared with nonresponders.Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB1 and/or ErbB2-overexpressing tumors. However, the limited sample size of this study and the variability of the biologic endpoints suggest that further work is needed to prioritize biomarkers for disease-directed studies, and underscores the need for improved trial design strategies in early clinical studies of targeted agents.
Compartmentation of Cyclic Nucleotide Signaling in the Heart
Authors: Rodolphe Fischmeister, Liliana R.V. Castro, Aniella Abi-Gerges, Francesca Rochais, Jonas Jurevičius, Jérôme Leroy, Grégoire Vandecasteele
Journal: Circulation Research (2006)

A current challenge in cellular signaling is to decipher the complex intracellular spatiotemporal organization that any given cell type has developed to discriminate among different external stimuli acting via a common signaling pathway. This obviously applies to cAMP and cGMP signaling in the heart, where these cyclic nucleotides determine the regulation of cardiac function by many hormones and neuromediators. Recent studies have identified cyclic nucleotide phosphodiesterases as key actors in limiting the spread of cAMP and cGMP, and in shaping and organizing intracellular signaling microdomains. With this new role, phosphodiesterases have been promoted from the rank of a housekeeping attendant to that of an executive officer.
SOME PSYCHOLOGICAL ASPECTS OF ISOLATED ANTARCTIC LIVING
Authors: CHARLES S. MULLIN
Journal: American Journal of Psychiatry (1960)

Some psychological effects of isolated group living in the Antarctic are described. It would appear that the cold, danger, and hardship are not major stresses. The most important psychological stresses appear to be: First, the problem of individual adjustment to the group; second, and more subtly acting, the relative "sameness" of the milieu; and third, the absence of certain accustomed sources of emotional satisfaction.
Precordial ST-segment depression during acute inferior myocardial infarction: clinical, scintigraphic and angiographic correlations.
Authors: R S Gibson, R S Crampton, D D Watson, G J Taylor, B A Carabello, N D Holt, G A Beller
Journal: Circulation (1982)

The cause and associated pathophysiology of precordial ST-segment depression (ST decreases) during acute inferior myocardial infarction (IMI) are controversial. To investigate this problem, electrocardiographic findings in 48 consecutive patients with acute IMI were prospectively compared with results of coronary angiography, submaximal exercise thallium-201 (201TI) scintigraphy and multigated blood pool imaging, all obtained 2 weeks after IMI, and with clinical follow-up at 3 months. Patients were classified according to the admission ECG obtained 3.3 +/- 3.1 hours after the onset of chest pain. Twenty-one patients (group A) had no or less than 1.0 mm ST decreases, and 27 (group B) had greater than or equal to 1.0 mm ST decreases in two or more precordial (V1-6) leads. Patients in group B had more prolonged chest pain after admission to the coronary care unit than those in group A (2.8 +/- 3.0 vs 1.2 +/- 1.1 hours, p less than 0.03), greater summed ST-segment elevation in leads II, III, aVF (6.7 +/- 4.7 vs 3.3 +/- 4.5 mm, p less than 0.02), higher plasma peak creatine kinase levels (1133 +/- 781 vs 653 +/- 482 IU/l, p less than 0.01), a higher prevalence of "true posterior" infarction by ECG criteria (26% vs 5%, p less than 0.05), a lower radionuclide ejection fraction (46 +/- 9% vs 54 +/- 6%, p less than 0.001), more extensive infarct-related asynergy (p less than 0.001) and 201TI perfusion abnormalities (p less than 0.01), more complications during hospitalization (p less than 0.03), and more cardiac events at 3 months (p less than 0.02). There were no significant differences between group A and group B in the extent of underlying coronary disease, prevalence of left anterior descending coronary artery disease, exercise-induced ST decreases or angina, and 201TI defects or wall motion abnormalities in anterior or septal segments. Thus, patients with acute IMI who have associated precordial ST decreases have greater global and regional left ventricular dysfunction due to more extensive inferior or inferoposterior wall infarction, rather than concomitant anteroseptal ischemic injury.
THE ROLE OF LIPOPROTEIN(a) IN ATHEROGENESIS AND THROMBOSIS
Authors: Katherine A. Hajjar, M.D, Ralph L. Nachman, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Lipoprotein(a) [Lp(a)] represents an important independent risk factor for atherosclerotic cardiovascular disease. Lp(a) constitutes a class of low-density lipoprotein-like particles that are structurally heterogenous due to variability within the distinguishing apoprotein, apolipoprotein(a) [Apo(a)]. Apo(a) bears a high degree of homology to the fibrinolytic zymogen, plasminogen, the parent molecule of the serine protease plasmin. Apo(a) contains a variable number of tandemly repeated triple-loop units called kringles, which appear to mediate Lp(a)'s interactions with fibrin and cell surface receptors. Although the mechanism of its atherogenicity is unknown, Lp(a) has been implicated in the delivery of cholesterol to the injured blood vessel, in blockade of plasmin generation on fibrin and cell surfaces, and as a stimulus for smooth muscle cell proliferation. In addition, new members of the plasminogen/Apo(a) gene family have been defined, creating a potential link between Lp(a) and the control of angiogenesis in both health and disease. Pharmacologic therapy of elevated Lp(a) levels has been only modestly successful; apheresis remains the most effective therapeutic modality.
Thyroid Hormone Targets Matrix Gla Protein Gene Associated With Vascular Smooth Muscle Calcification
Authors: Yoji Sato, Ryo Nakamura, Mitsutoshi Satoh, Kayoko Fujishita, Satoko Mori, Seiichi Ishida, Teruhide Yamaguchi, Kazuhide Inoue, Taku Nagao, Yasuo Ohno
Journal: Circulation Research (2005)

Thyroid hormones have marked cardiovascular effects in vivo. However, their direct effects on vascular smooth muscle cells have been unclear. Because thyroid hormones play critical roles in bone remodeling, we hypothesized that they are also associated with vascular smooth muscle calcification, one of the pathological features of vascular sclerosis. To test this hypothesis, we examined the effects of 3',3,5-triiodo-L-thyronine (T3) on the expression of calcification-associated genes in rat aortic smooth muscle cells (RAOSMCs). Quantitative RT-PCRs revealed that a physiological concentration of T3 (15 pmol/L free T3) increased mRNA level of matrix Gla protein (MGP), which acts as a potent inhibitor of vascular calcification in vivo, by 3-fold in RAOSMCs, as well as in cultured human coronary artery smooth muscle cells. In RAOSMCs transiently transfected with a luciferase reporter gene driven by the MGP promoter, T3 significantly stimulated luciferase activity. In addition, RNA interference against thyroid hormone receptor-alpha gene diminished the effect of T3 on MGP expression. Aortic smooth muscle tissues from methimazole-induced hypothyroid rats (400 mg/L drinking water; 4 weeks) also showed a 68% decrease in the MGP mRNA level, as well as a 33% increase in calcium content compared with that from the control euthyroid animals, whereas hyperthyroidism (0.2 mg T3/kg IP; 10 days) upregulated MGP mRNA by 4.5-fold and reduced calcium content by 11%. Our findings suggest that a physiological concentration of thyroid hormone directly facilitates MGP gene expression in smooth muscle cells via thyroid hormone nuclear receptors, leading to prevention of vascular calcification in vivo.