tbuckley/cabot-search huggingface dataset:
A Comparison of Magnesium Sulfate and Nimodipine for the Prevention of Eclampsia
Authors: Michael A. Belfort, John Anthony, George R. Saade, John C. Allen
Journal: New England Journal of Medicine (2003)

Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia.We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure.Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001).Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.
Ileal V˙<scp>o</scp> <sub>2</sub>–D˙<scp>o</scp> <sub>2</sub> Alterations Induced by Endotoxin Correlate with Severity of Mitochondrial Injury
Authors: ELLIOTT D. CROUSER, MARK W. JULIAN, PAUL M. DORINSKY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Sepsis is usually associated with altered O2 metabolism in systemic organs. Until recently, inadequate O2 delivery was thought to be the putative mechanism underlying these metabolic alterations. However, current investigations suggest that impaired O2 consumption due to disrupted O2 use by mitochondria may be the culprit. Therefore, we hypothesized that endotoxin (LPS)-induced V˙ o 2–D˙ o 2 alterations would correlate with the severity of mitochondrial injury in a systemic organ (i.e., the ileum). Using an in situ autoperfused feline ileum preparation, we assessed V˙ o 2–D˙ o 2 relationships and mitochondrial ultrastructure after 2 h in LPS-treated (3 mg/kg, intravenous; n = 11) and time-matched control (n = 5) animals. Mitochondrial injury was graded in a blinded fashion on the basis of characteristics associated with established stages of cell injury. LPS-treated animals developed severe mitochondrial injury in the ileal mucosa despite unchanged regional tissue perfusion and ileal oxyhemoglobin levels compared with controls. Worsening of mitochondrial injury correlated with increases in the critical O2 delivery (r = 0.85; p < 0.002) and decreases in the maximum O2 extraction (r = − 0.61; p < 0.02) in the ileum. These results suggest that mitochondrial injury, leading to impaired O2 utilization, may be primarily responsible for altered V˙ o 2–D˙ o 2 relationships in systemic organs during sepsis.
Real-Time Immune Monitoring to Guide Plasmid DNA Vaccination Schedule Targeting Prostatic Acid Phosphatase in Patients with Castration-Resistant Prostate Cancer
Authors: Douglas G. McNeel, Jordan T. Becker, Jens C. Eickhoff, Laura E. Johnson, Eric Bradley, Isabel Pohlkamp, Mary Jane Staab, Glenn Liu, George Wilding, Brian M. Olson
Journal: Clinical Cancer Research (2014)

We have previously reported that a DNA vaccine encoding prostatic acid phosphatase (PAP) could elicit PAP-specific T cells in patients with early recurrent prostate cancer. In the current pilot trial, we sought to evaluate whether prolonged immunization with regular booster immunizations, or "personalized" schedules of immunization determined using real-time immune monitoring, could elicit persistent, antigen-specific T cells, and whether treatment was associated with changes in PSA doubling time (PSA DT).Sixteen patients with castration-resistant, nonmetastatic prostate cancer received six immunizations at 2-week intervals and then either quarterly (arm 1) or as determined by multiparameter immune monitoring (arm 2).Patients were on study a median of 16 months; four received 24 vaccinations. Only one event associated with treatment >grade 2 was observed. Six of 16 (38%) remained metastasis-free at 2 years. PAP-specific T cells were elicited in 12 of 16 (75%), predominantly of a Th1 phenotype, which persisted in frequency and phenotype for at least 1 year. IFNγ-secreting T-cell responses measured by ELISPOT were detectable in 5 of 13 individuals at 1 year, and this was not statistically different between study arms. The overall median fold change in PSA DT from pretreatment to posttreatment was 1.6 (range, 0.6-7.0; P = 0.036).Repetitive immunization with a plasmid DNA vaccine was safe and elicited Th1-biased antigen-specific T cells that persisted over time. Modifications in the immunization schedule based on real-time immune monitoring did not increase the frequency of patients developing effector and memory T-cell responses with this DNA vaccine.
Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues.
Authors: L B Jakeman, J Winer, G L Bennett, C A Altar, N Ferrara
Journal: Journal of Clinical Investigation (1992)

Vascular endothelial growth factor (VEGF) is a secreted heparin-binding mitogen; its growth-promoting activity is limited to vascular endothelial cells in vitro and VEGF also stimulates angiogenesis in vivo. To identify target cells for VEGF and investigate the potential physiological role of this factor, iodinated recombinant human VEGF (125I-rhVEGF) was used for in vitro ligand autoradiography on tissue sections from adult rats. 125I-rhVEGF exhibited saturable, displaceable binding to a single class of sites with high affinity and low capacity in all tissues and organs examined. Colocalization of 125I-rhVEGF binding with Factor VIII-like immunoreactivity demonstrated binding sites associated with vascular endothelial cells of both fenestrated and nonfenestrated microvessels and the endothelium of large vessels, while no displaceable binding was evident on nonendothelial cells. Specific binding was associated with quiescent as well as proliferating vessels. These findings support the hypothesis that VEGF plays a specific role in both the maintenance and in the induction of growth of vascular endothelial cells.
Arrhythmogenic Right Ventricular Dysplasia
Authors: Darshan Dalal, Khurram Nasir, Chandra Bomma, Kalpana Prakasa, Harikrishna Tandri, Jonathan Piccini, Ariel Roguin, Crystal Tichnell, Cynthia James, Stuart D. Russell, Daniel P. Judge, Theodore Abraham, Philip J. Spevak, David A. Bluemke, Hugh Calkins
Journal: Circulation (2005)

Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by right ventricular dysfunction and ventricular arrhythmias. The purpose of our study was to describe the presentation, clinical features, survival, and natural history of ARVD in a large cohort of patients from the United States.The patient population included 100 ARVD patients (51 male; median age at presentation, 26 [interquartile range {IQR}, 18 to 38; range, 2 to 70] years). A familial pattern was observed in 32 patients. The most common presenting symptoms were palpitations, syncope, and sudden cardiac death (SCD) in 27%, 26%, and 23% of patients, respectively. Among those who were diagnosed while living (n=69), the median time between first presentation and diagnosis was 1 (range, 0 to 37) year. During a median follow-up of 6 (IQR, 2 to 13; range, 0 to 37) years, implantable cardioverter/defibrillators (ICD) were implanted in 47 patients, 29 of whom received an appropriate ICD discharge, including 3 patients who received the ICD for primary prevention. At follow-up, 66 patients were alive, of whom 44 had an ICD in place, 5 developed signs of heart failure, 2 had a heart transplant, and 18 were on drug therapy. Thirty-four patients died either at presentation (n=23: 21 SCD, 2 noncardiac deaths) or during follow-up (n=11: 10 SCD, 1 of biventricular heart failure), of whom only 3 were diagnosed while living and 1 had an ICD implanted. On Kaplan-Meier analysis, the median survival in the entire population was 60 years.ARVD patients present between the second and fifth decades of life either with symptoms of palpitations and syncope associated with ventricular tachycardia or with SCD. Diagnosis is often delayed. Once diagnosed and treated with an ICD, mortality is low. There is a wide variation in presentation and course of ARVD patients, which can likely be explained by the genetic heterogeneity of the disease.
Effect of Fresh Plasma Infusions on the Sensitized Sheep Cell Agglutination Reaction in Cases of Rheumatoid Disease
Authors: J. D. Gray
Journal: Annals of the Rheumatic Diseases (1962)

Scotiaabsent, serum uric acid 4-3 mg. per cent., Rose-Waaler Control -0 test 1: 64.Case 3, a 41-year-old woman, had stiffness on getting out of bed which eased somewhat after moving around, and swelling of the hands and wrists; 4 years previously she had been given Butazolidin and this had caused an acute agranulocytosis.She now complained of being chronically tired and her appetite was poor.Small rheumatoid nodules could be felt over each olecranon bursa.The spleen was palpable.The elbows lacked 194
Resistance to Flow of Arterial Y-Grafts 6 Months After Coronary Artery Bypass Surgery
Authors: David Glineur, Philippe Noirhomme, Jim Reisch, Gebrine El Khoury, Parla Astarci, Claude Hanet
Journal: Circulation (2005)

The use of both internal thoracic arteries (ITAs) as a Y-graft configuration has been proposed as a technique allowing complete arterial revascularization. Controversy remains, however, about the capacity of this Y-graft configuration to provide sufficient blood flow to the whole left coronary system and about possible steal phenomenon occurring during periods of maximal myocardial blood flow demand.To evaluate graft conductance 6 months after Y-graft revascularization of the left coronary system with both ITAs, 11 consecutive patients were studied during cardiac catheterization. In all of the cases, the left ITA had been connected to the left anterior descending coronary artery (LAD) territory (mean, 1.3 anastomoses), and the free right ITA was anastomosed proximally to the left ITA and distally to the left circumflex (LCX) territory (mean, 1.9 anastomoses). Pressure and fractional flow reserve (FFR) were recorded using a 0.014-inch pressure wire advanced distally in the left ITA main stem close to the proximal anastomosis of the free right ITA (ITA-stem) and in the distal part of each ITA branch at the site of their implantation to the LAD (ITA-LAD) or LCX (ITA-LCX) system. At each of these sites, the pressure gradient between aorta and the graft was measured in basal condition and during maximal hyperemia induced by intragraft bolus injection of 40 microg of adenosine. In basal conditions, the pressure gradient was minimal between the aorta and the ITA-stem (2+/-2 mm Hg), the ITA-LAD (3+/-3 mm Hg), and the ITA-LCX (3+/-2 mm Hg; P value was not significant versus ITA-LAD). During maximal hyperemia, the pressure gradient increased to 7+/-2 mm Hg in the ITA-stem, to 9+/-5 mm Hg in the ITA-LAD, and to 9+/-3 in the ITA-LCX (P value not significant versus ITA-LAD). The fractional flow reserve was 0.93+/-0.03 in the ITA-stem, 0.91+/-0.04 in the ITA-LAD, and 0.91+/-0.03 in the ITA-LCX.A Y-graft configuration with a free right ITA attached to a pedicled left ITA allows an adequate revascularization of the whole left coronary system with an even distribution of perfusion pressure in both distal branches and minimal resistance to maximal blood flow.
Familial Risk of Lung Carcinoma in the Icelandic Population
Authors: Steinn Jonsson
Journal: JAMA (2004)

The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma.To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population.Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR.Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers.A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset < or =60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking.These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.
Cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events in the Basel Stent KostenEffektivitäts Trial (BASKET): an 18-month analysis
Authors: Hans Peter Brunner-La Rocca, Christoph Kaiser, Alain Bernheim, Michael J Zellweger, Raban Jeger, Peter T Buser, Stefan Osswald, Matthias Pfisterer
Journal: The Lancet (2007)
Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong
Authors: S. Yan Man, N. Lee, M. Ip, G. E Antonio, S. S L Chau, P. Mak, C. A Graham, M. Zhang, G. Lui, P. K S Chan, A. T Ahuja, D. S Hui, J. J Y Sung, T. H Rainer
Journal: Thorax (2006)

Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong.To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65.A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared.The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%).All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.
Measurement of Mitral Regurgitation by IndicatorDilution Tecirniques
Authors: WILLIAM H. LEVISON, WILLIAM D. JACKSON, HERBERT SHERMAN, LOCKHART B. MCGUIIRE
Journal: Circulation Research (1961)

ethocls f o r q u a n t i f y i n g initral regurgitation that require the measurenlent only of tlie area enclosecl by the inclicator-clilution curves offer the advantage of being computationally simpler tha11 the others. Furthermore, clistortions in the shape of t h e curve will not necessarily induce significant error in the area enclosecl by the curve. Since such methocls require sampling from t h e a t r i u m as well as from the ventricle, or proximal aorta, the?- will lw successful only if meaningful samples uf indicator concentration can he obtained from these chambers. The cluestion remains to be arc$\\-erecl: 13 the mixing in the cardiac chambers sufficient to allow meaningful sampling in both atrium and rentricle? A review of the literature on this, subject 11s been inconclusive."-" MTe iwe not aware of any experiments in which all of the conclitions aftecting cardiac chamber mising have been controllecl without seriously disturbing normal carcliac physiology. Such ;in experiment shoulcl control the nature of injection (i.e., one or mauy successi\-e pulses). the number ancl placement of the orifices a t the tip of the injection catheter, ancl the timing of the i u j e c t i o ~ l with the carcliac cycle. Experiments indicate t h a t the optim~um mixing conclitions exist at the beginning of ventricular filling ancl that injection should be timed to coincide with this point in tlw cycle. I t is of interest to note that, in the clye curve e x p e r i m e ~ ~ t s by Sinclair et al.Ix in whic.11 animals were used, t h e time a t which injcctions were macle was found to be unimportant. 'I'his important difference between t11c mising characteristics of the mechanical ~noclcl and an animal lieart illustrates the cliificulties cncountered in the application of moclel results ancl observations to the human heart. It seems reasonable to conjecture, ho\vever, that the \\,ell-estal~lisl~ecl mixing properties of flows through valves ancl orifiws in ripicl systems will be enhancecl in the cleformable wall situation encountered in the h r a r t . F u r t h e r experiments using the indicator-dilution technique on both normal ancl abnormal hearts are evidently requirecl t o determine the nature ancl extent of tlie clepenclence of measurement reliability on the sanipling site location.
Longitudinal evaluation of MPIO-labeled stem cell biodistribution in glioblastoma using high resolution and contrast-enhanced MR imaging at 14.1Tesla
Authors: M. M. Chaumeil, B. Gini, H. Yang, A. Iwanami, S. Sukumar, T. Ozawa, R. O. Pieper, P. S. Mischel, C. D. James, M. S. Berger, S. M. Ronen
Journal: Neuro-Oncology (2012)

To optimize the development of stem cell (SC)–based therapies for the treatment of glioblastoma (GBM), we compared the pathotropism of 2 SC sources, human mesenchymal stem cells (hMSCs) and fetal neural stem cells (fNSCs), toward 2 orthotopic GBM models, circumscribed U87vIII and highly infiltrative GBM26. High resolution and contrast-enhanced (CE) magnetic resonance imaging (MRI) were performed at 14.1Tesla to longitudinally monitor the in vivo location of hMSCs and fNSCs labeled with the same amount of micron-size particles of iron oxide (MPIO). To assess pathotropism, SCs were injected in the contralateral hemisphere of U87vIII tumor-bearing mice. Both MPIO-labeled SC types exhibited tropism to tumors, first localizing at the tumor edges, then in the tumor masses. MPIO-labeled hMSCs and fNSCs were also injected intratumorally in mice with U87vIII or GBM26 tumors to assess their biodistribution. Both SC types distributed throughout the tumor in both GBM models. Of interest, in the U87vIII model, areas of hyposignal colocalized first with the enhancing regions (ie, regions of high vascular permeability), consistent with SC tropism to vascular endothelial growth factor. In the GBM26 model, no rim of hyposignal was observed, consistent with the infiltrative nature of this tumor. Quantitative analysis of the index of dispersion confirmed that both MPIO-labeled SC types longitudinally distribute inside the tumor masses after intratumoral injection. Histological studies confirmed the MRI results. In summary, our results indicate that hMSCs and fNSCs exhibit similar properties regarding tumor tropism and intratumoral dissemination, highlighting the potential of these 2 SC sources as adequate candidates for SC-based therapies.
Curtailment of higher surgical training in the UK: likely effects in otology
Authors: J Ray
Journal: Journal of the Royal Society of Medicine (2005)

Higher surgical training in the UK faces a cut of two years. We conducted a questionnaire survey to assess the operative experience of current higher surgical trainees in otological surgery and the likely effect of the proposed reduction from six to four years. 91 (65%) of the 142 higher surgical trainees responded with details of major otological procedures performed (independently or assisting) over one year. In the present six-year scheme a typical trainee performs 72 myringoplasties, 79 mastoidectomies, 7 skull base procedures and 28 other procedures. In the first four years, however, his or her experience is only 39 myringoplasties, 44 mastoidectomies, 4 skull base procedures and 7 others. The large shortfall in experience that might result from shortening of the training programme would need to be met by intensification of the training or institution of accredited otology fellowships. Very similar dilemmas are faced by other surgical specialties.