tbuckley/cabot-search huggingface dataset:
Physicians' Awareness and Attitudes Toward Decision Aids for Patients With Cancer
Authors: Chantalle Brace, Selina Schmocker, Harden Huang, J. Charles Victor, Robin S. McLeod, Erin D. Kennedy
Journal: Journal of Clinical Oncology (2010)

Purpose Patient decision aids are interventions designed to help patients make deliberative choices about their treatment options and have been shown to significantly improve patient outcomes. Although considered optimal, decision aids are not widely used in clinical practice for cancer treatment. The objectives of this study are to determine physicians' awareness and use of decision aids, physicians' perceptions of the major barriers to the use of decision aids, and physician characteristics predictive of use of decision aids in clinical practice. Methods A population-based survey was mailed to general surgeons, medical oncologists, and radiation oncologists. Results The survey was mailed to 878 physicians, and the overall response rate to the survey was 64.5%. The majority of the participants were male and working in community hospitals for more than 10 years. Overall, 69% of the respondents were aware of decision aids, and 46% were aware of decision aids relevant to their practice. However, only 24% were currently using decision aids. The main barriers to the use of decision aids were reported as lack of awareness, lack of resources, and lack of time. Multivariate analysis showed specialty to be the only physician characteristic influencing the use of decision aids. Conclusion Approximately one third of physicians treating cancer patients are not aware of what decision aids are, and only 24% are currently using decision aids in clinical practice. Strategies to increase physician awareness about decision aids and to implement these tools into clinical practice are important.
On the in vivo action of erythropoietin: a quantitative analysis
Authors: Thalia Papayannopoulou, Clement A. Finch
Journal: Journal of Clinical Investigation (1972)

The composite response of the erythron to exogenous erythropoietin has been studied in normal, splenectomized, and polycythemic mice. After stimulation the normal animal doubled its marrow nucleated red cells by the 3rd day with little further change by the 5th. Nucleated red cells within the spleen began to increase sharply on the 2nd day and, by the 5th, exceeded those in the marrow. The total nucleated erythroid response represented a fourfold increase. Reticulocytes lagged behind the expansion of the nucleated red cell mass, but by the 5th day the original ratio was re-established. Hemoglobin synthesis was increased, but the ratio of hemoglobin synthesized in nucleated red cells and reticulocytes was basically unchanged. Early displacement of marrow reticulocytes into circulation and the production of a larger red cell also occurred. No evidence of a change in the number of erythroid mitoses was found; only a slight decrease in the average cell cycle time was demonstrated. Thus, whereas erythropoietin stimulation induced several changes in erythropoiesis, the increased number of cells entering into the maturing pool appeared to be of greatest quantitative significance.Splenectomy reduced the proliferative response of the erythron over 5 days stimulation to three-fourths that found in the normal animal. This difference, also reflected in a proportionately lower reticulocyte response and increment in circulating red cell mass, suggests that erythropoiesis within the mouse marrow is spatially or otherwise restricted and that the spleen provided a supplemental area of erythroid expansion.
1083. Systemic rAAV-CB-IL-10 Expression and Its Long Term Effects on CD4+CD25+ T Cell Populations
Authors: Christian Muller, Sofia A. Braag, Ashley Martino, Mark A. Atkinson, Terence R. Flotte
Journal: Molecular Therapy (2005)

Top of pageAbstract
Recently, it has been highlighted that the generation of CD4+CD25+ T-regulatory cells in vitro relies heavily on the presence of IL-10. These cells are capable of resolving and preventing autoimmunity and inflammatory processes. These properties make IL-10 gene therapy an attractive candidate therapy for a wide range of inflammatory diseases from autoimmune diabetes to the airway inflammatory processes observed in the CF airways. Our group has already published data showing the utility of a recombinant adeno-associated virus (rAAV) vector expressing IL-10 from the CMV enhancer/beta actin promoter hybrid (rAAV-CB-IL10). Due to the potential for IL-10 to be immunosuppressive at higher levels, it is important to optimize the dose of rAAV-CB-IL-10 vector to be used in order to obtain the desired effects.  

C57Bl/6 were injected with rAAV1-pseudotyped-CB-IL-10 in the gastrocnemius muscle with 7.0|[times]|109 (low dose n=3), 1.4|[times]|1010 (medium dose n=3) and 2.8|[times]|1010 (high dose n=3) vector genomes. Serum IL-10 levels were monitored at 0, 1, 2, 3, 4, 8, 12, 16 and 40 weeks post-injection. Mice were sacrificed 40 weeks after rAAV i.m. injection. Blood was collected for cell blood counts (CBC) and splenocytes were harvested for flow cytometry.Serum IL-10 levels were detected as early as 1-week after injection and stabilized at 2 months post injection. Average levels of serum IL-10 after stabilization were 51 pg/ml (low dose), 232 pg/ml (medium dose) and 1035 pg/ml (high dose). CBC revealed low platelet levels (128 K/ul normal range 592|[ndash]|2972 K/ul) and low hemoglobin levels in the high dose animals. Interestingly, splenocyte analysis for CD4+CD25+ T cells revealed a clear difference in the percentage of T regulatory cells present among the three groups. When the serum IL-10 levels for individual mice are plotted against % of CD4+CD25+ T cells, mice with levels lower than 200 pg/ml have populations between 10-13% of CD4+CD25+ T cells while mice above 200 pg/ml have populations in the range of 18-22%. No additional advantage in T-regulatory cell generation was observed at the highest dose.

From these preliminary studies we have determined that the difference in the % of CD4+CD25+ T cells population is greater in mice that average levels higher than 200 pg/ml. The percentages of these population is not significantly different past this threshold however there are undesirable effects at the higher systemic IL-10 levels (1000|[ndash]|1500pg/ml). The CBC data showed mice in the high dose group had anemia and thromocytopenia. Thus, for future studies serum IL-10 levels between 200 and 1000 pg/ml are optimal. This provides benefits both from the anti-inflammatory effects exerted by IL-10 and the increase in Treg cells without having undesirable side effects observed at the higher doses.
All liver recipients benefit from the protocol 10-year liver biopsies
Authors: Mylène Sebagh, Kinan Rifai, Cyrille Féray, Funda Yilmaz, Bruno Falissard, Bruno Roche, Henri Bismuth, Didier Samuel, Michel Reynès
Journal: Hepatology (2003)

The value of late protocol biopsies after liver transplantation remains to be evaluated to highlight the therapeutic policies. The study population was composed of patients who survived with the initial graft and with an available 10-year protocol biopsy (n = 143). The long-term histologic outcome of the graft, particularly the rate of ductopenia in cases with chronic rejection (CR), and Metavir scoring of fibrosis in cases with viral chronic hepatitis (VCH), were assessed. Fibrosis progression (FP) rates were compared over 3 periods (0-5, 5-10, and 0-10 years). At 10 years, histologic abnormalities present in 80% of the patients were not identifiable from liver function tests (LFTs), which were strictly normal in 52% of the patients. Histologic CR occurred in 24% at 10 years, with a mean rate of ductopenia higher at 10 years than at 5 years (49% vs. 34%, P <.001). In cases of VCH, fibrosis worsened, with a median FP rate of 0.20 fibrosis units/year. During the first 5 years, FP was as follows; hepatitis B virus infection was greater than recurrent hepatitis C virus (HCV) infection, which was greater than acquired HCV infection (P =.029). In patients with HCV, FP was higher during the second 5-year period than during the first one (P =.042). In conclusion, given the high prevalence of histologic abnormalities and the lack of sensitivity and specificity of LFTs, late protocol biopsies clearly are justified to adjust treatments, not only in HCV-infected patients in whom FP was fast and not linear, but also in the whole population of recipients.
Chronic Active Hepatitis in Hepatitis B Surface Antigen (HBsAg) Carriers
Authors: Richard Sampliner
Journal: JAMA (1977)

Four cases of chronic active hepatitis were found in hepatitis B surface antigen (HBsAg) positive blood donors. Despite minimal symptoms, the full histologic spectrum of chronic hepatitis was seen. Because clinically occult liver disease can be histologically severe, liver biopsy is indicated when liver enzyme levels are persistently abnormal in long-term HBsAg carriers.
Abstract 3725: Anti-DLL4 (demcizumab) inhibits tumor growth and reduces cancer stem cell frequency in patient-derived ovarian cancer xenografts.
Authors: Wan-Ching Yen, Marcus M. Fischer, Jalpa Shah, Jie Wei, Jennifer Cain, Pete Yeung, Lucia Beviglia, Belinda Cancilla, Ann Kapoun, John Lewicki, Austin Gurney, Timothy Hoey
Journal: Cancer Research (2013)

Abstract Ovarian cancer in a major cause cancer related death in women and this disease is often characterized by resistance to chemotherapy and tumor recurrence. Cancer stem cells (CSCs) have been shown to be relatively insensitive to chemotherapeutic agents. Several lines of evidence indicate that aberrant Notch signaling plays a major role in ovarian cancer progression and resistance to standard therapies. DLL4 is a key ligand that activates the Notch pathway and has been shown to regulate both CSC function and tumor angiogenesis. DLL4 expression in tumor and endothelial cells has also been associated with resistance to bevacizumab treatment. In these studies, we investigated the role of anti-DLL4 in a panel of patient-derived ovarian cancer xenograft models. We utilized anti-human DLL4 (OMP-21M18) and anti-murine DLL4 to block Notch signaling in both the tumor and stromal/vascular cells in the xenografts. We found that anti-DLL4 treatment was broadly efficacious in these ovarian cancer models, significantly inhibiting tumor growth both as a single agent and in combination with paclitaxel. We carried out serial transplantation studies to investigate the effect on cancer stem cells and found that anti-DLL4 in combination with paclitaxel profoundly reduced the tumor initiating cell frequency. In contrast, treatment with paclitaxel alone had the opposite effect and increased ovarian CSC frequency. These data suggest that anti-DLL4 treatment sensitizes chemoresistant ovarian tumorigenic cells to therapy and provide compelling evidence that anti-DLL4 (demcizumab) is a promising strategy for the clinical treatment of ovarian cancer. Citation Format: Wan-Ching Yen, Marcus M. Fischer, Jalpa Shah, Jie Wei, Jennifer Cain, Pete Yeung, Lucia Beviglia, Belinda Cancilla, Ann Kapoun, John Lewicki, Austin Gurney, Timothy Hoey. Anti-DLL4 (demcizumab) inhibits tumor growth and reduces cancer stem cell frequency in patient-derived ovarian cancer xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3725. doi:10.1158/1538-7445.AM2013-3725
Effect of abortion on obstetric patterns.
Authors: R Beard, D B Paintin
Journal: BMJ (1977)

The statement of A.F. Pentecost that "it is an established fact that 1 or more terminations of pregnancy are liable to result in more women coming in at 26 weeks with ruptured membranes" needs to be challenged. The study he quotes to support his view indicates that 7 out of 8 women who had premature rupture of the membranes had previously been aborted of pregnancies exceeding 10 weeks' gestation and most likely with the traumatic techniques in use at that time. In the 1960s Hegar dilators of larger than Size 12 were used in the majority of cases, and dilation to such a degree was likely to result in frequent damage to the internal os, causing subsequent cervical incompetence and premature rupture of the membranes. However, the modern aspiration techniques now in use rarely require the cervix to be dilated to more than Hegar 10. Consequently, subsequent premature labor because of cervical incompetence is unlikely. Evidence is frequently quoted from a number of papers in support of Mr. Pentecost's position. It does not seem possible that a clinical trial will ever be conducted that will finally resolve the issue because of the problem of obtaining matched controls, difficulties of follow-up, and variable abortion techniques. Available evidence does indicate that modern legal abortion generally increases the risks of prematurity in a subsequent pregnancy. The remaining question is whether the reduction in the incidence of low birth weight can be ascribed to legal abortion.
Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein.
Authors: W Rottbauer, M Gautel, J Zehelein, S Labeit, W M Franz, C Fischer, B Vollrath, G Mall, R Dietz, W Kübler, H A Katus
Journal: Journal of Clinical Investigation (1997)

Familial hypertrophic cardiomyopathy is a disease generally believed to be caused by mutations in sarcomeric proteins. In a family with hypertrophic cardiomyopathy linked to polymorphic markers on chromosome 11, we found a new mutation of a splice donor site of the cardiac myosin-binding protein-C gene. This mutation causes the skipping of the associated exon in mRNA from lymphocytes and myocardium. Skipping of the exon with a consecutive reading frame shift leads to premature termination of translation and is thus expected to produce a truncated cardiac myosin-binding protein-C with loss of the myosin- and titin-binding COOH terminus. However, Western blot analysis of endomyocardial biopsies from histologically affected left ventricular myocardium failed to show the expected truncated protein. These data show for the first time that a splice donor site mutation in the myosin-binding protein-C gene is transcribed to cardiac mRNA. Truncated cardiac myosin-binding protein-C does not act as a "poison polypeptide," since it seems not to be incorporated into the sarcomere in significant amounts. The absence of mutant protein and of significantly reduced amounts of wild-type protein in the presence of the mutated mRNA argues against the "poison protein" and the "null allele" hypotheses and suggests yet unknown mechanisms relevant to the genesis of chromosome-11- associated familial hypertrophic cardiomyopathy.
Spontaneous Closure of Vesicouterine Fistula Following Cesarean Section
Authors: Robert J. Rauch
Journal: JAMA (1962)

A VESICOUTERINE FISTULA may be defined as an abnormal communication between the bladder and uterine cavity above the level of the cervical internal os, which allows the menstrual blood to enter the bladder and causes cyclic hematuria. Normal menstruation and leakage of urine from the vagina are usually absent. Figure 1 demonstrates the anatomy of this type of fistula as compared with the other more common genitourinary fistulas. Only 8 cases of vesicouterine fistula have been described in the world literature to date, probably because this condition is almost always a complication of the lower-segment type of cesarean section which has been popular in only the past 25 years. This is the first case report of a vesicouterine fistula that closed spontaneously.  Report of a Case  A 25-year-old, primigravid, clinic patient was admitted to the Lenox Hill Hospital labor ward on Nov. 21, 1958, at term and in early labor.
SPEECH IN SENILITY
Authors: FRED FELDMAN, D. EWEN CAMERON
Journal: American Journal of Psychiatry (1944)

The speech of psychotic senile patients was analyzed grammatically, and compared with that of normal adults and children. Pronouns, verbs and adjectives display the most prominent differences between the senile and the normal subjects. Pronouns are used relatively more often in seniles, verbs also more often, and adjectives less frequently. The implications of these differences are discussed.
Abstract B18: Blocking α4β1 integrin interaction with matrix metalloproteinase-9 overcomes stroma-induced resistance of chronic lymphocytic leukemia cells to fludarabine and arsenic trioxide
Authors: Irene Amigo-Jiménez, Elvira Bailón, Estefanía Ugarte-Berzal, José Antonio García-Marco, Angeles Garcia-Pardo
Journal: Cancer Research (2015)

Abstract Chronic lymphocytic leukemia (CLL) progression is determined by CLL cell accumulation in lymphoid organs, where they receive survival signals that impair therapeutic treatments. MMP-9 is a microenvironment component and we have shown that induces a signalling pathway that leads to CLL cell survival. We have now studied whether MMP-9 is involved in the response to cytotoxic agents such as fludarabine and arsenic trioxide (ATO). Both agents upregulated MMP-9 (mRNA and protein) and enhanced its binding to CLL cells. Cell-associated MMP-9 was restricted to early apoptotic cells and totally dependent on apoptosis onset, suggesting a role in the response to these drugs. Indeed, anti-MMP-9 antibodies accelerated apoptosis. Moreover, MEC-1 cells (CLL-derived) stably transfected with MMP-9 were more resistant to drug-induced apoptosis than Mock-transfected cells. Western blot analyses revealed that MMP-9 prevented down regulation of anti-apoptotic Bcl-2 family members. Therefore, MMP-9 likely represents a compensatory survival response that contributes to drug resistance. Additionally, culturing CLL cells with bone marrow stromal cells (BMSC) prevented the apoptotic effect of ATO and this was nearly completely reverted with anti-MMP-9 antibodies. Blocking α4β1 integrin (MMP-9 receptor) and/or αLβ2 integrin (ICAM-1 receptor) also overcame stroma-induced survival. This was also partially achieved by culturing CLL cells with BMSC-conditioned medium, indicating that both cell adhesion and soluble factors contributed to the observed drug resistance. To determine the mechanisms involved, the effect of blocking several signalling pathways was studied. Inhibiting the PI3K/Akt or focal adhesion pathways with specific inhibitors significantly restored the sensitivity of CLL cells to ATO. Therefore, our results highlight the role of MMP-9 in CLL drug resistance and indicate that concomitant targeting of MMP-9 may improve the CLL response to treatment. Supported by grants SAF2012-31613 and RD12/0036/0061 (AGP) from the Ministry of Economy and Innovation, Spain; S2010/BMD-2314 (AGP) from the Comunidad de Madrid/European Union, and by a grant from the Fundación Puerta de Hierro, Madrid (JAGM). Citation Format: Irene Amigo-Jiménez, Elvira Bailón, Estefanía Ugarte-Berzal, José Antonio García-Marco, Angeles Garcia-Pardo. Blocking α4β1 integrin interaction with matrix metalloproteinase-9 overcomes stroma-induced resistance of chronic lymphocytic leukemia cells to fludarabine and arsenic trioxide. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B18. doi:10.1158/1538-7445.CHTME14-B18
Effect of β-adrenergic receptor blockade or refractoriness induced by isoproterenol on growth of keratinocytes in virto
Authors: ELAINE K. ORENBERG, DAVID I. WILKINSON
Journal: British Journal of Dermatology (1982)

Almost complete suppression of beta-adrenergic sensitivity of adenylate cyclase was produced in keratinocytes growing on collagen gels either by induction of refractoriness by isoproterenol or by receptor blockade by propranolol, these drugs being introduced 3 days post-plating and continuously thereafter. Neither of these two manoeuvres affected growth of the keratinocytes. Despite this suppression, basal levels of cyclic AMP never fall below the levels observed in untreated cultures. On the other hand, growth inhibition is observed if isoproterenol or propranolol is added on plating. When keratinocytes are seeded on 3T3 fibroblast feeder layers, isoproterenol enhances colony growth, as reported elsewhere, indicating that the effects of isoproterenol are therefore modulated by the culture surface. In either of these in vitro model systems studied (collagen or feeder layers), no mechanism was obvious that would account for propranolol-induced psoriasiform lesions observed in vivo.
EFFECTS OF EVOLOCUMAB (AMG 145) IN HYPERCHOLESTEROLEMIC, STATIN-TREATED, JAPANESE PATIENTS AT HIGH CARDIOVASCULAR RISK: RESULTS FROM THE PHASE III YUKAWA 2 STUDY
Authors: Arihiro Kiyosue, Narimon Honarpour, Allen Xue, Scott Wasserman, Atsushi Hirayama
Journal: Journal of the American College of Cardiology (2015)
Angiosarcomatosis A Rare Cause of Gastrointestinal Bleeding Diagnosed By Tc-99m Labeled Red Cell SPECT
Authors: DAVID J. MACFARLANE, FREDERICK A. KHAFAGI, DENIS GRIBBIN, CLAIRE REINHART, PHILIP J. STOREY
Journal: Clinical Nuclear Medicine (1995)

The initial examination of a 75-year-old woman with lethargy and malaise led to the resection of a 1300 g benign ovarian teratoma with focus of struma ovarii. A small focus of angiosarcoma was seen within omentum attached to the pelvic tumor. The patient suffered recurrent melena and hematochezia, with no bleeding focus seen on gastrointestinal endoscopy. A Tc-99m labeled red cell Gl bleeding study with SPECT demonstrated multiple abnormal Intra-abdominal accumulations of red cells, without evidence of active bleeding. Only one of these was apparent on abdominal CT. Mesenteric angiography confirmed the presence of vascular malformations consistent with angiosarcoma.
The illicit drug scene.
Authors: T Bewley
Journal: BMJ (1975)

Drug taking is probably not in itself a social or medical problem or a cause of such problems, and most drug takers never come to the notice of official agencies. The minority who constitute a problem may be involved with drug taking for complex or psychological reasons; they may be relying on drugs until alternative support becomes available. The commonest illicit drug is cannabis. Others include lysergide (LSD), which like cannabis is obtained wholly from unlawful sources. Amphetamines (and other central nervous stimulants) and barbiturates (and other central nervous de pressants) are also taken illicitly though their source originally may have been legitimate for example, they may have been stolen from pharmacies or overprescribed by doctors. Finally, opiates may find their way on to the black market from diversion of prescribed drugs on the one hand to smuggling of Chinese heroin on the other.
The History and Advances of Reversible Terminators Used in New Generations of Sequencing Technology
Authors: Fei Chen, Mengxing Dong, Meng Ge, Lingxiang Zhu, Lufeng Ren, Guocheng Liu, Rong Mu
Journal: Genomics Proteomics & Bioinformatics (2013)

Abstract DNA sequencing using reversible terminators, as one sequencing by synthesis strategy, has garnered a great deal of interest due to its popular application in the second-generation high-throughput DNA sequencing technology. In this review, we provided its history of development, classification, and working mechanism of this technology. We also outlined the screening strategies for DNA polymerases to accommodate the reversible terminators as substrates during polymerization; particularly, we introduced the “REAP” method developed by us. At the end of this review, we discussed current limitations of this approach and provided potential solutions to extend its application.
Myocardial Performance Index and Aortic Distensibility in Patients with Different Left Ventricle Geometry in Newly Diagnosed Essential Hypertension
Authors: Durmuş Yıldıray Şahin, Mustafa Gür, Zafer Elbasan, Gülhan Yüksel Kalkan, İbrahim Özdoğru, Ali Kıvrak, Gökhan Gözübüyük, Osman Kuloğlu, Zehra Sümbül, Murat Çaylı
Journal: Journal of the American College of Cardiology (2013)