tbuckley/cabot-search huggingface dataset:
The Pharmacological Treatment of Pulmonary Arterial Hypertension
Authors: Lyn R. Frumkin
Journal: Pharmacological Reviews (2012)

Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease of various origins characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. The most common symptom at presentation is breathlessness, with impaired exercise capacity as a hallmark of the disease. Advances in understanding the pathobiology over the last 2 decades have led to therapies (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins or analogs) initially directed at reversing the pulmonary vasoconstriction and more recently directed toward reversing endothelial cell dysfunction and smooth muscle cell proliferation. Despite these advances, disease progression is common even with use of combination regimens targeting multiple mechanistic pathways. Overall 5-year survival for PAH has increased significantly from approximately 30% in the 1980s to approximately 60% at present, yet remains abysmal. This review summarizes the mechanisms of action, clinical data, and regulatory histories of approved PAH therapies and describes the latest agents in late-stage clinical development.
Ventricular Pressure-Volume Relationships and Oxygen Consumption in Fibrillation and Arrest
Authors: R. GRIER MONROE, GORDON FRENCH
Journal: Circulation Research (1960)

Pressure-volume relationships and myocardial oxygen consumption (V · O 2 ) were obtnined in an isolated heart during ventricular fibrillation, potassium-induced arrest, and isovolumetric contractions. The heart was found to be less distensible in fibrillation than in diastole or arrest. The V · O 2 increased from 4.6 to 14.6 cc./100 Gm. LV/min. as the fibrillating ventricle was distended. During arrest the V · O 2 remained constant despite ventricular distention. When the fibrillating ventricle was distended beyond a critical point coronary flow was compromised and the V · O 2 decreased. Beyond and only beyond this point could the V · O 2 be increased by the greater coronary flow induced by a higher perfusion pressure.
The Development and Application of Optogenetics
Authors: Lief Fenno, Ofer Yizhar, Karl Deisseroth
Journal: Annual Review of Neuroscience (2011)

Genetically encoded, single-component optogenetic tools have made a significant impact on neuroscience, enabling specific modulation of selected cells within complex neural tissues. As the optogenetic toolbox contents grow and diversify, the opportunities for neuroscience continue to grow. In this review, we outline the development of currently available single-component optogenetic tools and summarize the application of various optogenetic tools in diverse model organisms.
Strongyloidiasis and natural killer cell lymphocytosis
Authors: P. del Giudice
Journal: British Journal of Dermatology (2000)

Journal Article Strongyloidiasis and natural killer cell lymphocytosis Get access P. del Giudice P. del Giudice Infectious Diseases and Dermatology Unit, Hôpital Bonnet, 83600 Fréjus, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Page 1066, https://doi.org/10.1046/j.1365-2133.2000.03512.x Published: 01 May 2000
Lung mechanics in subjects showing increased residual volume without bronchial obstruction.
Authors: S Vulterini, M R Bianco, L Pellicciotti, A M Sidoti
Journal: Thorax (1980)

Fourteen subjects showing an increase of residual volume (RV) without any clinical or functional signs of bronchial obstruction were studied. Maximum expiratory flow volume (MEFV) curves were obtained with a pressure-corrected volume plethysmograph. Static pressure-volume curves were obtained by stepwise interruption of a slow expiration from total lung capacity (TLC) to RV. Static compliance was measured by the slope of pressure-volume curve between functional residual capacity (FRC) and FRC+20% of TLC. Maximum flow static recoil (MFSR) curves were constructed by plotting MEF obtained from MEFV curves against elastic pressure (Pst) obtained from pressure-volume curves at the same lung volumes. Most patients demonstrated a decrease of MEF 50% and 25% of VC. From the MFSR curves it was clear that this reduction was not the result of increased airways resistance, but rather of loss of elastic recoil. Most patients showed a significant decrease of Pst at different volumes and changes seem likely to be evidence of emphysema.
Persistent replication of the modified chimeric adenovirus ONYX-015 in both tumor and stromal cells from a patient with gall bladder carcinoma implants.
Authors: Scott Wadler, Bo Yu, Jian You Tan, Ron Kaleya, Alla Rozenblit, Della Makower, Morris Edelman, Maureen Lane, Elizabath Hyjek, Marshall Horwitz
Journal: Clinical Cancer Research (2003)

Purpose:  ONYX-015 is a chimeric, E1B-deleted adenovirus designed to replicatepreferentially in p53-deficient tumor cells; however, little is understood about its actual replication potential in human tumors. We hypothesized that replication of a late viral gene,  hexon , would demonstrate replication of virus in human tissues.   Experimental Design:  In the course of a clinical trial, a patient with paired abdominal wall implants from a primary gall bladder carcinoma was injected with ONYX-015, 1 × 10 10  viral particles/lesion, followed by sequential excision of the lesions at 37 h and 7 days. Tissue sections were analyzed for evidence of viral replication.   Results: In situ  Reverse transcription-PCR was used to measure expression of  hexon . Strong signals were obtained in gland-forming tumor cells both at 37 h and at 7 days. Signal was predominantly observed in the cytoplasm. The signal was also observed in adjacent normal stromal cells. Analysis of p53 status of the tumor by immunohistochemistry and Affymetrix Genechip demonstrated an inactivating mutation in p53. Routine H&E staining of the tumor sections revealed no evidence of necrosis at 37 h or 7 days after injection of virus. Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins.   Conclusions:  Evidence for replication of  hexon  confirms that ONYX-015 is not only present but capable of replicating in tumor cells up to 1 week after intralesional injection and that replication is not confined to p53-mutated tumor cells.
Evidence for Cure by Adjuvant Therapy in Colon Cancer: Observations Based on Individual Patient Data From 20,898 Patients on 18 Randomized Trials
Authors: Daniel Sargent, Alberto Sobrero, Axel Grothey, Michael J. O'Connell, Marc Buyse, Thierry Andre, Yan Zheng, Erin Green, Roberto Labianca, Chris O'Callaghan, Jean Francois Seitz, Guido Francini, Daniel Haller, Greg Yothers, Richard Goldberg, Aimery de Gramont
Journal: Journal of Clinical Oncology (2009)

Limited data are available on the time course of treatment failures (recurrence and/or death), the nature and duration of adjuvant treatment benefit, and long-term recurrence rates in patients with resected stage II and III colon cancer.
Effects of oral disopyramide phosphate on induction and sustenance of atrioventricular reentrant tachycardia incorporating retrograde accessory pathway conduction.
Authors: H C Kou, J S Hung, Y S Lee, D Wu
Journal: Circulation (1982)

We performed electrophysiologic studies before and after oral administration of disopyramide phosphate, 200 mg every 6 hours, in 20 patients with atrioventricular (AV) reentrant tachycardia using a retrogradely conducting accessory pathway. Disopyramide markedly depressed retrograde accessory pathway conduction by increasing the mean ventricular paced cycle length that produced ventriculoatrial block (less than or equal to 287 +/- 4 to greater than or equal to 392 +/- 22 msec, p less than 0.01); it also depressed antegrade normal pathway AV conduction by increasing the atrial paced cycle length that produced AV block (287 +/- 9 to 328 +/- 7 msec, p less than 0.01). In 14 patients, tachycardia could not be induced or sustained after disopyramide phosphate. In 13 patients, this reflected depression of the retrograde limb with either absence of atrial echoes (nine patients) or induction of nonsustained tachycardia that terminated after the QRS complex (four patients), and in one, it reflected depression of the antegrade limb with induction of a single atrial echo not followed by a QRS response. In six patients, sustained tachycardia could still be induced after disopyramide. Oral disopyramide phosphate is effective in preventing induction of sustained AV reentrant tachycardia in most patients. This effect is achieved by depression of the retrograde limb of the reentrant circuit.
Anti-Erythropoietin Antibodies and Pure Red Cell Aplasia
Authors: Jerome Rossert, Nicole Casadevall, Kai-Uwe Eckardt
Journal: Journal of the American Society of Nephrology (2004)

Eberhard Ritz More than twenty years ago, investigators who immunized rabbits against human erythropoietin (EPO) to generate polyclonal antibodies noted that the animals producing antibodies against this hormone became progressively anemic ([1][1]). Apparently human EPO was sufficiently different
Epigenetic Determinants of Resistance to Etoposide Regulation of Bcl-xL and Bax by Tumor Microenvironmental Factors
Authors: S T Taylor, J A Hickman, C Dive
Journal: JNCI Journal of the National Cancer Institute (2000)

BACKGROUND: Epigenetic factors (i.e., alterations of gene activity not involving mutations), as well as genetic changes in surviving cancer cells, may play an important role in drug resistance following cancer chemotherapy—a common cause of tumor relapse. Bcl-2 family proteins are central to the regulation of apoptotic cell death and modulate drug sensitivity. We investigated how survival signals in the cellular microenvironment affect the expression, protein conformation, and protein-protein interactions of the Bcl-2 family proteins Bax and Bcl-xL and how changes in response to microenvironmental signals alter the response of cancer cells to the drug etoposide. METHODS: JLP119 human B-lymphoma cells were treated with etoposide (40 μM) and then cultured in the presence of an activating anti-CD40 antibody, vascular cellular adhesion molecule-1 (VCAM-1)—to activate VLA-4 (α4β1) integrin, and interleukin 4. Cell fate was monitored after etoposide treatment with or without these microenvironmental signals. Bcl-xL gene transcription and protein levels of Bcl-xL and Bax were measured by northern and western blotting, respectively. Nuclear translocation of transcription factor NF-κB was monitored by immunofluorescence and inhibited by (E)-capsaicin. Bax conformation and Bax-Bcl-xL interactions were monitored by immunofluorescence and immunoprecipitation, respectively. RESULTS: Microenvironmental survival signals produced statistically significant reductions in etoposide-induced apoptotic cell death, from 84.6% (95% confidence interval [ CI] = 76.7%-92.4%) to 21.3% (95% CI = 19.5%-23.0%); P<.001. Activation of surface protein CD40 increased Bcl-xL protein levels via an (E)-capsaicin-inhibitable activation of NF-κB; i.e., (E)-capsaicin restored etoposide sensitivity. Interleukin 4 had no effect on Bcl-xL protein levels but accelerated the increase in Bcl-xL protein associated with CD40 activation. VCAM-1- and interleukin 4-mediated signals diminished conformational changes in Bax protein and prevented the etoposide-induced disruption of constitutive Bax-Bcl-xL binding. CONCLUSIONS: Microenvironmental factors reduce the sensitivity of a B-cell lymphoma to etoposide in vitro by modulating the expression and functions of Bax and Bcl-xL. This interaction may provide a paradigm for epigenetically induced drug resistance in other tumors.
Administration of antirheumatic drugs.
Authors: V Wright, R Hopkins
Journal: Annals of the Rheumatic Diseases (1976)

A study of 200 rheumatic patients attending an outpatient clinic and 72 general practitioners (GPs) was undertaken in relation to the administration of antirheumatic drugs. (1) Both patients and GPs agreed that effectiveness, absence of toxicity, and once daily administration were the important features of administration. (2) Significant differences between GPs and patients were noted in that patients more frequently preferred capsules than tablets. (3) GPs thought red was the best colour for an antirheumatic tablet, whereas patients thought white, this opinion being partly determined by the possible confusion of red tablets with sweets by children. (4) In a survey of 174 outpatients with rheumatic diseases, those with rheumatoid arthritis did not like blister packaging. A detailed assessment of 30 patients with rheumatoid arthritis in hospital confirmed this. Patients with moderate or severe rheumatoid disease of the hands often could not extract tablets from blister packs. Those who could found the packs difficult to open, the tablets broke, and came out suddenly, falling to the floor.
Lesson of the week: Managing patients with deliberate self harm who refuse treatment in the accident and emergency department
Authors: T B Hassan, A F MacNamara, A Davy, A Bing, G G Bodiwala
Journal: BMJ (1999)

Failure to assess adequately a patient's capacity to refuse treatment may have serious medicolegal consequences

Increasing numbers of patients attend the accident and emergency department after an episode of deliberate self harm,1 and an appreciable proportion of them refuse urgent medical treatment. Conflict may then arise between a doctor who considers a particular treatment vital and the patient who refuses to consent to it. The doctor has complex clinical, ethical, and medicolegal issues to consider. There are no published data on how doctors in accident and emergency departments in the United Kingdom currently manage these difficult cases. We used a case scenario and developed a questionnaire to investigate how doctors in accident and emergency departments in the Trent region would manage such a situation.

A scenario was constructed in which a woman who had taken a potentially life threatening drug overdose was brought to an accident and emergency department (box). A series of statements based on essential, decision making steps in her management was developed, and closed questions were used to determine what course of action doctors would take. The scenario and closed question interview style were designed to minimise any misinterpretation. Each of the four interviewers was given specific instructions on the use of the questionnaire and interview technique.

### Participants

All 14 accident and emergency departments in the Trent region with at least one consultant in accident and emergency medicine were identified from the 1996 directory of the British Association for Accident and Emergency Medicine.2 All doctors working in these departments were identified and contacted by telephone. The study was explained to them, and they were asked if they wished to take part. Arrangements were made to telephone at another more convenient time if necessary. Altogether 104 doctors were invited to participate, and all agreed to do so. …
Alveolar macrophages carbon load: a marker of exposure?
Authors: Ursula Ackermann-Liebrich
Journal: European Respiratory Journal (2012)

n December 2011, the Council of Europe adopted recommendations to prevent the most common chronic conditions in childhood, especially respiratory diseases in children, and ''invited the member states to tackle the problems that constitute the biggest risk factors that could trigger a chronic respiratory disease: tobacco smoke, poor indoor air quality, and outdoor air pollution'' [1].
Qualitative study of interpretation of reassurance among patients attending rheumatology clinics: "just a touch of arthritis, doctor?"
Authors: J. L Donovan
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To examine commonly used methods of reassurance by clinicians and explore their effect on patients. <b>Design:</b> Qualitative study of tape recordings of in-depth, semistructured interviews with patients before and after consultation and of their consultations with doctors. <b>Setting:</b> NHS specialist rheumatology clinics in two large British cities. <b>Participants:</b> 35 patients selected by consultant rheumatologists from general practitioner referral letters (28 women, 7 men; 24 with inflammatory arthropathies, 11 other rheumatological complaints). <b>Main outcome measures:</b> Patients9 perceptions of reassurance. <b>Results:</b> Reassurance was an important part of consultations, whether the diagnosis was clear or uncertain. Clinicians tried to reduce anxiety by emphasising the mildness, early stage, or non-seriousness of the disorder and the likelihood that patients would recover. Patients interpreted reassurance in the context of their own views and perceptions. Doctors9 emphasis on the mildness or earliness of the condition raised the spectre of future pain and disability rather than providing reassurance. Patients who felt that their problems were properly acknowledged felt more reassured. <b>Conclusions:</b> Typical patterns of reassurance were not successful because of the differences in perspective of patients and doctors. A key to successful reassurance seemed to be the doctor9s ability to acknowledge patients9 perspectives of their difficulties.
Tissue Kallikreins and Kinins: Regulation and Roles in Hypertensive and Diabetic Diseases
Authors: H S Margolius
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Gastric emptying of solid meals after truncal vagotomy and pyloroplasty in human subjects
Authors: D. J. Cowley, P. Vernon, T. Jones, H. I. Glass, A. G. Cox
Journal: Gut (1972)

Gastric emptying of isotopically labelled solid meals was studied in normal human subjects and in patients at different intervals after truncal vagotomy and Heineke-Mikulicz pyloroplasty. One to four weeks after vagotomy and pyloroplasty gastric emptying was delayed grossly in some patients regardless of the completeness of vagotomy. Patients with gross delay had symptoms of gastric retention. Eight weeks later emptying had returned towards normal and one or more years after vagotomy and pyloroplasty emptying was within the normal range.A subthreshold dose of carbachol injected during the course of emptying of a meal in some of the postvagotomy patients had no detectable influence on the rate of emptying of the meal.
Low Expression of Bax Predicts Poor Prognosis in Patients with Locally Advanced Esophageal Cancer Treated with Definitive Chemoradiotherapy
Authors: Seok Yun Kang, Jae Ho Han, Kwang Jae Lee, Jin-Hyuk Choi, Jung Il Park, Hyoung Il Kim, Hyun-Woo Lee, Jun Ho Jang, Joon Seong Park, Hugh Chul Kim, Seunghee Kang, Young Taek Oh, Mison Chun, Jang Hee Kim, Seung Soo Sheen, Ho-Yeong Lim
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. Experimental Design: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. Results: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P = 0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P = 0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P = 0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.
Physical activity of moderate intensity in leisure time and the risk of all cause mortality
Authors: J Bucksch
Journal: British Journal of Sports Medicine (2005)

There are conflicting data about the health benefits of moderately intense physical activity.To examine the effect of such activity on all cause mortality in a German sample of men and women.Physical activity during leisure time of 3742 men and 3445 women aged 30 to 69 was assessed in a baseline questionnaire from 1984 to 1986. The participants were observed during the follow up period until 1998 when a mortality follow up was conducted.During the follow up period, 300 women and 643 men had died. The multivariate rate ratios (RR) for the volume of lifestyle activities of moderate intensity (for example, gardening, walking, cycling) compared with sedentary lifestyle showed a clearly protective dose-response relation (p for trend <0.001) in women but not in men (p for trend 0.20). Following the recommendation for health enhancing physical activity a second analysis was conducted; 2.5 hours per week taking part in physical activity of moderate intensity decreased the relative risk of overall mortality (0.65 (95% confidence interval, 0.51 to 0.82) and 0.90 (0.77 to 1.01) for women and men, respectively).The volume of lifestyle activities of moderate intensity in leisure time was inversely associated with all cause mortality in women but not in men. With regard to the health enhancing physical activity recommendation as a threshold, there were favourable findings only in women.