tbuckley/cabot-search huggingface dataset:
Differences in Clinical Presentation, Management, and Outcomes of Acute Type A Aortic Dissection in Patients With and Without Previous Cardiac Surgery
Authors: J. Stewart Collins, Arturo Evangelista, Christoph A. Nienaber, Eduardo Bossone, Jianming Fang, Jeanna V. Cooper, Dean E. Smith, Patrick T. O’Gara, Truls Myrmel, Dan Gilon, Eric M. Isselbacher, Marc Penn, Linda A. Pape, Kim A. Eagle, Rajendra H. Mehta
Journal: Circulation (2004)

Background— There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD). Methods and Results— In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males ( P =0.02), older ( P =0.014), and to have a history of previous aortic dissection ( P &lt;0.001) or aneurysms ( P &lt;0.001). In contrast, PCS patients were less likely to have presenting chest pain ( P &lt;0.001). Cardiac tamponade was less common in PCS patients ( P =0.007). Fewer AAD patients with PCS underwent surgical repair ( P =0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death. Conclusions— Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients.
Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report
Authors: Michael E. Thase, Edward S. Friedman, Melanie M. Biggs, Stephen R. Wisniewski, Madhukar H. Trivedi, James F. Luther, Maurizio Fava, Andrew A. Nierenberg, Patrick J. McGrath, Diane Warden, George Niederehe, Steven D. Hollon, A. John Rush
Journal: American Journal of Psychiatry (2007)

Objective: The authors compared the effectiveness of cognitive therapy and pharmacotherapy as second-step strategies for outpatients with major depressive disorder who had received inadequate benefit from an initial trial of citalopram. Cognitive therapy was compared with medication augmentation and switch strategies. Method: An equipoise-stratified randomization strategy was used to assign participants to either augmentation of citalopram with cognitive therapy (N=65) or medication (N=117; either sustained-release bupropion [N=56] or buspirone [N=61]) or switch to cognitive therapy (N=36) or another antidepressant (N=86; sertraline [N=27], sustained-release bupropion [N=28], or extended-release venlafaxine [N=31]). Treatment outcomes and the frequency of adverse events were compared. Results: Less than one-third of participants consented to randomization strata that permitted comparison of cognitive therapy and pharmacotherapy. Among participants who were assigned to second-step treatment, those who received cognitive therapy (either alone or in combination with citalopram) had similar response and remission rates to those assigned to medication strategies. For those who continued on citalopram, medication augmentation resulted in significantly more rapid remission than augmentation with cognitive therapy. Among those who discontinued citalopram, there were no significant differences in outcome, although those who switched to a different antidepressant reported significantly more side effects than those who received cognitive therapy alone. Conclusions: After an unsatisfactory response to citalopram, patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant.
Airway neutrophils and interleukin-17
Authors: A. Linden, H. Hoshino, M Laan
Journal: European Respiratory Journal (2000)

It is well known that exacerbations of obstructive airways disease such as asthma and chronic obstructive pulmonary disease are associated with an increased number of neutrophils in the airways. However, the mechanisms behind this phenomenon are poorly understood. There is in vivo experimental evidence that the number of airway neutrophils is controlled by certain T-lymphocytes, but the mediators responsible for this lymphocyte-related neutrophilia have not yet been identified. In this review, novel evidence that the T-lymphocyte-related cytokine interleukin (IL)-17 can link the activation of certain T-lymphocytes to the recruitment and activation of airway neutrophils is described. The IL-17-induced neutrophil recruitment is mediated via induced CXC chemokine release through steroid-sensitive mechanisms and is modulated by release of endogenous tachykinins. These effects of IL-17 are potentiated by other pro-inflammatory cytokines such as (IL-1beta) and tumour necrosis factor-alpha. Clinical studies are needed to evaluate whether or not targeting these mechanisms can provide a useful pharmacotherapeutical approach against exaggerated mobilization of neutrophils in obstructive airways disease.
An unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica?
Authors: G.P.H. Lucker, R. Happle, P.M. Steijlen
Journal: British Journal of Dermatology (1995)

Journal Article An unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica? Get access G.P.H. Lucker, G.P.H. Lucker Department of Dermatology, University Hospital Nijmegen, PO Box 9191, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar R. Happle, R. Happle Department of Dermatology, University Hospital Marburg, Deutschhausstr. 9. 35033 Marburg, Germany Search for other works by this author on: Oxford Academic Google Scholar P.M. Steijlen P.M. Steijlen Department of Dermatology, University Hospital Nijmegen, PO Box 9191, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 1, 1 January 1995, Pages 150–151, https://doi.org/10.1111/j.1365-2133.1995.tb08643.x Published: 01 January 1995
Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case?control study
Authors: P. Gisondi, G. Tessari, A. Conti, S. Piaserico, S. Schianchi, A. Peserico, A. Giannetti, G. Girolomoni
Journal: British Journal of Dermatology (2007)

Psoriasis is a chronic inflammatory disease associated with an increased cardiovascular risk. Metabolic syndrome is a significant predictor of cardiovascular events.To investigate the prevalence of metabolic syndrome in patients with psoriasis.We performed a hospital-based case-control study on 338 adult patients with chronic plaque psoriasis and 334 patients with skin diseases other than psoriasis.Metabolic syndrome was significantly more common in psoriatic patients than in controls (30.1% vs. 20.6%, odds ratio 1.65, 95% confidence interval 1.16-2.35; P = 0.005) after the age of 40 years. Psoriatic patients also had a higher prevalence of hypertriglyceridaemia and abdominal obesity, whereas hyperglycaemia, arterial hypertension and high-density lipoprotein cholesterol plasma levels were similar. Although psoriasis patients were more frequently smokers, the association of psoriasis with metabolic syndrome was independent from smoking. There was no correlation between severity of psoriasis and prevalence of metabolic syndrome. Psoriatic patients with metabolic syndrome were older and had a longer disease duration compared with psoriatic patients without metabolic syndrome.Psoriatic patients have a higher prevalence of metabolic syndrome, which can favour cardiovascular events. We suggest psoriatic patients should be encouraged to correct aggressively their modifiable cardiovascular risk factors.
A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity
Authors: Stephen D. Gillies, Yan Lan, Thore Hettmann, Beatrice Brunkhorst, Yaping Sun, Stefan O. Mueller, Kin-Ming Lo
Journal: Clinical Cancer Research (2011)

The goal of the study was to engineer a form of interleukin 2 (IL-2) that, when delivered as a tumor-specific antibody fusion protein, retains the ability to stimulate an antitumor immune response via interaction with the high-affinity IL-2 receptor but has lower toxicity because of the reduced activation of the intermediate-affinity IL-2 receptor.We investigated changes in the proposed toxin motif of IL-2 by introducing a D20T mutation that has little effect on the activity of free IL-2. We expressed this IL-2 variant as a fusion protein with an antibody (NHS76) that targets the necrotic core of tumors and characterized this molecule (NHS-IL2LT) in vitro and in vivo.NHS-IL2LT was shown to have near normal biological activity in vitro by using T-cell lines expressing the high-affinity IL-2 receptor, but little or no activity by using cell lines expressing only the intermediate IL-2 receptor. Relative to the control antibody fusion protein containing wild-type IL-2, NHS-IL2LT retained antitumor activity against established neuroblastoma and non-small cell lung cancer metastases in syngeneic mouse tumor models but was much better tolerated in immune-competent mice and in cynomolgus monkeys.The qualities of low toxicity and single-agent efficacy shown suggest that NHS-IL2LT is a good candidate for therapeutic approaches combining standard cytotoxic and immune therapies. In fact, this molecule (also known as Selectikine or EMD 521873) is currently in phase I clinical trial.
R<scp>EGULATION OF</scp>E<scp>NZYMES OF THE</scp>U<scp>REA</scp>C<scp>YCLE AND</scp>A<scp>RGININE</scp>M<scp>ETABOLISM</scp>
Authors: Sidney M. Morris
Journal: Annual Review of Nutrition (2002)

▪ Abstract The urea cycle is comprised of five enzymes but also requires other enzymes and mitochondrial amino acid transporters to function fully. The complete urea cycle is expressed in liver and to a small degree also in enterocytes. However, highly regulated expression of several enzymes present in the urea cycle occurs also in many other tissues, where these enzymes are involved in synthesis of nitric oxide, polyamines, proline and glutamate. Glucagon, insulin, and glucocorticoids are major regulators of the expression of urea cycle enzymes in liver. In contrast, the “urea cycle” enzymes in nonhepatic cells are regulated by a wide range of pro- and antiinflammatory cytokines and other agents. Regulation of these enzymes is largely transcriptional in virtually all cell types. This review emphasizes recent information regarding roles and regulation of urea cycle and arginine metabolic enzymes in liver and other cell types.
Using cell replication data in mathematical modeling in carcinogenesis.
Authors: C J Portier, A Kopp-Schneider, C D Sherman
Journal: Environmental Health Perspectives (1993)

Risk estimation involves the application of quantitative models of dose versus response to carcinogenicity data. Recent advances in biology, computing, and mathematics have led to the application of mathematically complicated, mechanistically based models of carcinogenesis to the estimation of risks. This paper focuses on two aspects of this application, distinguishing between models using available data and the development of new models to keep pace with research developments.
Association between Body Composition and Frailty among Prevalent Hemodialysis Patients
Authors: Kirsten L. Johansen, Lorien S. Dalrymple, Cynthia Delgado, George A. Kaysen, John Kornak, Barbara Grimes, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2013)

Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.
Effects of Acute Increases in Left Ventricular Preload on Indices of Myocardial Function in Conscious, Unrestrained and Intact, Tranquilized Baboons
Authors: Michael Zimpfer, Stephen F. Vatner
Journal: Journal of Clinical Investigation (1981)

The effects of acute volume loading were examined on indices of left ventricular (LV) function in conscious, unrestrained and intact, tranquilized baboons. Experiments were conducted 1-3 mo after implantation of ultrasonic transducers to measure LV internal diameter and wall thickness, and miniature LV pressure gauges and aortic and left atrial catheters. In 10 intact, tranquilized baboons, rapid volume loading with saline increased LV end-diastolic pressure by 23.7±2.6 mm Hg, LV end-diastolic diameter by 7.8±1.5%, LV stroke work by 37.5±7.8%, while mean arterial pressure and peak LV wall stress did not change significantly. Despite the increase in preload and activation of the Frank-Starling mechanism, LV dP/dtmax and the maximum velocity of myocardial fiber shortening (LV dD/dtmax) did not change. Volume loading after β-adrenergic or combined β-adrenergic and cholinergic blockades or volume loading with blood instead of saline also failed to augment LV dP/dtmax and LV dD/dtmax despite the increase in preload. In order to volume load the baboons in the conscious state, a radiofrequency (RF) interrogator system was devised, which upon receipt of a radio command, activated a battery operated pump to infuse 1,000 ml of saline i.v. to the baboons. In these experiments, preload rose, i.e., LV end-diastolic diameter increased by 13.9±2.1% and the Frank-Starling mechanism could be demonstrated, i.e., stroke work rose by 42.8±7.4%, but LV dP/dtmax and LV dD/dtmax did not change. After preload was depressed by hemorrhage, the rapid infusion of either blood or saline increased LV dP/dtmax by 92.7±18.5% and LV dD/dtmax by 64.3±10.1%. Thus, acute volume loading in the conscious baboons increased LV end-diastolic size and even stroke work substantially. However, preload dependency of LV dP/dtmax and the maximum velocity of myocardial fiber shortening was only encountered at low levels of LV preload.
Muscle spasms associated with Sudeck's atrophy after injury.
Authors: C D Marsden, J A Obeso, M M Traub, J C Rothwell, H Kranz, F La Cruz
Journal: BMJ (1984)

Four patients developed abnormal involuntary movements of a limb after injury. All subsequently developed sympathetic algodystrophy with Sudeck9s atrophy and then abnormal muscle spasms or jerks of the affected limb, lasting years. Sympathetic block in three patients did not relieve the abnormal movements. Two patients obtained partial recovery spontaneously, but the other two required surgery for relief. The pathophysiology of this condition remains to be determined but the evidence suggests that it is a distinct, disabling clinical syndrome.
Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD
Authors: R. Buhl, L.J. Dunn, C. Disdier, C. Lassen, C. Amos, M. Henley, B. Kramer
Journal: European Respiratory Journal (2011)

Two, once daily ( q.d. ) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the β 2 -agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability. Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 μg q.d. (n=797) or tiotropium 18 μg q.d. (n=801) for 12 weeks. After 12 weeks, the two treatments had similar overall effects on “trough” (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01 versus 1.43; p&lt;0.001) and St George’s Respiratory Questionnaire (SGRQ) total score (least squares means 37.1 versus 39.2; p&lt;0.001; raw mean change from baseline -5.1 versus -3.0), and were significantly more likely to achieve clinically relevant improvements in these end-points (indacaterol versus tiotropium odds ratios of 1.49 for TDI and 1.43 for SGRQ, both p&lt;0.001). Adverse events were recorded for 39.7% and 37.2% of patients in the indacaterol and tiotropium treatment groups, respectively. The most frequent adverse events were COPD worsening, cough and nasopharyngitis. Both bronchodilators demonstrated spirometric efficacy. The two treatments were well tolerated with similar adverse event profiles. Compared with tiotropium, indacaterol provided significantly greater improvements in clinical outcomes.
Adaptive Modifications of Muscle Phenotype in High-Altitude Deer Mice Are Associated with Evolved Changes in Gene Regulation
Authors: Graham R. Scott, Todd S. Elogio, Mikaela A. Lui, Jay F. Storz, Zachary A. Cheviron
Journal: Molecular Biology and Evolution (2015)

At high-altitude, small mammals are faced with the energetic challenge of sustaining thermogenesis and aerobic exercise in spite of the reduced O2 availability. Under conditions of hypoxic cold stress, metabolic demands of shivering thermogenesis and locomotion may require enhancements in the oxidative capacity and O2 diffusion capacity of skeletal muscle to compensate for the diminished tissue O2 supply. We used common-garden experiments involving highland and lowland deer mice (Peromyscus maniculatus) to investigate the transcriptional underpinnings of genetically based population differences and plasticity in muscle phenotype. We tested highland and lowland mice that were sampled in their native environments as well as lab-raised F1 progeny of wild-caught mice. Experiments revealed that highland natives had consistently greater oxidative fiber density and capillarity in the gastrocnemius muscle. RNA sequencing analyses revealed population differences in transcript abundance for 68 genes that clustered into two discrete transcriptional modules, and a large suite of transcripts (589 genes) with plastic expression patterns that clustered into five modules. The expression of two transcriptional modules was correlated with the oxidative phenotype and capillarity of the muscle, and these phenotype-associated modules were enriched for genes involved in energy metabolism, muscle plasticity, vascular development, and cell stress response. Although most of the individual transcripts that were differentially expressed between populations were negatively correlated with muscle phenotype, several genes involved in energy metabolism (e.g., Ckmt1, Ehhadh, Acaa1a) and angiogenesis (Notch4) were more highly expressed in highlanders, and the regulators of mitochondrial biogenesis, PGC-1α (Ppargc1a) and mitochondrial transcription factor A (Tfam), were positively correlated with muscle oxidative phenotype. These results suggest that evolved population differences in the oxidative capacity and capillarity of skeletal muscle involved expression changes in a small suite of coregulated genes.
Dreaming and the brain: Toward a cognitive neuroscience of conscious states
Authors: J. Allan Hobson, Edward F. Pace-Schott, Robert Stickgold
Journal: Behavioral and Brain Sciences (2000)

Sleep researchers in different disciplines disagree about how fully dreaming can be explained in terms of brain physiology. Debate has focused on whether REM sleep dreaming is qualitatively different from nonREM (NREM) sleep and waking. A review of psychophysiological studies shows clear quantitative differences between REM and NREM mentation and between REM and waking mentation. Recent neuroimaging and neurophysiological studies also differentiate REM, NREM, and waking in features with phenomenological implications. Both evidence and theory suggest that there are isomorphisms between the phenomenology and the physiology of dreams. We present a three-dimensional model with specific examples from normally and abnormally changing conscious states.
Points from Letters: Women Doctors in the N.H.S
Authors: I. J. N. Sterling
Journal: BMJ (1975)

Ketoprofen, one of the many propionic acid derivatives flooding the market, is the subject of another substantial promotional programme only 12 months after the first. . ..Pharmaceutical companies, it seems, are playing into the hands of "Bennery" witlh such blatant "burning" of profits.. The public can hardly be expected to support the call for more money for the N.H.S. when it seems the medical profession is doing little to discourage such wasteful practices....
How the Neurocircuitry and Genetics of Fear Inhibition May Inform Our Understanding of PTSD
Authors: Tanja Jovanovic, Kerry J. Ressler
Journal: American Journal of Psychiatry (2010)

Exposure to traumatic events that produce extreme fear and horror is all too common in both military and civilian populations, but not all individuals develop posttraumatic stress disorder (PTSD) as a result of the exposure. What mediates risk and resilience in the development of PTSD and other stress-related psychopathology is of paramount importance to our further understanding of trauma-related psychopathology as well as the development of new treatment approaches. Biological factors, such as genotype and neurobiology, interact with environmental factors, such as childhood background and trauma load, to affect vulnerability and resilience in the aftermath of trauma exposure. One of the core symptoms of PTSD is the inability to control fear, which has led some investigators and clinicians to conceptualize PTSD as a disorder of fear or, more importantly, its inhibition. This review focuses on translational methods that have been used to examine fear conditioning and inhibition of fear in PTSD and summarizes genetic and neurobiological factors related to fear inhibition. The authors also discuss different pharmacological approaches that enhance fear inhibition and may improve treatment outcomes for patients with PTSD.