tbuckley/cabot-search huggingface dataset:
Thrombolytic treatment for acute ischaemic stroke: consent can be ethical
Authors: R. I Lindley
Journal: BMJ (1998)

According to proposed guidelines by Len Doyal it is unethical to randomise patients who are not competent to give informed consent in a randomised controlled trial when the treatment risks are not "minimalin relation to the standard available treatment."1 This would rule out trials of many forms of medical and surgical treatment for a wide range of disabling and life threatening conditions. Is it ethical to condemn millions of "mentallyincompetent" patients to no prospect of improving outcome? I believe a better guideline would be that such a trial is ethical if the treatment is promising but unproved provided that the potential risks are considered acceptable by the public. I illustrate my argument by discussing the role of thrombolytic treatment for acute ischaemic stroke. #### Summary points Recently suggested ethical guidelines would limit inclusion of mentally incompetent patients to trials of treatment that had only "minimalrisk" Some new treatments may have a substantial risk, but their potential for substantial benefit means that we should not exclude them from further evaluation The criterion of "minimalrisk" should be changed to "promisingbut unproved," provided that the public agrees that the risk is worth taking A new type of card, the randomised controlled trial card, may help educate the public about trials With proper safeguards, it is ethical to randomise mentally incompetent patients into further trials of thrombolytic treatment for acute ischaemic stroke The box shows the major requirements that I consider necessary for further randomised controlled trials of early thrombolytic treatment for acute ischaemic stroke. #### Criteria needed to justify trials of thrombolytic treatment for acute stroke
RGDV peptide selectively inhibits platelet-dependent thrombus formation in vivo. Studies using a baboon model.
Authors: Y Cadroy, R A Houghten, S R Hanson
Journal: Journal of Clinical Investigation (1989)

Since platelet hemostatic functions are mediated in part through the binding of adhesive proteins containing an RGD (Arg-Gly-Asp) recognition sequence, and since platelet reactions may be inhibited in vitro by RGD-containing peptides, we assessed in vivo the antithrombotic activity of RGDV (Arg-Gly-Asp-Val) tetrapeptide using a baboon thrombosis model. Thrombus formation was induced by a device consisting of a tubular segment coated with type I collagen, followed by two regions of expanded diameter exhibiting disturbed flow and stasis. The thrombogenic device was incorporated into femoral arteriovenous shunts under conditions of intermediate wall shear rate (100 s-1). Thrombus formation was measured by scintillation camera imaging of 111In-platelets and by counting of 125I-fibrinogen/fibrin. Thrombus that formed on the collagen substrate was rich in platelets, while thrombus formed in the disturbed flow regions was rich in fibrin and red cells. RGDV peptide was infused proximal to the thrombogenic device to maintain local plasma concentrations of 25, 50, and 100 microM. Infused RGDV decreased the accumulation of both platelets and fibrin on the collagen substrate in a dose-response manner. At the highest dose platelet and fibrin deposition after 40 min was reduced by greater than 80% (P less than 0.01). In the region of disturbed flow, RGDV (100 microM) reduced platelet deposition by 85% (P less than 0.01) but did not reduce the accumulation of fibrin (P less than 0.3). Similarly, the peptide inhibited the release of granular proteins from platelets associated with thrombus (platelet factor 4, beta-thromboglobulin; P less than 0.01), but did not prevent the appearance of fibrinopeptide A in circulating blood (P greater than 0.1). No systemic alterations in blood pressure, bleeding time, or platelet aggregation ex vivo were produced by locally infused RGDV. The antithrombotic effects of RGDV peptide disappeared within 5 min after discontinuing the infusion. In control studies infused RGEV (Arg-Gly-Glu-Val, 100 microM) showed no antithrombotic activity. Thus, RGDV selectively blocks platelet-dependent thrombus formation in vivo.
Preoperative Assessment of the Older Patient
Authors: Lawrence B. Oresanya, William L. Lyons, Emily Finlayson
Journal: JAMA (2014)

Surgery in older patients often poses risks of death, complications, and functional decline. Prior to surgery, evaluations of health-related priorities, realistic assessments of surgical risks, and individualized optimization strategies are essential.To review surgical decision making for older adult patients by 2 measures: defining treatment goals for elderly patients and reviewing the evidence relating risk factors to adverse outcomes. Assessment and optimization strategies for older surgical patients are proposed.A review of studies relating geriatric conditions such as functional and cognitive impairment, malnutrition, facility residence, and frailty to postoperative mortality and complications (including delirium, discharge to an institution, and functional decline). Medline, EMBASE, and Web of Science databases were searched for articles published between January 1, 2000, and December 31, 2013, that included patients older than 60 years.This review identified 54 studies of older patients; 28 that examined preoperative clinical features associated with mortality (n = 1,422,433 patients) and 26 that examined factors associated with surgical complications (n = 136,083 patients). There was substantial heterogeneity in study methods, measures, and outcomes. The absolute risk and risk ratios relating preoperative clinical conditions to mortality varied widely: 10% to 40% for cognitive impairment (adjusted hazard ratio [HR], 1.26 [95% CI, 1.06-1.49] to 5.77 [95% CI, 1.55-21.55]), 10% to 17% for malnutrition (adjusted odds ratio [OR], 0.88 [95% CI, 0.78-1.01] to 59.2 [95% CI, 3.6-982.9]), and 11% to 41% for institutionalization (adjusted OR, 1.5 [95% CI, 1.02-2.21] to 3.27 [95% CI, 2.81-3.81]).) Risk ratios for functional dependence relating to mortality ranged from an adjusted HR of 1.02 (95% CI, 0.99-1.04) to an adjusted OR of 18.7 (95% CI, 1.6-215.3) and for frailty relating to mortality, ranged from an adjusted HR of 1.10 (95% CI, 1.04-1.16) to an adjusted OR of 11.7 (95% CI not reported) (P < .001). Preoperative cognitive impairment (adjusted OR, 2.2; 95% CI, 1.4-2.7) was associated with postoperative delirium (adjusted OR, 17.0; 95% CI, 1.2-239.8; P < .05). Frailty was associated with a 3- to 13-fold increased risk of discharge to a facility (adjusted OR, 3.16 [95% CI, 1.0-9.99] to 13.02 [95% CI, 5.14-32.98]).Geriatric conditions may be associated with adverse surgical outcomes. A comprehensive evaluation of treatment goals and communication of realistic risk estimates are essential to guide individualized decision making.
In the Footsteps
Authors: Timothy J. Wolter
Journal: JAMA (1993)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Reproductive system in familial Mediterranean fever: an overview
Authors: E Ben-Chetrit
Journal: Annals of the Rheumatic Diseases (2003)

Familial Mediterranean fever (FMF), amyloidosis, and colchicine may affect the reproductive system of male and female patients. Colchicine treatment improves female fertility and the outcome of pregnancy and may prevent the development of amyloidosis. However, colchicine may induce oligospermia/azoospermia, but this effect is rare. Overall, colchicine treatment improves the prognosis of patients with FMF and increases their reproductive ability.
Absence of natural intracellular retinoids in mouse bone marrow cells and implications for PML-RARA transformation
Authors: H Niu, J Chacko, G Hadwiger, J S Welch
Journal: Blood Cancer Journal (2015)

The X-RARA fusion proteins have reduced sensitivity to all-trans-retinoic acid (ATRA), and have been proposed to act by decreasing retinoid-dependent transcription required for myeloid maturation.1, 2, 3 We therefore sought to determine whether maturing myeloid cells are exposed to natural retinoid ligands in vivo. Surprisingly, we detected a paucity of natural retinoids capable of transactivating RARA-dependent transcription in adult mouse bone marrow cells, and the trace activity we observed tended to be in erythroid-lineage cells, rather than in myeloid-progenitors. This suggests that the resistance to retinoid-mediated transactivation likely has a limited role in X-RARA-dependent leukemogenesis because natural retinoids are largely absent during normal myeloid maturation.
Assessing the Measure of a New Drug: Is Survival the Only Thing That Matters?
Authors: Daniel J. Sargent, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2008)

Clinical research to improve breast cancer treatment has produced multiple, meaningful advances in the last decade. New antiestrogen and chemotherapeutic agents—novel therapies directed towards HER2—such as trastuzumab and lapatinib, and antiangiogenic agents, such as bevacizumab, have all been added to the clinician’s armamentarium to treat metastatic disease. 1 Several of these advances have now demonstrated efficacy in the adjuvant setting, which raises the important question: What exactly has improved as these agents have been introduced into the metastatic setting? Given the current limited possibility of cure for these patients, there are two clinically important goals of treatment: make the patient live longer and delay or relieve symptoms. The first of these end points, codified as overall survival (OS), is simple to measure, unambiguous, and of unquestionable clinical relevance. However, symptom relief and palliation (or quality of life), despite recent progress, is notoriously difficult to measure. 2 Ideally, a newly introduced antineoplastic agent will demonstrate a significant and clinically meaningful prolongation of overall survival in the setting of a randomized controlled trial. However, the use of overall survival as the primary end point for a clinical trial has several major drawbacks. First, because mortality occurs after a relatively long time for most patients, statistically significant differences in OS require large numbers of patients and several years to reliably detect. For example, in a recently reported trial in which women with metastatic breast cancer were randomly assigned to receive either bevacizumab or no bevacizumab, in addition to first-line paclitaxel, the median survival for the trial population was not reached until nearly 8 years after the trial was opened, a full 2 years after initial results (based on an end point of progression-free survival [PFS]) were made public. 3 Second, for many new agents, patients assigned to the control arm are either allowed to cross over to the investigational agent or to receive the investigational agent off-study on disease progression. This strategy dilutes effects of an agent on OS, since patients in both arms will receive the new agent at some point. Although a prohibition of such cross-over is scientifically appealing, ethical considerations often preclude it, particularly if outcomes on earlier end points are found to be promising or the drug is approved in later line settings. Finally, for addition of a new agent, a prolongation of OS may be more difficult to detect now than in the past due to the beneficial effects of the many other antineoplastic therapies now available for breast cancer. 1
Tracheal stenosis, pulmonary agenesis, and patent ductus arteriosus
Authors: C. S. Nelson, I. K. R. Mc Millan, P. K. Bharucha
Journal: Thorax (1967)

Developmental anomalies ofthemajorpulmonary treearerare, butarenowrecognized morefrequently withimproved methods ofinvestigation. Theyareusually associated withother congenital defects affecting principally thecardiovascular, skeletal, andurogenital systems, butasanisolated lesion theyareveryrare. Defects ofthecardiovascular systemoccurmorecommonlywith pulmonary malformations, and theseinclude patent ductus arteriosus, septal defects, corbiloculare, andmaldevelopments oftheaortic archand itsgreat vessels. A caseofcongenital tracheal stenosis, unilateral agenesis ofthelung, andanassociated patent ductus arteriosus isdescribed together withthe management.
Respiratory Function and Portable Oxygen Therapy in Chronic Non-specific Lung Disease in Relation to Prognosis
Authors: J. E. Cotes
Journal: Thorax (1960)

Studies which relate prognosis in chronic lung disease to the results of assessment of lung function have usually been confined to a limited number of tests (Bates, Knott, and Christie, 1956; Platts and Greaves, 1957; Simpson, 1958).Such studies indicate which physiological tests have a prognostic value but provide limited information about their relative merits for prognosis.This information can only be obtained by the application to suitable subjects, both at rest and on exercise, of a number of tests which between them cover all aspects of respiratory function (cf., Baldwin, Cournand, and Richards, 1949; Gilson and Hugh-Jones, 1955).An analysis of this type is presented here.The data form part of an investigation into the ventilation changes between air and oxygen breathing on exercise in patients with chronic respiratory insufficiency.They fall into two groups: Series A, the three-and-a-half-year follow-up of 29 patients METHODS Each subject was studied at rest and while walking on a motor-driven treadmill which was adjusted so that he needed to stop on account of breathlessness after walking for approximately two minutes while breathing air.If he could double his walking time while breathing oxygen under these conditions he was considered to benefit from oxygen on exercise and to be a potential candidate for portable oxygen therapy; appropriate equipment (Cotes and Gilson, 1956b) was supplied on long-term loan if, in addition to being suitable, he found the equipment of assistance in the performance of everyday tasks.In addition to assessment of exercise ability, indices of ventilatory capacity, lung volume, pulmonary diflusing capacity, and alveolar ventilation and perfusion, includ- ing arterial blood gas tensions, were determined using the following method.
Pulsating Enophthalmos in Neurofibromatosis 1
Authors: Alexander Lehn, Caroline Airey, Richard Boyle
Journal: JAMA Neurology (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Activation of rat hepatic stellate cells leads to loss of glutathion S -transferases and their enzymatic activity against products of oxidative stress
Authors: Richard Whalen, Don C. Rockey, Scott L. Friedman, Thomas D. Boyer
Journal: Hepatology (1999)

Oxidative stress, mediated partly by lipid peroxidation products, may lead to increased collagen synthesis by hepatic stellate cells (HSC). Stellate cells are protected from oxidative stress by enzymes of detoxication such as the glutathione S-transferases (GSTs), which form glutathione conjugates with lipid peroxidation products (e.g., 4-hydroxy-2-nonenal [HNE]). To better understand the role of GSTs in stellate cell biology, we examined the expression and enzymatic activity of GSTs in normal and activated (both culture- and in vivo-activated) stellate cells. Normal stellate cells contained numerous isoforms of GST including those that detoxify HNE. High levels of enzymatic activity toward 1-chloro-2,4-dinitrobenzene (CDNB) and HNE were present in normal stellate cells and were similar to levels present in whole liver. Following activation by growth in culture, the expression of several GSTs (rGSTA1/A2, A3, and M1) was lost. Also, enzymatic activities toward CDNB and HNE fell approximately 90%. However, expression of rGSTP1 was maintained. A similar loss of rGSTA1/A2, A3, and M1 with persistent expression of rGSTP1 was present after activation in vivo. Furthermore, we identified 2 subpopulations of activated stellate cells with different GST phenotypes from injured livers. In summary, activated stellate cells lose most forms of GST and associated enzymatic activities that are present in normal stellate cells. The findings raise the possibility that activated stellate cells have less ability to detoxify lipid peroxidation products and may be susceptible to oxidative stress. Additionally, we propose that the phenotypic change in GSTs is a sensitive marker of stellate cell activation.
Induction of cytotoxic T-cell responses against immunoglobulin V region–derived peptides modified at human leukocyte antigen–A2 binding residues
Authors: Sabine Harig, Mathias Witzens, Angela M. Krackhardt, Andreas Trojan, Patrick Barrett, Ryan Broderick, A. Jason Zauls, John G. Gribben
Journal: Blood (2001)
Shear Stress Regulates Forward and Reverse Planar Cell Polarity of Vascular Endothelium In Vivo and In Vitro
Authors: Shannon McCue, Dorota Dajnowiec, Feng Xu, Ming Zhang, Moira R. Jackson, B. Lowell Langille
Journal: Circulation Research (2006)

Cultured vascular endothelium displays profound morphological adaptations to shear stress that include planar cell polarity (PCP) that is directed downstream. Endothelial cells in blood vessels are also polarized; however, the direction of polarity is vessel specific, and shear-independent mechanisms have been inferred. The regulation of endothelial PCP is therefore controversial. We report that the direction of PCP in blood vessels is age and vessel specific; nonetheless, it is caused by shear-related regulation of glycogen synthase kinase-3β (GSK-3β), a profound regulator of endothelial microtubule stability. When GSK-3β is inhibited, PCP reverses direction. Endothelium is the only cell type studied to date that can reverse direction of polarity. Tight regulation of GSK-3β, microtubule dynamics, and cell polarity was also required for the striking morphological responses of endothelium to shear stress (cell elongation and orientation with shear). Finally, the cytoskeletal polarity displayed in blood vessels is associated with polarized (shear-directed) cell mitoses that have important effects on endothelial repair. Vascular endothelium therefore displays a novel mode of mechanosensitive PCP that represents the first example of a single cell type that can reverse direction of polarity.
Lung Cancer Risk Reduction After Smoking Cessation: Observations From a Prospective Cohort of Women
Authors: J.O. Ebbert, P. Yang, C.M. Vachon, R.A. Vierkant, J.R. Cerhan, A.R. Folsom, T.A. Sellers
Journal: Journal of Clinical Oncology (2003)

We conducted this study because the duration of excess lung cancer risk among former smokers has been inconsistently reported, doubt has been raised regarding the population impact of smoking cessation, and differential risk reduction by histologic cell type after smoking cessation needs to be confirmed.The Iowa Women's Health Study is a prospective cohort study of 41,836 Iowa women aged 55 to 69 years. In 1986, mailed questionnaires were used to collect detailed smoking history. Age-adjusted lung cancer incidence through 1999 was analyzed according to years of smoking abstinence. Relative risks were estimated using Cox regression analysis.There were 37,078 women in the analytic cohort. Compared with the never smokers, former smokers had an elevated lung cancer risk (relative risk, 6.6; 95% confidence interval, 5.0 to 8.7) up to 30 years after smoking cessation for all former smokers. However, a beneficial effect of smoking cessation was observed among recent and distant former smokers. The risk of adenocarcinoma remained elevated up to 30 years for both former heavier and former lighter smokers.The risk for lung cancer is increased for both current and former smokers compared with never smokers and declines for former smokers with increasing duration of abstinence. The decline in excess lung cancer risk among former smokers is prolonged compared with other studies, especially for adenocarcinoma and for heavy smokers, suggesting that more emphasis should be placed on smoking prevention and lung cancer chemoprevention.
Activation of caspase-8 in transforming growth factor-?-induced apoptosis of human hepatoma cells
Authors: Yuka Shima, Kazuhiko Nakao, Tomoki Nakashima, Atsushi Kawakami, Keisuke Nakata, Keisuke Hamasaki, Yuji Kato, Katsumi Eguchi, Nobuko Ishii
Journal: Hepatology (1999)

Transforming growth factor-β1 (TGF-β1) has been shown to induce apoptosis in normal or transformed hepatocytes. To elucidate the biochemical pathways leading to apoptosis induced by TGF-β1 in human hepatoma cells (HuH-7), we examined the expression of Bcl-2-related proteins and X-chromosome-linked inhibitor of apoptosis (XIAP), and activation of the caspase cascade following TGF-β1 treatment. Bcl-xL expression began to decline at 12 hours after TGF-β1 treatment and progressively decreased to very low levels in a time-dependent manner. Bax expression showed a little change throughout the experiment. On the other hand, activation of caspase-8 was clearly observed at 36 hours after TGF-β1 treatment, followed by activation of caspase-9, and caspase-3 was activated at 48 hours after treatment at which time apoptosis of HuH-7 cells was observed. TGF-β1 significantly decreased XIAP expression in HuH-7 cells. Addition of an inhibitor of caspase-8 or caspase-3 (IETD-FMK or DEVD-CHO) markedly inhibited TGF-β1-induced apoptosis of HuH-7 cells. Fas/Fas ligand (FasL) interactions in HuH-7 cells were not involved in the apoptotic process. Furthermore, epidermal growth factor (EGF) also completely inhibited TGF-β1-induced apoptosis of HuH-7 cells by inhibiting activation of the caspase cascade. Our results suggested that activation of caspase-3 initiated through caspase-8 activation is involved in the apoptotic process induced by TGF-β1 in HuH-7 cells. Our results also showed that down-regulation of the expression of Bcl-xL and XIAP by TGF-β1 may facilitate activation of caspase-3 in these cells.