tbuckley/cabot-search huggingface dataset:
Phase II Study of Perifosine and Sorafenib Dual-Targeted Therapy in Patients with Relapsed or Refractory Lymphoproliferative Diseases
Authors: Anna Guidetti, Carmelo Carlo-Stella, Silvia L. Locatelli, Walter Malorni, Roberta Mortarini, Simonetta Viviani, Domenico Russo, Alfonso Marchianò, Roberto Sorasio, Anna Dodero, Lucia Farina, Laura Giordano, Massimo Di Nicola, Andrea Anichini, Paolo Corradini, Alessandro M. Gianni
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To evaluate safety and activity of perifosine and sorafenib combination therapy in patients with lymphoproliferative diseases. Experimental Design: Patients with relapsed and refractory lymphoproliferative diseases received perifosine (50 mg twice daily) for 1 month. Patients achieving less than partial response (PR) after perifosine alone were administered the combination therapy [perifosine plus sorafenib (400 mg twice daily)] until progressive disease (PD) or unacceptable toxicity occurred. The pERK and pAKT in peripheral blood lymphocytes as well as serum cytokine levels were investigated as predictive biomarkers of response. Results: Forty patients enrolled in this study. After 1 month of perifosine alone, 36 who achieved less than PR went on to combination therapy, whereas four patients with chronic lymphocytic leukemia (CLL) who achieved PR continued with perifosine alone for a median of 10 months (range, 4–21). The most common drug-related toxicities were grade 1–2 anemia (17%), thrombocytopenia (9%), diarrhea (25%), joint pain (22%), and hand–foot skin reaction (25%). Three patients experienced grade 3 pneumonitis. Eight patients (22%) achieved PR, 15 (42%) achieved stable disease, and 13 (36%) experienced PD. A 28% PR rate was recorded for 25 patients with Hodgkin lymphoma. Among all patients, median overall survival and progression-free survival were 16 and 5 months, respectively. Early reductions in pERK and pAKT significantly correlated with the probability of clinical response. Conclusions: Perifosine and sorafenib combination therapy is feasible with manageable toxicity and demonstrates promising activity in patients with Hodgkin lymphoma. The predictive value of pERK and pAKT should be confirmed in a larger patient cohort. Clin Cancer Res; 20(22); 5641–51. ©2014 AACR.
Adenosine increases potassium conductance in isolated rabbit atrioventricular nodal myocytes
Authors: A.E. Martynyuk, K.A. Kane, S.M. Cobbe, A.C. Rankin
Journal: Cardiovascular Research (1995)

Objective: To study the actions of adenosine on the electrophysiology of spontaneously active, rod-shaped cells enzymatically isolated from rabbit atrioventricular (AV) node. Methods: Calcium-tolerant myocytes were isolated from the region of the AV node by enzymatic and mechanical dispersion. They were rod- or spindle-shaped, with spontaneous activity at 35–37 °C, and had higher membrane resistances (776 ± 283 MΩ, n = 13), compared to atrial cells (41 ± 18.2 MΩ, n = 7; P < 0.001). Membrane potential, spontaneous action potentials and transmembrane ionic currents were studied using the whole-cell patch-clamp technique, in current-clamp and voltage-clamp mode. Results: Adenosine (0.1–50 μM) slowed or abolished the spontaneous activity, with hyperpolarisation of the membrane potential. Voltage-clamp experiments showed that adenosine induced an inwardly rectifying time-independent current. The adenosine-induced current was shown to be carried by potassium ions by the effect of increasing external potassium, which altered the reversal potential in accordance with the calculated potassium equilibrium potential. The A1 adenosine receptor antagonist, CPDPX (8-cyclopentyl-1,3-dypropylxanthine), reversed the effects of adenosine and an A1 receptor agonist, R-PIA [R(−)N6-(2-phenylisopropyl)adenosine] had effects similar to adenosine. Adenosine also caused a small decrease in inward calcium current (ICa) in some AV nodal cells. Conclusions: These results indicate that adenosine acts at A1 adenosine receptors to suppress spontaneous activity, hyperpolarise membrane potential and induce a time-independent potassium current in AV nodal cells. These actions, combined with reduction in inward calcium current in some cells, may underlie the negative chronotropic and dromotropic actions of adenosine on rabbit AV nodal cells.
The Tumor Suppressor Smad4 Is Required for Transforming Growth Factor β–Induced Epithelial to Mesenchymal Transition and Bone Metastasis of Breast Cancer Cells
Authors: Martine Deckers, Maarten van Dinther, Jeroen Buijs, Ivo Que, Clemens Löwik, Gabri van der Pluijm, Peter ten Dijke
Journal: Cancer Research (2006)

Abstract Transforming growth factor β (TGF-β) can act as suppressor and promoter of cancer progression. Intracellular Smad proteins (i.e., receptor regulated Smads and common mediator Smad4) play a pivotal role in mediating antimitogenic and proapoptotic effects of TGF-β, but their function in TGF-β-induced invasion and metastasis is unclear. Here, we have investigated the role of Smad4 in a cellular and mouse model for TGF-β-induced breast cancer progression. Consistent with its tumor suppressor function, specific silencing of Smad4 in NMuMG mammary gland epithelial cells using small hairpin RNA (shRNA)–expressing RNAi vectors strongly mitigated TGF-β-induced growth inhibition and apoptosis. Smad4 knockdown also potently inhibited TGF-β-induced epithelial to mesenchymal transition of NMuMG cells as measured by morphologic transformation from epithelial to fibroblast-like cells, formation of stress fibers, inhibition of E-cadherin expression, and gain of expression of various mesenchymal markers. Furthermore, we show that knockdown of Smad4 in MDA-MB-231 breast cancer cells strongly inhibited the frequency of bone metastasis in nude mice by 75% and significantly increased metastasis-free survival. Communication of MDA-MB-231 cells with the bone microenvironment, which is needed for optimal tumor cell growth and metastasis, may be affected in Smad4 knockdown cells as TGF-β-induced expression of interleukin 11 was attenuated on Smad4 knockdown. Taken together, our results show that Smad4 plays an important role in both tumor suppression and progression of breast cancer cells. (Cancer Res 2006; 66(4): 2202-9)
Atrial Septal Aneurysm in Adult Patients
Authors: Andreas Mügge, Werner G. Daniel, Christiane Angermann, Christoph Spes, Bijoy K. Khandheria, Itzhak Kronzon, Robin S. Freedberg, Andre Keren, Karl Dennig, Rolf Engberding, George R. Sutherland, Zvi Vered, Raimund Erbel, Cees A. Visser, Oliver Lindert, Dirk Hausmann, Paul Wenzlaff
Journal: Circulation (1995)

Background An atrial septal aneurysm (ASA) is a well-recognized abnormality of uncertain clinical relevance. We reevaluated the clinical significance of ASA in a large series of patients. The aims of the study were to define morphological characteristics of ASA by transesophageal echocardiography (TEE), to define the incidence of ASA-associated abnormalities, and to investigate whether certain morphological characteristics of ASA are different in patients with and without previous events compatible with cardiogenic embolism. Methods and Results Patients with ASA were enrolled from 11 centers between May 1989 and October 1993. All patients had to undergo transthoracic and transesophageal echocardiography within 24 hours of each other; ASA was defined as a protrusion of the aneurysm &gt;10 mm beyond the plane of the atrial septum as measured by TEE. Patients with mitral stenosis or prosthesis or after cardiothoracic surgery involving the atrial septum were excluded. Based on these criteria, 195 patients 54.6±16.0 years old (mean±SD) were included in this study. Whereas TEE could visualize the region of the atrial septum and therefore diagnose ASA in all patients, ASA defined by TEE was missed by transthoracic echocardiography in 92 patients (47%). As judged from TEE, ASA involved the entire septum in 100 patients (51%) and was limited to the fossa ovalis in 95 (49%). ASA was an isolated structural defect in 62 patients (32%). In 106 patients (54%), ASA was associated with interatrial shunting (atrial septal defect, n=38; patent foramen ovale, n=65; sinus venosus defect, n=3). In only 2 patients (1%), thrombi attached to the region of the ASA were noted. Prior clinical events compatible with cardiogenic embolism were associated with 87 patients (44%) with ASA; in 21 patients (24%) with prior presumed cardiogenic embolism, no other potential cardiac sources of embolism were present. Length of ASA, extent of bulging, and incidence of spontaneous oscillations were similar in patients with and without previous cardiogenic embolism; however, associated abnormalities such as atrial shunts were significantly more frequent in patients with possible embolism. Conclusions As shown previously, TEE is superior to the transthoracic approach in the diagnosis of ASA. The most common abnormalities associated with ASA are interatrial shunts, in particular patent foramen ovale. In this retrospective study, patients with ASA (especially with shunts) showed a high frequency of previous clinical events compatible with cardiogenic embolism; in a significant subgroup of patients, ASA appears to be the only source of embolism, as judged by TEE. Our data are consistent with the view that ASA is a risk factor for cardiogenic embolism, but thrombi attached to ASA as detected by TEE are apparently rare.
CRITIQUE OF MACROSCOPIC EXAMINATION OF SPECIMENS REMOVED IN THIRTY-TWO CONSECUTIVE LAPAROTOMIES.
Authors: F. BYRON ROBINSON
Journal: JAMA (1894)

(Continued from page 46). <i>Case 9</i>.—Age 24. Puberty at 11; menstruation regular but quite profuse, lasting about seven days. She was very pale and anemic. Menstruation was very painful for four days and compelled her to be in bed two days. Last period flowed for two weeks. Has long had leucorrhea which has distinct odor and is yellow. She is tender on pressure in pelvis, especially on left side. She was occasionally sick in bed for two months at a time and had so much pain that much morphin was used. Two years ago she had two abortions and since that time she has been ill with pelvic trouble. I sent her to the Woman's Hospital and under rest and hot douches the exudates (size of a large apple on left side) nearly all disappeared. A renewed attack of pelvic trouble while in the Hospital induced me to operate. The
Stronger Formaldehyde Regulation Sought
Authors: Bridget M. Kuehn
Journal: JAMA (2008)

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
Clinical trials of Ebola treatment to start in Africa
Authors: A. Gulland
Journal: BMJ (2014)

A £3.2m (€4.1m; $5.2m) grant to fund clinical trials of drugs to treat Ebola virus disease in west Africa will not be a “magic bullet” in containing the outbreak, and good public health measures were still needed, experts have said.

The UK charity the Wellcome Trust has announced that it will fund a consortium that will begin trials of treatments in the affected countries of Sierra Leone, Liberia, and Guinea in November. The consortium includes researchers from Oxford University, the charity Medecins Sans Frontieres, the World Health Organization, the Institut Pasteur, and the Institut Pasteur de Dakar.

Jeremy Farrar, director of the Wellcome Trust, told a press conference on 23 September that the two most promising treatments were plasma from convalescent patients and monoclonal antibodies such as the drug ZMapp. However, he said that if the trials were shown to be successful they would have …
Hypersensitivity Pneumonitis Induced by Toluene Diisocyanate: Sequelae of Continuous Exposure
Authors: Yasuyuki Yoshizawa
Journal: Annals of Internal Medicine (1989)

A 41-year-old automobile paint sprayer showed the clinical features of hypersensitivity pneumonitis 1 week after he had begun to work with paint materials containing toluene diisocyanate. His symptoms began 6 to 8 hours after exposure to the agent and spontaneously disappeared by the next morning. He had diffuse, fine reticulonodular shadows on a chest roentgenogram and a restrictive impairment of pulmonary function. Immunoglobulin G antibody to toluene diisocyanate-human serum albumin was present in bronchoalveolar lavage fluid and sera; IgA antibody was present only in bronchoalveolar lavage fluid. Also, the patient had sensitized bronchoalveolar lymphocytes to toluene diisocyanateserum albumin. The histologic findings suggested hypersensitivity pneumonitis. The results of bronchoalveolar lavage, which was repeated on four separate occasions, showed lymphocytosis and a predominance of suppressorcytotoxic T cells. The findings from serial determinations of humoral antibodies showed no changes consistent with the results of clinical and laboratory studies. In contrast, blastogenic responses of bronchoalveolar lymphocytes to toluene diisocyanate markedly decreased, and the patient showed clinical improvement despite continued exposure to the agent.
Cardiac Pacing in the 1980s
Authors: Paul L. Ludmer, Nora Goldschlager
Journal: New England Journal of Medicine (1984)

MORE than 500,000 patients in the United States live with the aid of a permanent cardiac pacing system to ensure a dependable cardiac rhythm, and this year another 100,000 will undergo pacemaker implantation.1 Now in its third decade, the field of cardiac pacing has undergone tremendous technological growth and development.2 , 3 Newer microchip-circuitry designs, as well as stable and reliable atrial and ventricular leads and electrodes, have led to complex multiprogrammable single- and dual-chamber generators with preservation of the normal atrioventricular sequence of cardiac activation (synchrony). However, the large number of available pacing systems has complicated the understanding of newer generator . . .
Case 7-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case A seventy-year-old widow was admitted to the hospital because of mental confusion and weakness. Three months previously she entered another hospital for two weeks because of pain in the right upper quadrant of the abdomen, with radiation through to the back. At that time the hemoglobin was 65 per cent; the nonprotein nitrogen was 43 mg. and the fasting blood sugar 114 mg. per 100 ml. A cholecystogram was said to show a poorly functioning gall bladder, and an upper gastrointestinal series and a barium-enema examination demonstrated an atonic colon. An electrocardiogram showed a sinus tachycardia, with . . .
From the Food and Drug Administration. Update on zidovudine
Authors: S. L. Nightingale
Journal: JAMA (1988)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Successful Control of Burn-Wound Sepsis
Authors: Basil A. Pruitt
Journal: JAMA (1968)

Over the past three years, the use of a topical antibacterial burn cream has resulted in the successful control of burn-wound sepsis. This pathological state, which is characterized by the proliferation and penetration of 100,000 (10<sup>5</sup>) or more microorganisms per gram of tissue, with extensive, active lymphatic invasion and may or may not be associated with generalized sepsis and widespread organ involvement, was the cause of death in 60% of patients dying at this unit prior to 1964. Histologically, this progression is characterized by bacterial invasion through the dermis into the subcutaneous tissue and may produce a typical<i>Pseudomonas</i>vasculitis with perivascular bacterial proliferation and invasion with thrombosis. The clinical manifestations of this disease are those of degeneration of the granulation tissue in areas of third-degree burn with violaceous, sharply demarcated wound edges, embolic ecthyma in unburned skin and tissues, ileus with abdominal distention, hypothermia, and leukopenia. Such bacterial
Self-regulation of inflammatory cell trafficking in mice by the leukocyte surface apyrase CD39
Authors: Matthew C. Hyman, Danica Petrovic-Djergovic, Scott H. Visovatti, Hui Liao, Sunitha Yanamadala, Diane Bouïs, Enming J. Su, Daniel A. Lawrence, M. Johan Broekman, Aaron J. Marcus, David J. Pinsky
Journal: Journal of Clinical Investigation (2009)

Leukocyte and platelet accumulation at sites of cerebral ischemia exacerbate cerebral damage. The ectoenzyme CD39 on the plasmalemma of endothelial cells metabolizes ADP to suppress platelet accumulation in the ischemic brain. However, the role of leukocyte surface CD39 in regulating monocyte and neutrophil trafficking in this setting is not known. Here we have demonstrated in mice what we believe to be a novel mechanism by which CD39 on monocytes and neutrophils regulates their own sequestration into ischemic cerebral tissue, by catabolizing nucleotides released by injured cells, thereby inhibiting their chemotaxis, adhesion, and transmigration. Bone marrow reconstitution and provision of an apyrase, an enzyme that hydrolyzes nucleoside tri- and diphosphates, each normalized ischemic leukosequestration and cerebral infarction in CD39-deficient mice. Leukocytes purified from Cd39-/- mice had a markedly diminished capacity to phosphohydrolyze adenine nucleotides and regulate platelet reactivity, suggesting that leukocyte ectoapyrases modulate the ambient vascular nucleotide milieu. Dissipation of ATP by CD39 reduced P2X7 receptor stimulation and thereby suppressed baseline leukocyte alphaMbeta2-integrin expression. As alphaMbeta2-integrin blockade reversed the postischemic, inflammatory phenotype of Cd39-/- mice, these data suggest that phosphohydrolytic activity on the leukocyte surface suppresses cell-cell interactions that would otherwise promote thrombosis or inflammation. These studies indicate that CD39 on both endothelial cells and leukocytes reduces inflammatory cell trafficking and platelet reactivity, with a consequent reduction in tissue injury following cerebral ischemic challenge.
Medical Care in the Nursing Home
Authors: Joseph G. Ouslander
Journal: JAMA (1989)

EVERY day more than 1.5 million Americans awaken in 1 of close to 20 000 nursing homes.<sup>1</sup>Some of these facilities provide excellent care, but the poor quality of care provided by many nursing homes has been repeatedly documented in the lay press, medical literature, and congressional testimony (<i>Los Angeles Times</i>. February 17, 1989; pt 1:3).<sup>2-4</sup>While the problems of many nursing home residents are more functional and psychosocial than medical,<sup>1,5</sup>the increasing acuity of medical conditions in this population since the implementation of the prospective payment system<sup>6,7</sup>demands that physicians be intimately involved in care provided in nursing homes. Yet, the majority of primary care physicians do not participate in the care of nursing home residents,<sup>8</sup>and very few of those who do provide care for substantial numbers of nursing home residents have received formal training in geriatric medicine or long-term care. Physician visits
Antigenicity of the pollen proteins of various cultivars of <i>Olea europaea</i>
Authors: Y. Waisel, C. Geller‐Bernstein, N. Keynan, G. Arad
Journal: Allergy (1996)

The incidence of positive skin test responses among alopic subjects with suspected respiratory allergy was investigated with commercial and autochthonous pollen extracts of various cultivars of Olea europaea . Pollen was collected from olive trees of well‐defined cultivars, extracted, and separated by SDS‐PAGE. Immunoblots were used to identify the various IgE‐binding proteins of the pollen extracts of the various cultivars. The results revealed six predominant IgE‐binding bands, some of which appear in all the cultivars examined. The 18–20‐Da band (Ole e 1) appeared in only eight of the cultivars, but not in the nine others. The presence of specific IgE‐binding bands in the various pollen extracts and their correlation with the incidence of positive skin tests are discussed.
Power and Illness: The Failure and Future of American Health Policy
Authors: R Klein
Journal: BMJ (1994)

Daniel M Fox University of California Press, $20, pp 191 ISBN 0-520-08409-8

The theme of Daniel M Fox's study of American health care policy is simple but radical in its implications, and not just for the United States. It is that health care institutions are shaped by history - specifically by the inherited stock of ideas about the nature of the medical task - and that, in turn, these institutions then create interest groups which impede adaptation to new challenges. To put it more concretely, Professor Fox's argument is that the main health problem in the US, as elsewhere, is the management of chronic conditions …