tbuckley/cabot-search huggingface dataset:
Acinar Structure in Symptom-free Adults by Helium-3 Magnetic Resonance
Authors: Barnaby Waters, John Owers-Bradley, Mike Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: The apparent diffusion coefficient of hyperpolarized 3He in the lungs has been shown to correlate directly in animal models with the peripheral airspace size and can detect changes in lung microstructure.Objectives: To study in vivo the 3He apparent diffusion coefficient and to demonstrate its sensitivity to changes in lung morphometry as a result of aging, exposure to cigarette smoke, and lung inflation.Methods: We assessed the variation in the diffusion of hyperpolarized 3He gas in the lungs by magnetic resonance techniques. Spirometric lung volumes were recorded.Measurements: We measured the dependence of 3He diffusion on age and on reported cigarette smoke exposure in 32 symptom-free adults. We also measured the dependence of the apparent diffusion coefficient on the degree of lung inflation.Results: In healthy never-smokers, the apparent diffusion coefficient increased with age from 0.115 to 0.155 cm2 · s−1 at 20 and 70 yr, respectively, increased linearly with lung inflation and was independent of individual's lung size after correcting for age. For active and passive smokers, the apparent diffusion coefficient increased by up to 40% compared with never-smokers with mean values significantly higher (p = 0.016 and p = 0.0007, respectively).Conclusions: Peripheral airspace size increases with age and after exposure to smoke in healthy adults in agreement with previous histologic studies. We have confirmed in vivo that peripheral airspace size is independent of intersubject lung size.
Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease
Authors: Matti Waterman, Wei Xu, Amreen Dinani, A Hillary Steinhart, Kenneth Croitoru, Geoffrey C Nguyen, Robin S McLeod, Gordon R Greenberg, Zane Cohen, Mark S Silverberg
Journal: Gut (2012)

<h3>Objective</h3> Previous investigations of short-term outcomes after preoperative exposure to biological therapy in inflammatory bowel disease (IBD) were conflicting. The authors aimed to assess postoperative outcomes in patients who underwent abdominal surgery with recent exposure to anti-tumour necrosis factor therapy. <h3>Design</h3> A retrospective case-control study with detailed matching was performed for subjects with IBD with and without exposure to biologics within 180 days of abdominal surgery. Postoperative outcomes were compared between the groups. <h3>Results</h3> 473 procedures were reviewed consisting of 195 patients with exposure to biologics and 278 matched controls. There were no significant differences in most postoperative outcomes such as: length of stay, fever (≥38.5°C), urinary tract infection, pneumonia, bacteraemia, readmission, reoperations and mortality. On univariate analysis, procedures on biologics had more wound infections compared with controls (19% vs 11%; p=0.008), but this was not significant in multivariate analysis. Concomitant therapy with biologics and thiopurines was associated with increased frequencies of urinary tract infections (p=0.0007) and wound infections (p=0.0045). Operations performed ≤14 days from last biologic dose had similar rates of infections and other outcomes when compared with those performed within 15–30 days or 31–180 days. Patients with detectable preoperative infliximab levels had similar rates of wound infection compared with those with undetectable levels (3/10 vs 0/9; p=0.21). <h3>Conclusion</h3> Preoperative treatment with TNF-α antagonists in patients with IBD is not associated with most early postoperative complications. A shorter time interval from last biological dose is not associated with increased postoperative complications. In most cases, surgery should not be delayed, and appropriate biological therapy may be continued perioperatively.
Cost-effectiveness of self-management in asthmatics: a 1-yr follow-up randomized, controlled trial
Authors: F. Gallefoss, P.S. Bakke
Journal: European Respiratory Journal (2001)

Patient education in asthma can improve outcome but cost-effectiveness has not been widely assessed. The aim of the present study was to carry out a cost-effectiveness analysis of patient education in asthmatics in a 12-month follow-up. The authors randomly allocated 78 asthmatics to a control or intervention group after they had received ordinary outpatient consultation care. Intervention consisted of two 2-h group sessions followed by 1–2 individual sessions administered by a nurse and a physiotherapist. Self-management was emphasized. Effectiveness was expressed in terms of quality of life and forced expiratory volume in one second (FEV 1 ). Doctor visits, days off work, dispensed pharmaceuticals, hospital admissions, travel costs, time costs and educational costs were recorded. The control and intervention groups induced mean total costs of Norwegian Krone (NOK) 16,000 and 10,500 per patient, respectively. A 10-unit improvement in St. George's Respiratory Questionnaire total score and a 5% improvement in FEV 1 in the intervention group were associated with a saving of NOK 3,400 and 4,500, respectively, compared to the control group. The number needed to educate (NNE) to make one person symptom free was associated with a saving of NOK 12,200. The results were robust to realistic changes in the assumptions upon which they were based. It could be concluded from this study that patient education in asthmatics in a 12-month follow-up improved patient outcomes and reduced costs.
Repeat Intracoronary Radiation for Recurrent In-Stent Restenosis in Patients Who Failed Intracoronary Radiation
Authors: Ron Waksman, Robert Lew, Andrew E. Ajani, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, Rosanna Chan, R. Larry White, William O. Suddath, Ellen Pinnow, Rebecca Torguson, Christian Dilcher, Roswitha Wolfram, Joseph Lindsay
Journal: Circulation (2003)

Intracoronary radiation therapy (IRT) is the only proven treatment for in-stent restenosis (ISR). It is, however, associated with a significant failure rate. The present study evaluated the outcomes of patients who underwent repeat intracoronary radiation for recurrent ISR.Fifty-one consecutive patients who failed a previous radiation treatment, presented with angina and angiographic evidence of ISR, and were treated with percutaneous coronary intervention (PCI) and repeat radiation to the same segment were studied. Twenty-five patients were treated with gamma radiation in a dose of 15 Gy, and 26 were treated with beta radiation doses of 18.3 to 23 Gy. The mean cumulative dose for this cohort was 39.5+/-11.9 Gy (range, 29 to 75.6 Gy). The outcomes of those patients were compared with outcomes of 299 patients who also failed initial radiation but were treated with repeat conventional PCI to a previously irradiated segment without repeat radiation. At 9 months after treatment, the repeat-IRT group had lower rates of target lesion revascularization (23.5% versus 54.6%; P<0.001) and major adverse cardiac events, including target vessel revascularization (29.4% versus 61.3%; P<0.001). At 9 months, patients with repeat IRT were free of angiographic and clinical events related to the radiation therapy.Repeat gamma or beta radiation to treat failed IRT for ISR after conventional PCI is safe and effective at 9 months and should be considered as a therapeutic option for this difficult patient subset.
A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma
Authors: Mark R. Gilbert, James J. Dignam, Terri S. Armstrong, Jeffrey S. Wefel, Deborah T. Blumenthal, Michael A. Vogelbaum, Howard Colman, Arnab Chakravarti, Stephanie Pugh, Minhee Won, Robert Jeraj, Paul D. Brown, Kurt A. Jaeckle, David Schiff, Volker W. Stieber, David G. Brachman, Maria Werner-Wasik, Ivo W. Tremont-Lukats, Erik P. Sulman, Kenneth D. Aldape, Walter J. Curran, Minesh P. Mehta
Journal: New England Journal of Medicine (2014)

Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known.
Psychostimulant Treatment and the Developing Cortex in Attention Deficit Hyperactivity Disorder
Authors: Philip Shaw, Wendy S. Sharp, Meaghan Morrison, Kristen Eckstrand, Deanna K. Greenstein, Liv S. Clasen, Alan C. Evans, Judith L. Rapoport
Journal: American Journal of Psychiatry (2008)

Objective: While there has been considerable concern over possible adverse effects of psychostimulants on brain development, this issue has not been examined in a prospective study. The authors sought to determine prospectively whether psychostimulant treatment for attention deficit hyperactivity disorder (ADHD) was associated with differences in the development of the cerebral cortex during adolescence. Method: Change in cortical thickness was estimated from two neuroanatomic MRI scans in 43 youths with ADHD. The mean age at the first scan was 12.5 years, and at the second scan, 16.4 years. Nineteen patients not treated with psychostimulants between the scans were compared with an age-matched group of 24 patients who were treated with psychostimulants. Further comparison was made against a template derived from 620 scans of 294 typically developing youths without ADHD. Results: Adolescents taking psychostimulants differed from those not taking psychostimulants in the rate of change of the cortical thickness in the right motor strip, the left middle/inferior frontal gyrus, and the right parieto-occipital region. The group difference was due to more rapid cortical thinning in the group not taking psychostimulants (mean cortical thinning of 0.16 mm/year [SD=0.17], compared with 0.03 mm/year [SD=0.11] in the group taking psychostimulants). Comparison against the typically developing cohort without ADHD showed that cortical thinning in the group not taking psychostimulants was in excess of age-appropriate rates. The treatment groups did not differ in clinical outcome, however. Conclusions: These findings show no evidence that psychostimulants were associated with slowing of overall growth of the cortical mantle.
Neurobiology of Feeding and Energy Expenditure
Authors: Qian Gao, Tamas L. Horvath
Journal: Annual Review of Neuroscience (2007)

Significant advancements have been made in the past century regarding the neuronal control of feeding behavior and energy expenditure. The effects and mechanisms of action of various peripheral metabolic signals on the brain have become clearer. Molecular and genetic tools for visualizing and manipulating individual components of brain homeostatic systems in combination with neuroanatomical, electrophysiological, behavioral, and pharmacological techniques have begun to elucidate the molecular and neuronal mechanisms of complex feeding behavior and energy expenditure. This review highlights some of these advancements that have led to the current understanding of the brain's involvement in the acute and chronic regulation of energy homeostasis.
Spironolactone as a Nonspecific Treatment for Primary Aldosteronism
Authors: EMMANUEL L. BRAVO, HARRIET P. DUSTAN, ROBERT C. TARAZI
Journal: Circulation (1973)

Studies were carried out in 14 patients with primary aldosteronism (1°A) to examine the mechanism(s) by which spironolactone reduces arterial pressure. Measures that produced salt and water depletion were found to consistently reduce arterial pressure. Plasma volume and arterial pressure correlated directly and significantly, r = +0.509 ( P &lt; 0.001), whether pressure was reduced by spironolactone alone or combined with either hydrochlorothiazide or low dietary sodium, or by rapid sodium depletion alone. With small doses of spironolactone, restricting or liberalizing dietary sodium was associated with decreases or increases, respectively, in arterial pressure and plasma volume. These results suggest 1) that the antihypertensive action of spironolactone is nonspecific and largely dependent on salt and water balance and 2) that maintenance of reduced plasma volume or extracellular fluid volume (ECFV) is a basic component of the pressure response of 1°A to spironolactone therapy.
Characterisation of post-pneumonectomy lung growth in adult mice
Authors: R. Voswinckel, V. Motejl, A. Fehrenbach, M. Wegmann, T. Mehling, H. Fehrenbach, W. Seeger
Journal: European Respiratory Journal (2004)

A model of inducible expansion of the gas exchange area in adult mice would be ideal for the investigation of molecular determinants of airspace regeneration in vivo . Therefore, the post-pneumonectomy (post-PNX) compensatory lung growth in adult C57BL/6 mice was characterised in this study. Mice underwent left-sided PNX. Right lung volume was assessed on days 1, 3, 5, 7, 10 and 21 after PNX, and total DNA and cellular proliferation of the right lung were determined. Lung histology was studied using immunohistochemistry and quantitatively characterised by detailed stereological investigations. Pulmonary function was assessed using a mouse body-plethysmograph. Following PNX, right-lung volume rapidly restored the initial volume of left and right lung. Total DNA increased significantly over 21 days and equalled the total DNA amount of both lungs in the control mice. Septal cell proliferation significantly increased after PNX, and included endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. Stereological investigations of left and right control lungs versus right lungs 21 days after PNX indicated complete restoration of body mass-specific alveolar surface area. Pulmonary function testing showed marked alteration at 3 days and normalisation at 21 days post-PNX. In conclusion, well reproducible reconstitution of alveolar gas-exchange surface based on septal tissue expansion may be provoked by pneumonectomy in adult mice.
Prenatal Expression Patterns of Genes Associated With Neuropsychiatric Disorders
Authors: Rebecca Birnbaum, Andrew E. Jaffe, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2014)

Objective Neurodevelopmental disorders presumably involve events that occur during brain development. The authors hypothesized that neuropsychiatric disorders considered to be developmental in etiology are associated with susceptibility genes that are relatively upregulated during fetal life (i.e., differentially expressed). Method The authors investigated the presence of prenatal expression enrichment of susceptibility genes systematically, as composite gene sets associated with six neuropsychiatric disorders in the microarray-based “BrainCloud” dorsolateral prefrontal cortex transcriptome. Results Using a fetal/postnatal log2-fold change threshold of 0.5, genes associated with syndromic neurodevelopmental disorders (N=31 genes, p=3.37×10–3), intellectual disability (N=88 genes, p=5.53×10–3), and autism spectrum disorder (N=242 genes, p=3.45×10–4) were relatively enriched in prenatal transcript abundance, compared with the overall transcriptome. Genes associated with schizophrenia by genome-wide association studies were not preferentially fetally expressed (N=106 genes, p=0.46), nor were genes associated with schizophrenia by exome sequencing (N=212 genes, p=0.21), but specific genes within copy-number variant regions associated with schizophrenia were relatively enriched in prenatal transcript abundance, and genes associated with schizophrenia by meta-analysis were functionally enriched for some neurodevelopmental processes. In contrast, genes associated with neurodegenerative disorders were significantly underexpressed during fetal life (N=46 genes, p=1.67×10–3). Conclusions The authors found evidence for relative prenatal enrichment of putative susceptibility genes for syndromic neurodevelopmental disorders, intellectual disability, and autism spectrum disorder. Future transcriptome-level association studies should evaluate regions other than the dorsolateral prefrontal cortex, at other time points, and incorporate further RNA sequencing analyses.
Chronic Inflammation and Impaired Coronary Vasoreactivity in Patients With Coronary Risk Factors
Authors: Thomas H. Schindler, Egbert U. Nitzsche, Manfred Olschewski, Nobuhisa Magosaki, Michael Mix, John O. Prior, Alvaro D. Facta, Ulrich Solzbach, Hanjoerg Just, Heinrich R. Schelbert
Journal: Circulation (2004)

The goal of this study was to examine a possible association between systemic microinflammation, as reflected by C-reactive protein (CRP) serum levels, and coronary vasomotion in patients with coronary risk factors but with angiographically normal coronary arteries.Coronary vasomotor function was studied in response to cold pressor testing (CPT) in 71 patients with normal angiograms. In all patients, CPT-induced changes in epicardial luminal area (LA; mm2) were assessed with quantitative angiography. Within 20 days, myocardial blood flow (MBF) responses to CPT were measured (mL x g(-1) x min(-1)) noninvasively with 13N-ammonia and PET imaging. The CPT-induced mean changes in LA and in MBF in patients with elevated CRP (> or =0.5 mg/dL) were significantly impaired compared with patients presenting with CRP levels within normal range (<0.5 mg/dL) (DeltaLA, -1.09+/-0.86 versus 0.45+/-0.63 mm2; DeltaMBF, 0.06+/-0.18 versus 0.44+/-0.31 mL x g(-1) x min(-1); P<0.0001, respectively). Coronary LA changes and MBF responses to CPT were inversely correlated with CRP serum levels (r=-0.84 and r=-0.63; P<0.0001). Lastly, regression analysis revealed a significant correlation between the changes in LA and MBF during CPT for patients with elevated CRP levels and those for patients with normal CRP levels (r=0.56 and r=0.66; P<0.001).These findings suggest a direct association between systemic microinflammation and altered coronary vasomotor function of both the epicardial conductance and the arteriolar resistance vessels.
On some Symptoms Produced by Tumours of the Optic Thalamus with a Case
Authors: J. M. Clarke
Journal: BMJ (1901)

OPTIO THALAMUS.[Nov. 9, It.bart, who is supposed to have flourished at the time of Frederick the Great, and who, in a well-known German students' ditty, gives a frightful account of his heroic exploits, of which the following-in very free translation, I am afraid- may give you an idea: At Potsdam I trepanned, just hear, Great Fred'rick's cook to him so dear.
p16INK4a Modulates p53 in Primary Human Mammary Epithelial Cells
Authors: Jianmin Zhang, Curtis R. Pickering, Charles R. Holst, Mona L. Gauthier, Thea D. Tlsty
Journal: Cancer Research (2006)

p16(INK4a) (p16) and p53 are tumor suppressor genes that are inactivated during carcinogenesis in many tumors. Here we show that p16 gene activity inversely modulates p53 status and function in primary human mammary epithelial cells. Reduced levels of p16 protein stabilize p53 protein through inhibition of proteolytic degradation, and this increase in p53 protein levels enhances the cellular response to radiation, represses proliferation, and transcriptionally activates downstream targets. Stabilization of p53 is mediated through the retinoblastoma/E2F/p14(ARF)/murine double minute-2 pathway. However, we have observed that p16 does not modulate p53 in fibroblasts, indicating a possible cell type-specific regulation of this pathway.
Increased risk of lichen simplex chronicus in people with anxiety disorder: a nationwide population-based retrospective cohort study
Authors: Y.-H. Liao, C.-C. Lin, P.-P. Tsai, W.-C. Shen, F.-C. Sung, C.-H. Kao
Journal: British Journal of Dermatology (2013)

The cingulate cortex is the main area in the brain involved in pruritus processing and is deactivated after scratching. Lichen simplex chronicus (LSC) is a common pruritic skin disorder characterized by skin lichenification following excessive scratching. Psychological factors may contribute to both the development and persistence of LSC.To estimate the hazard ratio (HR) of LSC in people with anxiety disorders compared with the general population.In this nationwide population-based retrospective cohort study we identified a total of 69 386 people, who formed the anxiety cohort, by using the Taiwan National Health Insurance Research Database from 2000 to 2009. The comparison cohort was composed of randomly selected people frequency matched for age (within 5-year intervals), sex and index date (the date of anxiety diagnosis) based on a 1 : 2 ratio. The risk of LSC was estimated as HRs and 95% confidence intervals (CIs) using the Cox proportional hazards model.After adjusting for age, sex and LSC-associated comorbidities, the people with anxiety had a 1·41-fold greater risk of developing LSC compared with the people in the comparison cohort (HR 1·41, 95% CI 1·30-1·52, P < 0·0001). In particular, individuals with obsessive-compulsive disorder had a significantly increased risk of developing LSC (HR 1·72, 95% CI 1·03-2·88, P = 0·0395).This study demonstrates that having an anxiety disorder is associated with an increased risk of LSC. Psychological factors were found to contribute to LSC. We recommend combining the management of LSC and psychological disorders to achieve favourable outcomes.
Phase I Study of Flavopiridol with Oxaliplatin and Fluorouracil/Leucovorin in Advanced Solid Tumors
Authors: Dana Rathkopf, Mark A. Dickson, Darren R. Feldman, Richard D. Carvajal, Manish A. Shah, Nian Wu, Robert Lefkowitz, Mithat Gonen, Lauren M. Cane, Heather J. Dials, Jennifer L. Winkelmann, George J. Bosl, Gary K. Schwartz
Journal: Clinical Cancer Research (2009)

Flavopiridol, a cyclin-dependent kinase inhibitor, has promising clinical activity when combined with chemotherapy. Preclinical data indicate that flavopiridol enhances oxaliplatin- and fluorouracil (5FU)-induced apoptosis in a sequence-dependent manner.We conducted a phase I trial of flavopiridol + FOLFOX (folinic acid, 5FU, and oxaliplatin) for advanced solid tumors. Flavopiridol was administered every 2 weeks with oxaliplatin before 5FU, based on sequence-dependent growth inhibition. Flavopiridol pharmacokinetics and p53 status were evaluated.Forty-eight patients were treated on study. With dose escalation of oxaliplatin (85 mg/m(2)) and 5FU (2,400 mg/m(2)), dose-limiting toxicities included hyponatremia, thrombocytopenia, and neutropenia. 5FU was subsequently reduced to allow for dose escalation of flavopiridol. Dose-limiting toxicities with escalation of flavopiridol were nausea, vomiting, and neutropenia. The maximum tolerated dose was 70 mg/m(2) flavopiridol, 85 mg/m(2) oxaliplatin, and 1,800 mg/m(2) 5FU continuous infusion over 48 hours. Clinical activity was noted in platinum-refractory germ cell tumors: 3 of 9 (33%) evaluable patients showed a partial response on imaging and 7 of 10 (70%) had a decline in serum tumor markers. Responses were also observed in pancreatic, gastric, and sweat gland tumors. Flavopiridol pharmacokinetics had significant interpatient variability. At the maximum tolerated dose, tumor samples were p53 mutant (>30% positive cells) for responders and p53 wild-type for nonresponders.Flavopiridol with FOLFOX is a safe and tolerable regimen. Promising clinical activity was seen across tumor types. Encouraging results in the platinum-refractory germ cell tumor population has prompted a phase II trial that is currently open for accrual.
Transvaginal NOTES hybrid cholecystectomy: feasibility results in 68 cases with mid-term follow-up
Authors: C. Zornig, H. Mofid, L. Siemssen, A. Emmermann, M. Alm, H.-A. von Waldenfels, C. Felixmüller
Journal: Endoscopy (2009)

Background and study aims: Natural orifice transluminal endoscopic surgery (NOTES) has been tested in the animal model for a multitude of procedures including cholecystectomy. Clinical experience using flexible endoscopes is, however, very limited. Transvaginal cholecystectomy has been shown to be the most feasible approach in which rigid instruments can be used. We report our experience in all patients treated over a 1-year period.