tbuckley/cabot-search huggingface dataset:
Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial
Authors: Rhonda R Voskuhl, HeJing Wang, T C Jackson Wu, Nancy L Sicotte, Kunio Nakamura, Florian Kurth, Noriko Itoh, Jenny Bardens, Jacqueline T Bernard, John R Corboy, Anne H Cross, Suhayl Dhib-Jalbut, Corey C Ford, Elliot M Frohman, Barbara Giesser, Dina Jacobs, Lloyd H Kasper, Sharon Lynch, Gareth Parry, Michael K Racke, Anthony T Reder, John Rose, Dean M Wingerchuk, Allan J MacKenzie-Graham, Douglas L Arnold, Chi Hong Tseng, Robert Elashoff
Journal: The Lancet Neurology (2015)
Right ventricular suction: an important determinant of cardiac performance
Authors: A. La Gerche, P. Claus
Journal: Cardiovascular Research (2015)

This editorial refers to ‘The role of elastic restoring forces in right-ventricular filling’ by C.P. Del Villar et al. , pp. 45–55. 

It has long been stated that researchers can be divided into lumpers and splitters. With respect to cardiac physiology, there is a simple appeal in lumping all of the inter-related factors together and assessing global measures of cardiac performance. On the other hand, splitting the cardiac cycle into its individual mechanical properties provides an opportunity to identify specific determinants of global function. Del Villar et al. focus on the right ventricle (RV) and split this chamber's filling properties into active and passive components and, in doing so, identify RV restoring forces as being critical to overall cardiac performance.1 RV restoring forces act during the very earliest phases of diastole, but are determined by afterload and contractile function of both the RV and the left ventricle (LV). It would seem that the splitters have identified a key index of function, which would please the lumpers in their search for a measure which impacts globally.

The concept of early diastolic suction has been the source of debate and a clear definition of this phenomenon has proved elusive.2,3 Defining suction as performing work to draw blood into the ventricle is only consistent with a negative transmural pressure, relative to intra-pericardial pressure.4 However, Del Villar et al. 1 have taken a different approach and calibrated against atmospheric pressures, fixed …
Prophylactic Antibiotics in Surgery
Authors: K A Ludwig, M A Carlson, R E Condon
Journal: Annual Review of Medicine (1993)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study.
Authors: G Bertelli, A Gozza, G B Forno, M G Vidili, S Silvestro, M Venturini, L Del Mastro, O Garrone, R Rosso, D Dini
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the activity and tolerability of dimethylsulfoxide (DMSO) in the prevention of soft tissue toxicity after extravasation of cytotoxic drugs. PATIENTS AND METHODS From June 1991 to December 1994, all patients who had an extravasation during intravenous (IV) infusion of cytotoxic drugs in our institution were considered for an open, prospective study of preventive treatment with 99% DMSO, applied topically on the extravasation site every 8 hours for 7 days. Intermittent local cooling (for 1 hour three times daily) on the first 3 days was also used. RESULTS One hundred forty-four patients with extravasations of doxorubicin (n = 11), epirubicin (n = 46), mitomycin (n = 5), mitoxantrone (n = 13), cisplatin (n = 44), carboplatin (n = 6), ifosfamide (n = 14), and fluorouracil (n = 5) entered the study; 127 were assessable. Only one patient suffered an ulceration. The treatment was well tolerated, with mild local burning and a characteristic breath odor being the only side effects of DMSO application, even in cases in which treatment continued for up to 6 weeks to obtain remission of the symptoms of extravasation. CONCLUSION Topical DMSO is an effective and safe antidote that may be used with local cooling after extravasations of vesicant drugs other than those drugs for which standard interventions are defined.
GPs are inadequately equipped to manage growing demand for cancer care, study warns
Authors: Susan Mayor
Journal: BMJ (2015)

GPs are inadequately trained and resourced to manage the growing demand for cancer care in high income countries, an expert review has warned.

The report, published in the Lancet Oncology , highlighted the gap between the expectation from governments and health funders that healthcare will increasingly be managed in primary care and the predicted doubling of the need for cancer care over the next 15 years.1 A primary care doctor with 2000 patients currently has around 70 patients with or surviving cancer, but this will double to around 140 patients by 2040.

Representatives from primary care …
Structural Barriers to Diagnosis and Treatment of Cancer in Low- and Middle-Income Countries: The Urgent Need for Scaling Up
Authors: Eduardo Cazap, Ian Magrath, T. Peter Kingham, Ahmed Elzawawy
Journal: Journal of Clinical Oncology (2015)

Noncommunicable diseases are now recognized by the United Nations and WHO as a major public health crisis. Cancer is a main part of this problem, and health care systems are facing a great challenge to improve cancer care, control costs, and increase systems efficiency. The disparity in access to care and outcomes between high-income countries and low- and middle-income countries is staggering. The reasons for this disparity include cost, access to care, manpower and training deficits, and a lack of awareness in the lay and medical communities. Diagnosis and treatment play an important role in this complex environment. In different regions and countries of the world, a variety of health care systems are in place, but most of them are fragmented or poorly coordinated. The need to scale up cancer care in the low- and middle-income countries is urgent, and this article reviews many of the structural mechanisms of the problem, describes the current situation, and proposes ways for improvement. The organization of cancer services is also included in the analysis.
Glyburide vs Insulin and Adverse Pregnancy Outcomes
Authors: Shadi Rezai, Monica Vielman, Cassandra E. Henderson
Journal: JAMA Pediatrics (2015)

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 Pediatrics 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 Pediatrics journal
In Vivo and In Silico Investigation Into Mechanisms of Frequency Dependence of Repolarization Alternans in Human Ventricular Cardiomyocytes
Authors: Xin Zhou, Alfonso Bueno-Orovio, Michele Orini, Ben Hanson, Martin Hayward, Peter Taggart, Pier D. Lambiase, Kevin Burrage, Blanca Rodriguez
Journal: Circulation Research (2015)

Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determined by cell-to-cell variability in protein expression, which is regulated by genetic and external factors.To characterize in vivo RA in human and to investigate in silico using human models, the ionic mechanisms underlying the frequency-dependent differences in RA behavior identified in vivo.In vivo electrograms were acquired at 240 sites covering the epicardium of 41 patients at 6 cycle lengths (600-350 ms). In silico investigations were conducted using a population of biophysically detailed human models incorporating variability in protein expression and calibrated using in vivo recordings. Both in silico and in vivo, 2 types of RA were identified, with Fork- and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacing rates. In silico simulations show that RA are strongly correlated with fluctuations in sarcoplasmic reticulum calcium, because of strong release and weak reuptake. Large L-type calcium current conductance is responsible for RA disappearance at fast frequencies in Eye-type (30% larger in Eye-type versus Fork-type; P<0.01), because of sarcoplasmic reticulum Ca(2+) ATPase pump potentiation caused by frequency-induced increase in intracellular calcium. Large Na(+)/Ca(2+) exchanger current is the main driver in translating Ca(2+) fluctuations into RA.In human in vivo and in silico, 2 types of RA are identified, with RA persistence/disappearance as frequency increases. In silico, L-type calcium current and Na(+)/Ca(2+) exchanger current determine RA human cell-to-cell differences through intracellular and sarcoplasmic reticulum calcium regulation.
Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.
Authors: S Wadler, B Lembersky, M Atkins, J Kirkwood, N Petrelli
Journal: Journal of Clinical Oncology (1991)

In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable.
Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF)
Authors: Henning Grønbæk, Sidsel Rødgaard-Hansen, Niels Kristian Aagaard, Vicente Arroyo, Søren K. Moestrup, Elisabet Garcia, Elsa Solà, Marco Domenicali, Salvatore Piano, Hendrik Vilstrup, Holger Jon Møller
Journal: Journal of Hepatology (2015)
Comment on Erondu et al. Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program. Diabetes Care 2015;38:1680–1686
Authors: Horng-Yih Ou, Rudruidee Karnchanasorn, Lee-Ming Chuang, Ken C. Chiu
Journal: Diabetes Care (2015)

In the recent analysis of the canagliflozin trials, Erondu et al. (1) reported the incidence of acidosis, including diabetic ketoacidosis (DKA), in patients with type 2 diabetes (T2D) receiving canagliflozin treatment. Although it is highly persuasive that sodium–glucose cotransporter 2 inhibitors could increase the risk of DKA from a mechanistic standpoint (2), there are three issues that desire some comments.

In contrast to the report from the U.S. Food and Drug Administration (3) and the recent case reports by Peters et al. (4), blood glucose levels were markedly elevated in almost all 12 patients except …
Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis
Authors: Poh-Yi Gan, Kim M. O’Sullivan, Joshua D. Ooi, Maliha A. Alikhan, Dragana Odobasic, Shaun A. Summers, A. Richard Kitching, Stephen R. Holdsworth
Journal: Journal of the American Society of Nephrology (2015)

Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4 + effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV.
WR-2721 protects against the hematologic toxicity of cyclophosphamide: a controlled phase II trial.
Authors: D Glover, J H Glick, C Weiler, S Hurowitz, M M Kligerman
Journal: Journal of Clinical Oncology (1986)

WR-2721 S-2-(3-aminopropylamino) ethyl phosphorothioic acid, is an organic thiophosphate compound that in the animal model selectively protects against the hematologic toxicity of cyclophosphamide by factors of 1.5 to 2.0. Preliminary data from our controlled phase I trial of WR-2721 and cyclophosphamide suggested that WR-2721 protected against cyclophosphamide-induced granulocytopenia. Since variable drug doses and infusion rates were used in these early studies, we initiated a controlled phase II trial using constant drug doses to establish more precisely WR-2721's level of protection. Initially, 21 patients received 1,500 mg/m2 of cyclophosphamide alone and were retreated 4 weeks later after hematologic recovery was complete with 740 mg/m2 of WR-2721 before the same dose of cyclophosphamide. With WR-2721 pretreatment, 19 of 21 (90%) patients had improved WBC and granulocyte counts. The mean WBC increased from 1,760/mL with cyclophosphamide alone to 2,500/mL with WR-2721 pretreatment (P less than .0005). The mean granulocyte count increased from 541/mL on cyclophosphamide to 1,247/mL with WR-2721 and cyclophosphamide (P less than .0005). Following cyclophosphamide administration alone, neutropenic fevers developed in three patients. No patient experienced a febrile episode following WR-2721 and cyclophosphamide administration. Platelet nadirs below 100,000/mL were only noted in two patients treated with cyclophosphamide alone. Objective partial responses were observed in four of 19 (21%) patients with measurable or evaluable disease. These data suggest that WR-2721 provides significant protection against cyclophosphamide-induced hematologic toxicity.
Number, activation, and differentiation of circulating fibrocytes correlate with asthma severity
Authors: Ryan Shipe, Marie D. Burdick, Brett A. Strieter, Ling Liu, Yun Michael Shim, Sun-sang Sung, W. Gerald Teague, Borna Mehrad, Robert M. Strieter, C. Edward Rose
Journal: Journal of Allergy and Clinical Immunology (2015)
The old knee in the young athlete: knowns and unknowns in the return to play conversation
Authors: Clare L Ardern, Karim M Khan
Journal: British Journal of Sports Medicine (2015)

Twenty-year-old Sarah is a sport-obsessed amateur football player. She enjoys the social side of playing in a team sport, but most of all she loves the physical and mental challenge of game day. There is no better feeling than winning. She works hard on her skills and fitness, training twice a week with the team, and most other days on the cycle commute to the University and with her own gym programme. Maybe it was her young age1 and dodgy biomechanics2 that conspired against her. Perhaps it was the type of grass on her home pitch.3 But she winds up at your clinic clutching an MRI report that bears the dreaded diagnosis—she's ruptured her ACL.

Return to play is a fundamental concern for athletes and sports medicine clinicians—one important benchmark for judging treatment success. For many athletes with ACL injury, their most pressing concerns are about meeting their own expectations, or those of significant others (eg, coach, team mates, family), for returning to their pre-injury level or sports performance. Sarah will be faced with three options when she is ready to return to play—return to the pre-injury level sport, change sports participation (either change sport or change level) or retire.

Fact 1 : Excellent physical function on impairment-based and activity-based …
Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid: A proof‐of‐concept study
Authors: Gideon M. Hirschfield, M. Eric Gershwin, Richard Strauss, Marlyn J. Mayo, Cynthia Levy, Bin Zou, Jewel Johanns, Ivo P. Nnane, Bidisha Dasgupta, Katherine Li, Carlo Selmi, Hanns‐Ulrich Marschall, David Jones, Keith Lindor
Journal: Hepatology (2015)

The interleukin (IL)‐12 signaling cascade has been associated with primary biliary cholangitis (PBC). This multicenter, open‐label, proof‐of‐concept study evaluated the anti‐IL12/23 monoclonal antibody, ustekinumab (90 mg subcutaneous at weeks 0 and 4, then every 8 weeks through week 20), in adults with PBC and an inadequate response to ursodeoxycholic acid therapy (i.e., alkaline phosphatase [ALP] &gt;1.67× upper limit of normal [ULN] after ≥6 months). ALP response was defined as a &gt;40% decrease from baseline and ALP remission as ALP normalization (if baseline ALP 1.67×‐2.8× ULN) or &lt;1.67× ULN (if baseline ALP &gt;2.8× ULN). Changes in Enhanced Liver Fibrosis (ELF) scores and serum bile acids were also assessed. At baseline, patients had median disease duration of 3.2 years, median ELF score of 9.8, and highly elevated total bile acid concentration (median, 43.3 μmol/L); 13 of 20 (65%) patients had baseline ALP &gt;3× ULN. Although steady‐state serum ustekinumab concentrations were reached by week 12, no patient achieved ALP response or remission. Median percent ALP reduction from baseline to week 28 was 12.1%. ELF score decreased slightly from baseline to week 28 (median reduction: 0.173), and total serum bile acid concentrations decreased from baseline to week 28 (median reduction: 8.8 μmol/L). No serious infections or discontinuations resulting from adverse events were reported through week 28. One patient had a serious upper gastrointestinal hemorrhage considered unrelated to test agent by the investigator. Conclusion: Open‐label ustekinumab therapy, though associated with a modest decrease in ALP after 28 weeks of therapy, did not otherwise appreciably change ALP and overt proof‐of‐concept was not established as per prespecified primary endpoint of proposed efficacy. No new ustekinumab safety signals were observed. (H epatology 2016;64:189‐199)
Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men
Authors: Guenther Boden, Carol Homko, Carlos A. Barrero, T. Peter Stein, Xinhua Chen, Peter Cheung, Chiara Fecchio, Sarah Koller, Salim Merali
Journal: Science Translational Medicine (2015)

Acute overnutrition in healthy men caused rapid weight gain and insulin resistance, as well as oxidative stress.
Effect of employment and social medical insurance on hospital admissions for people living with multimorbidity in China: analysis of a large community household survey
Authors: Harry H X Wang, Jia Ji Wang, Samuel Y S Wong, Martin C S Wong, Fang Jian Li, Pei Xi Wang, Zhi Heng Zhou, Chun Yan Zhu, Sian M Griffiths, Stewart W Mercer
Journal: The Lancet (2015)
Medial Prefrontal Aberrations in Major Depressive Disorder Revealed by Cytoarchitectonically Informed Voxel-Based Morphometry
Authors: Sebastian Bludau, Danilo Bzdok, Oliver Gruber, Nils Kohn, Valentin Riedl, Christian Sorg, Nicola Palomero-Gallagher, Mueller Veronika, Felix Hoffstaedter, Katrin Amunts, B Simon, M. D. Eickhoff
Journal: American Journal of Psychiatry (2015)

Objective: The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The authors performed morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and comparison subjects using both uni- and multivariate statistics. Method: Multisite voxel- and region-based morphometric MRI analysis was conducted in 73 depressed patients and 73 matched comparison subjects without psychiatric history. Frontal pole volume was first compared between depressed patients and comparison subjects by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. Results: Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients, with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients. Conclusions: Across disparate methods, subregion specificity in the left medial frontal pole volume in depressed patients was demonstrated. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology, such as the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression.