tbuckley/cabot-search huggingface dataset:
Long-Term Survival and Late Deaths After Allogeneic Hematopoietic Cell Transplantation
Authors: John R. Wingard, Navneet S. Majhail, Ruta Brazauskas, Zhiwei Wang, Kathleen A. Sobocinski, David Jacobsohn, Mohamed L. Sorror, Mary M. Horowitz, Brian Bolwell, J. Douglas Rizzo, Gérard Socié
Journal: Journal of Clinical Oncology (2011)

Purpose Allogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied. Patients and Methods Records of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed. Results Median follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time. Conclusion The prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.
Abstract 9611: Enhancing the “Paracrine Effects” of Mesenchymal Stem Cells to Recover Damaged Myocardium by the Use of Cell-Sheets
Authors: Takuya Narita, Yasunori Shintani, Chiho Ikebe, Narumi Harada, Masahiro Kaneko, Niall G Campbell, Vinit Sawhney, Steven R Coppen, Kenta Yashiro, Ken Suzuki
Journal: Circulation (2011)

Recent research has shown that transplantation of mesenchymal stem cells (MSCs) recovers failing hearts mainly via paracrine effects and has prompted clinical trials of intramyocardial injection of MSC suspensions. However, this method is associated with trypsinisation-induced MSC damage and injection-related injury/inflammation of host myocardium. It is now possible to generate “cell-sheets” by means of temperature-responsive culture dishes without using disruptive reagents. Epicardial placement of MSC-sheets will be able to deliver MSCs with higher viability and functionality whilst obviating damage to the host myocardium. This will enhance the paracrine effects, by improving both MSC secretion and host myocardium response, leading to amplified therapeutic effects. Methods &amp; Results: After coronary artery ligation in female rats, 4 million bone marrow derived MSCs from syngeneic male rats were grafted by either intramyocardial injection (IM) or cell-sheet placement (CS). Sham treated rats served as control (Cont). Donor MSC survival was markedly increased in CS compared to IM. The majority of MSCs in CS remained at the epicardial surface, avoiding myocardial accumulation of inflammatory cells. Shortly after sheet placement, the epicardium degenerated, allowing permeation of MSC-secreted mediators into the myocardium. Differentiation of donor MSCs to cardiac or mesenchymal lineages was not observed. IM showed upregulation of HIF1α, bFGF, IL10, VCAM1, MMP2, TIMP1, IGF1, SDF1, which was associated with favorable modulations in host cardiac tissues. Of note, these molecular and cellular changes were significantly amplified in CS, in correlation to further enhanced cardiac function. Conclusion: The cell-sheet technique improved donor MSC engraftment whilst preserving the host myocardium, resulting in augmentation of MSC-derived paracrine effects, compared to the current method. These data encourage clinical application of this approach.
Effects of Changes in Coronary Blood pH on the Heart
Authors: HSUEH-HWA WANG, RONALD L. KATZ
Journal: Circulation Research (1965)

The effects of localized acidosis and alkalosis on coronary blood flow, myocardial contractile force, and heart rate were studied in anesthetized, open-chest dogs. Acidosis of the coronary vascular bed was induced by infusion of 5,5-dimethyl-2, 4-oxazolidinedion (DMO) into the total coronary artery inflow, and alkalosis by infusion of tris hydroxymethyl aminomethane (THAM), Na 2 CO 3 or NaHCO 3 . DMO infusion caused an initial slight increase of coronary blood flow, followed by a decrease. The decrease was accompanied by and attributed to a moderate to marked decrease of myocardial contractile force and bradycardia. THAM and Na 2 CO 3 infusion caused a marked increase of coronary blood flow, associated with a decrease of coronary oxygen A-V difference, indicating coronary vasodilation. A slight to moderate increase of myocardial contractile force but little or no change in heart rate was noted. NaHCO 3 infusion caused changes similar to those induced by DMO but of smaller magnitude. It was suggested that the direct effects of DMO and NaHCO 3 are attributable to intracellular acidosis, whereas those of THAM and Na 2 CO 3 are attributable to intracellular alkalosis.
PHOTOSENSITIZATION OF ANIMALS AFTER THE INGESTION OF BUCKWHEAT
Authors: Charles Sheard, Harold D. Caylor, Carl Schlotthauer
Journal: The Journal of Experimental Medicine (1928)

THE CHIEF POINTS PRESENTED IN THIS PAPER ARE: 1. Following the ingestion of buckwheat (plant or seed) varicolored guinea pigs, white swine and goats exhibited symptoms of photosensitization, the degree of sensitization being in the order given. 2. Rabbits, dogs, white mice and rats did not manifest symptoms of photosensitization. 3. The symptoms and reactions were: agitation, itching, scratching of the ears, weakness, urticaria with sloughing and symptoms similar to those in anaphylaxis. 4. Microscopic examinations showed the lack of marked pathologic change. The lesions, such as petechial hemorrhage of the lungs, brain, liver, stomach and kidneys, suggest that profound toxemia has been present. 5. Lesions were not found which appeared to be suggestive of malignant neoplasms. 6. Irradiation by a quartz mercury vapor lamp apparently develops a resistance to photosensitization, probably because of increased pigmentation induced by ultra-violet light. 7. From the nature of the physiologic and pathologic reactions produced under various filters and from a consideration of the percentages of transmission of solar energy in the visible spectrum, it would seem that the region of photosensitization lies between 580 millimicrons (yellow) and the red end of the spectrum. This conclusion, moreover, is substantiated by the fact that irradiation by a quartz mercury vapor lamp (which radiates no energy in the visible spectrum at a wave-length greater than 579 millimicrons) produces no symptoms or reactions. 8. Spectrophotometric determinations of alcoholic extracts of grass (non-toxic) and of buckwheat (toxic) show the presence of two additional bands in the absorption spectrum of buckwheat with maxima at about 540 and 600 millimicrons, respectively, together with the common absorption zones at 430 to 490 millimicrons and 630 to 690 millimicrons. 9. Spectrophotometric determinations of blood serums of sensitized animals show, besides the usual absorption bands peculiar to oxyhemoglobin (with maxima at 540 and 580 millimicrons respectively), two zones with maxima at 600 and 660 millimicrons respectively. 10. The fluorescence of chlorophyll per se, as suggested by previous investigators, is not, in all probability, the cause of the sensitization induced by buckwheat. 11. Hematoporphyrine is not the photodynamic substance in all probability. 12. Phylloporphyrine may be the photodynamic substance. In this regard, also, the possibility of cholehematin is not to be ruled out.
Oscillatory Resistance Measured during Noninvasive Proportional Assist Ventilation
Authors: RAMON FARRÉ, MARCO MANCINI, MAR ROTGER, MIQUEL FERRER, JOSEP ROCA, DANIEL NAVAJAS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Setting proportional assist ventilation (PAV) requires the measurement of patient resistance and elastance. To avoid patient sedation/paralysis or the use of an esophageal balloon, noninvasive PAV is indirectly set by the "runaway" method or in accordance with patient comfort. The aim of this study was to ascertain whether the forced oscillation technique (FOT) applied by the ventilator during noninvasive PAV is useful in assessing patient respiratory resistance. Nasal PAV was applied to 14 patients with severe chronic obstructive pulmonary disease. During PAV a modified ventilator applied a 5-Hz pressure oscillation to noninvasively assess FOT resistance (Rrs). Lung resistance (Rl) was measured in seven of the patients by using an esophageal balloon. Moreover, measurements were also performed in five of the patients when PAV was applied through the mouth. Rrs was close to Rl both during nasal (Rrs = 8.9 ± 3.1, Rl = 9.0 ± 2.6; cm H2O · s/L; n = 7, p > 0.05) and mouth (Rrs = 5.6 ± 2.1, Rl = 5.8 ± 1.4; cm H2O · s/L; n = 5, p > 0.05) breathing. Rrs was slightly greater than the maximum value of flow assistance applied during the setting of PAV (FAmax): 11.1 ± 5.4 and 9.5 ± 2.9 cm H2O · s/L, respectively (n = 14, p > 0.05), both variables being significantly correlated (r = 0.72, p < 0.05). FOT applied by the PAV ventilator allowed the assessment of patient resistance. These results suggest that FOT could be useful in setting PAV flow assistance and in automatically and continuously updating this setting in accordance with patient resistance.
Physiological adjustments to intensive interval treadmill training
Authors: F. S. Pyke, B. C. Elliott, A. R. Morton, A. D. Roberts
Journal: British Journal of Sports Medicine (1974)

During a one month training period, eight active men, aged 23-35 years, completed sixteen 30 minute sessions of high intensity interval (5 second work bouts at 16.9 km/hr up 20-25% grade alternated with 10 second rest intervals) treadmill work. In this training period, V̇O 2 , V̇ E and blood lactate in a 10 minute run at 12.9 km/hr on a level treadmill were unchanged but heart rate during this work decreased by an average of 9 beats/min. During a 4 minute interval work effort at the training intensity, blood lactate accumulation decreased by 40.4%. In exhausting work, mean values of V̇O 2 , V̇ E and blood lactate increased by 6.2%, 8.2% and 31.6% respectively. Maximal heart rate decreased by an average of 4 beats/min. The average work production of the men in the training sessions improved by 64.5% from 28,160 kgm to 43,685 kgm. No significant improvements were observed in either a short sprint or a stair climbing test which assessed the ability to generate mechanical power from alactacid anaerobic sources. It was concluded that the training regime is an effective method of producing a high total work output in competitive athletes and results in improvements in aerobic power, glycolytic capacity and ability to tolerate the short duration interval work encountered in many games.
Prevalence and Sources of Patients' Unmet Expectations for Care
Authors: Richard L. Kravitz
Journal: Annals of Internal Medicine (1996)

Background: Patients' expectations and the role they play in medical care are increasingly considered to be important, but the factors that influence these expectations have not been well studied. Objective: To examine the factors that influence patients' expectations for care in office practice. Design: Qualitative inquiry nested within a large clinical survey. Setting: Three general internal medicine practices in one mid-sized city in northern California. Patients: 688 patients visiting their internists' offices were surveyed (response rate, 86%); 88 patients who reported one or more omissions of care on a post-visit questionnaire and were available for a telephone interview 1 to 7 days after the visit were included in the qualitative inquiry. Measurements: Proportion of surveyed patients who reported one or more omissions of care, and qualitative analysis of the sources of patients' expectations, as determined from the telephone interviews. Interviews focused on the sources of expectations and perceptions of omission. Using an iterative process and working by consensus, investigators developed coding categories on a randomly selected 50% of the transcripts. The other 50% of the sample was used for validation. Results: The 125 patients who had unmet expectations perceived omissions that were related to physician preparation for the visit (23%), history taking (26%), physical examination (30%), diagnostic testing (28%), prescription of medication (19%), referral to specialists (26%), and physician–patient communication (15%). Unmet expectations were shaped by patients' current somatic symptoms (intensity of symptoms, functional impairment, duration of symptoms, and perceived seriousness of symptoms) (74%); perceived vulnerability to illness (related to age, family history, personal lifestyle, or previously diagnosed conditions) (50%); past experiences (personal or familial) with similar illnesses (42%); and knowledge acquired from physicians, friends, family, or the media (54%). Conclusions: Patients' expectations for care are derived from multiple sources; their complexity should discourage simple schemes for “demand management.” Nevertheless, the results of this study may help physicians to take a more empathetic stance toward their patients' requests and to devise more successful strategies for clinical negotiation.
The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen
Authors: Seiji Kawamoto, Ali Yalcindag, Dhafer Laouini, Scott Brodeur, Paul Bryce, Bao Lu, Alison A. Humbles, Hans Oettgen, Craig Gerard, Raif S. Geha
Journal: Journal of Clinical Investigation (2004)

Mechanical injury to the skin results in activation of the complement component C3 and release of the anaphylatoxin C3a. C3a binds to a seven-transmembrane G protein–coupled receptor, C3aR. We used C3aR–/– mice to examine the role of C3a in a mouse model of allergic inflammation induced by epicutaneous sensitization with OVA. C3aR–/– mice exhibited an exaggerated Th2 response to epicutaneous but not to intraperitoneal sensitization with OVA, as evidenced by significantly elevated levels of serum OVA-specific IgG1 and significantly increased secretion of the Th2 cytokines IL-4, IL-5, and IL-10 by antigen-stimulated splenocytes. Presentation of OVA peptide by C3aR–/– APCs caused significantly more IL-4 and IL-5 secretion by T cells from OVA–T cell receptor (OVA-TCR) transgenic mice compared with presentation by WT APCs. C3a inhibited the ability of splenocytes, but not of highly purified T cells, to secrete Th2 cytokines in response to TCR ligation. This inhibition was mediated by IL-12 secreted by APCs in response to C3a. These results suggest that C3a-C3aR interactions inhibit the ability of APCs to drive Th2 cell differentiation in response to epicutaneously introduced antigen and may have important implications for allergic skin diseases.
Abstract 2058: Expression of Brain MMP9 in a Rat Model of Cardiopulmonary Resuscitation Treated with SB-3CT
Authors: Zhijie He, Tong Wang, Zitong Huang, Zijun Zou, Xiaotong Chen
Journal: Circulation (2008)

Over-expression of matrix metalloproteinase 9(MPP 9) in brain could degrade extracellular matrix, destroy the structure of microvascular basal membrane and vascular wall, take part in neural- inflammatory response in a rat model of cardiopulmonary resuscitation (CPR). SB-3CT is a antagonist of MPP 9. SB-3CT can inhibit over-expression of MPP 9 and reduce impairment of brain in a rat model of CPR. One hundred and twenty rats were randomly divided into 3 groups: the sham-operated group, the resuscitation control group and the resuscitation treatment group with SB-3CT. The rats were executed and the brains were taken out at 0h, 3h, 9h, 24h and 48h. The expression of MMP 9 in brain was detected. Water content and Evans blue content in brain tissue were observed. The expression of MMP 9 (Table 1 ), water content and Evans blue content in the resuscitation control group was obviously higher than the sham-operated group at 0h, 3h, 9h, 24h and 48h. The expression of MMP 9, water content and Evans blue content in the resuscitation treatment group was similar to the resuscitation control group at different time, but the level was lower than the resuscitation control group(p&lt;0.05). SB-3CT as a specific antagonist of MMP9, could decrease the expression of MMP9 and decrease cerebral edema in a rat model of CPR, and it may be a useful traetment method for cerebral ischemia/reperfusion injury after CPR. Table 1 Expression of brain MMP 9 after resuscitation in a rat model of CPR
Behavioral vs Drug Treatment for Urge Urinary Incontinence in Older Women
Authors: K L Burgio, J L Locher, P S Goode, J M Hardin, B J McDowell, M Dombrowski, D Candib
Journal: JAMA (1998)

Context.—Urinary incontinence is a common condition caused by many factors with several treatment options.Objective.—To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women.Design.—Randomized placebo-controlled trial conducted from 1989 to 1995.Setting.—University-based outpatient geriatric medicine clinic.Patients.—A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia.Intervention.—Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition.Main Outcome Measures.—Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment.Results.—For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P&lt;.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% "much better" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups.Conclusion.—Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.
Reliability of a monitoring system for respiratory emergency room admissions
Authors: F Martinez, J Sunyer, JM Anto
Journal: European Respiratory Journal (1993)

A respiratory emergency room admissions monitoring system (RERAMS) was set up in Barcelona between 1985-1989, in order to investigate asthma epidemics in the city. Information on emergency room admissions for asthma and chronic obstructive pulmonary disease (COPD) was recorded daily from the four main hospitals of the city. The present study aims at assessing the reliability and coverage of this monitoring system. Identification of asthma and COPD emergencies was repeated by a reference observer, following the same protocol to extract data as that used by the register. To assess the coverage of the monitoring system, information was collected over 28 randomly selected days, from the emergency room clinical records for the seven additional hospitals in the city with five or more daily emergencies. Identification of asthma emergencies was highly reliable (kappa value, kappa = 0.81) as was the discrimination between asthma and COPD diagnoses (kappa = 0.91). Reliability for emergencies classified as COPD was lower, but still good (kappa = 0.65). The monitoring system covered 76 and 78% of all Barcelona asthma and COPD emergency room admissions, respectively. Emergency room admissions from our monitoring system did not differ in terms of social and demographic characteristics from emergencies recorded at the other hospitals. We conclude that the monitoring system for the Barcelona respiratory emergency room admissions was highly reliable, which suggests that, when adequately collected, information from clinical records of respiratory emergencies could be used for environmental epidemiological purposes.
Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment
Authors: Morad Bensidhoum, Alain Chapel, Sabine Francois, Christelle Demarquay, Christelle Mazurier, Loic Fouillard, Sandrine Bouchet, Jean Marc Bertho, Patrick Gourmelon, Jocelyne Aigueperse, Pierre Charbord, Norbert Claude Gorin, Dominique Thierry, Manuel Lopez
Journal: Blood (2004)
von Willebrand factor and vascular injury in rheumatoid arthritis.
Authors: B Seriolo, S Accardo, M Cutolo
Journal: Annals of the Rheumatic Diseases (1994)

<h3>Abstract</h3> In the field of artificial intelligence, a combination of scale in data and model capacity enabled by unsupervised learning has led to major advances in representation learning and statistical generation. In biology, the anticipated growth of sequencing promises unprecedented data on natural sequence diversity. Learning the natural distribution of evolutionary protein sequence variation is a logical step toward predictive and generative modeling for biology. To this end we use unsupervised learning to train a deep contextual language model on 86 billion amino acids across 250 million sequences spanning evolutionary diversity. The resulting model maps raw sequences to representations of biological properties without labels or prior domain knowledge. The learned representation space organizes sequences at multiple levels of biological granularity from the biochemical to proteomic levels. Unsupervised learning recovers information about protein structure: secondary structure and residue-residue contacts can be identified by linear projections from the learned representations. Training language models on full sequence diversity rather than individual protein families increases recoverable information about secondary structure. The unsupervised models can be adapted with supervision from quantitative mutagenesis data to predict variant activity. Predictions from sequences alone are comparable to results from a state-of-the-art model of mutational effects that uses evolutionary and structurally derived features.
Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade
Authors: Jacqueline Saw, A.Michael Lincoff, Walter DeSmet, Amadeo Betriu, Wolfgang Rutsch, Robert G. Wilcox, Neil S. Kleiman, Kathy Wolski, Eric J. Topol
Journal: Journal of the American College of Cardiology (2004)