tbuckley/cabot-search huggingface dataset:
Abstract 4918: Modeling polymersome delivery of anticancer therapeutics
Authors: Ian Sorrell, Steven D. Webb, Rebecca J. Shipley, Vanessa L. Hearnden, Helen E. Colley, Craig Murdoch
Journal: Cancer Research (2012)

Abstract Polymersomes are synthetic nano-spheres that have the potential to specifically deliver anticancer therapeutics to tumor cells. They are an ideal delivery vector because of their nanometer size, structural architecture, stealth characteristics and the ability to attach tumor-specific ligands to their outer surface. The possible benefits of targeted polymersome drug delivery include reduced off-target toxic effects in healthy tissue and increased drug uptake by diseased tissue. In this study, in vitro experimentation is used to validate a mathematical description of polymersome-mediated therapy. Mathematical predictions are given for how the properties of polymersomes (size, membrane properties) and drug load affects rates of polymersome internalisation by tumor cells and therefore treatment efficacy. This allows for an optimisation of treatment design prior to clinical development. A key focus is polymersome-drug delivery via the clathrin-mediated endocytotic pathway. We include in our theoretical description specific details of this process (including specific binding ligands, receptor clustering, ligand tether length) and show how the characteristics of receptor targeting, number of ligands per polymersome, and polymersome concentration alters its uptake by tumor cells. The theoretical model is validated against in vitro studies using polymersome drug delivery to cell monolayers derived from different tumors. Next we describe how to scale-up the model to a tissue representation of the tumor mass. In this description the concentration of solutes (including oxygen and polymersomes) are tracked throughout the tumor using computational models based on realistic tumor vascular network structures with associated blood flow that have been constructed from confocal microscopic observations of a xenograft sub-cutaneously implanted tumor. Our results quantify the dependence of polymersome uptake rate and tumor distribution on polymersome properties and dosage. This multiscale approach identifies the key polymersome properties that influence treatment outcome and enables the treatment regime to be designed specifically in response to these features. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4918. doi:1538-7445.AM2012-4918
Human In Vitro Fertilization-Reply
Authors: Hans O. Tiefel
Journal: JAMA (1982)

In Reply.—  The argument of possible risk is central for the ethics of in vitro fertilization. The low success rate of implantations and the high rate of spontaneous abortions, compared with natural pregnancies, are causes for worry. Comparing children born by this method with those conceived traditionally cannot be scientifically done for some time, according to cited statistical rules. More important, this procedure experiments with future lives, and there is no way of proving it safe without such experimental risk. I argue that risk should be undertaken only for oneself or when it is unavoidable for helping human beings. We should not conceive when there is an increased chance for harm.  It is true that parents have ample reason for feeling guilty. But why add to those reasons? The evidence here lies in considering oneself in place of parents with seriously ill children who were technologically conceived. If exposure to
Trends in Antihypertensive Medication Use and Blood Pressure Control Among United States Adults With Hypertension
Authors: Qiuping Gu, Vicki L. Burt, Charles F. Dillon, Sarah Yoon
Journal: Circulation (2012)

Background— The monitoring of national trends in hypertension treatment and control can provide important insight into the effectiveness of primary prevention efforts for cardiovascular disease. The objective of this study was to examine recent trends in antihypertensive medication use and its impact on blood pressure control among US adults with hypertension. Methods and Results— A total of 9320 hypertensive people aged ≥18 years from the National Health and Nutrition Examination Survey 2001 to 2010 were included in this study. The prevalence of antihypertensive medication use increased from 63.5% in 2001 to 2002 to 77.3% in 2009 to 2010 ( P trend &lt;0.01). Most notably, there was a large increase in the use of multiple antihypertensive agents (from 36.8% to 47.7%, P trend &lt;0.01). Overall, the use of thiazide diuretics, β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers increased by 23%, 57%, 31%, and 100%, respectively. In comparison with monotherapy, single-pill combinations and multiple-pill combinations were associated with 55% and 26% increased likelihoods of blood pressure control, respectively. By the 2009 to 2010 time period, 47% of all hypertensive people and 60% of treated hypertensive people had blood pressure controlled. However, higher treated but uncontrolled hypertension rates continued to persist among older Americans, non-Hispanic blacks, diabetic people, and those with chronic kidney disease. Also, Mexican Americans with hypertension were still less likely to take antihypertensive medication than non-Hispanic whites with hypertension. Conclusions— Antihypertensive medication use and blood pressure control among US adults with hypertension significantly increased over the past 10 years. Combination therapy regimens can facilitate achievement of blood pressure goals.
COMPARISON OF ARTERIAL REPAIR FOLLOWING EVEROLIMUS- AND SIROLIMUS-ELUTING STENT IMPLANTATION IN PATIENTS: A MULTICENTER ANGIOSCOPIC STUDY
Authors: Masaki Awata, Fusako Sera, Takayuki Ishihara, Masashi Fujita, Tetsuya Watanabe, Osamu iida, Yoshiaki Mitsutake, Takafumi Ueno, Shinsuke Nanto, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2012)
Low membrane protein sulfhydrils but not G6PD deficiency predict ribavirin-induced hemolysis in hepatitis C
Authors: Ignazio Grattagliano, Stefan Russmann, Vincenzo O. Palmieri, Peter Jüni, Florian Bihl, Piero Portincasa, Giuseppe Palasciano, Bernhard H. Lauterburg
Journal: Hepatology (2004)

Hemolysis is a frequent adverse effect of ribavirin (RBV). It has been suggested that oxidative stress plays a role, but mechanisms and predictive risk factors for severe forms remain unknown. Markers of redox status were determined in erythrocytes of 34 patients with hepatitis C—four of them with glucose-6-phosphate-dehydrogenase (G6PD) deficiency—before and during treatment with RBV and interferon (IFN) and were compared with 10 healthy control subjects. In addition, erythrocytes were incubated with RBV, and the effects of dipyridamole (DPD), diethylmaleate (DEM), and glutathione ester (GSHE) were studied in vitro . Of the 30 patients without G6PD deficiency who were treated with RBV and IFN-α, five developed major hemolysis (Δ hemoglobin &gt; 6 g/dL) and 25 developed minor hemolysis (Δ hemoglobin &lt; 2.5 g/dL). Patients with major hemolysis had lower median pretreatment values of membrane protein sulfhydrils than patients with minor hemolysis (28.4 vs. 36.7 nmol/mg, P &lt; .001). Erythrocytes of G6PD-deficient patients were not more susceptible to RBV-induced hemolysis. In in vitro incubations of erythrocytes, DEM enhanced the RBV-induced decrease of glutathione, protein sulfhydrils, and osmotic resistance. Supplementation of GSHE and DPD prevented the RBV-induced decrease in osmotic resistance, adenosyl triphosphate (ATP), and 2,3-diphosphoglycerate (DPG), the loss of glutathione and protein sulfhydrils, and the formation of thiobarbituric acid reactive substances (TBARs). In conclusion, the data indicate that low membrane protein sulfhydrils prior to therapy but not G6PD deficiency are predictive of RBV-induced major hemolysis. In vitro , GSHE and DPD reduce the RBV-associated oxidative stress in erythrocytes and prevent the increase in osmotic fragility, suggesting that these compounds might decrease the risk of hemolysis in patients. (Hepatology 2004;39:1248-1255.)
Placing Religion and Spirituality in End-of-Life Care
Authors: Timothy P. Daaleman, Larry VandeCreek
Journal: JAMA (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
FEBRILE ACIDOSIS IN SCARLET FEVER IN CHILDREN
Authors: R. E. Thomas
Journal: BMJ (1919)

ACETONURIA has been found by Harris in 84.8 per cent. of cases of scarlet fever in children.'I have examined daily the urine of seven consecutive cases with moderate aittacks, estimating the acidity, the proportion of urea and ammonia-amnido nitrogen, and testing for acetone and diacetic acid, with the following, results:1. Acidosis lasting from three to twelve days, reaclhing its maximum on the third to fifth day of disease.2. Acetone and diacetic acid not always, though genaerally, present.J. Urine not alkaline duriing administration of sodiun
Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot–Marie–Tooth disease type 1B
Authors: Tanja Kulkens, Pieter A. Bolhuis, Ruud A. Wolterman, Stephan Kemp, Saskia te Nijenhuis, Linda J. Valentijn, Gerard W. Hensels, Frans G.I. Jennekens, Marianne de Visser, Jessica E. Hoogendijk, Frank Baas
Journal: Nature Genetics (1993)
Delirium in older adults
Authors: E. I. O. Vidal, P. J. F. Villas Boas, A. P. Valle, A. T. A. R. Cerqueira, F. B. Fukushima
Journal: BMJ (2013)

The daughter of an 80 year old woman with severely impaired vision from age related macular degeneration and diabetic retinopathy brought her mother to her primary care doctor, as she had been more apathetic and rejecting her meals in the past few days. Her daughter said there were times during the day when her mother looked almost her usual self, yet other times when she was confused and did not seem to be herself. Her doctor diagnosed delirium and referred the patient for assessment at the local emergency department.

Delirium is a neuropsychiatric syndrome characterised by disturbances of cognition, attention, consciousness, or perception that develop over a short period of time (hours to days) with a fluctuating course.1 2 It usually results from the interaction of several precipitating factors (such as drugs, infections, metabolic disturbances, and myocardial infarction) and predisposing factors (such as old age, dementia, and multiple comorbidities).2 There are three subtypes of delirium, according to its psychomotor features: hyperactive, hypoactive, and mixed.

#### How common is delirium?

The fluctuating nature of the symptoms of delirium, its frequent …
In-hospital deaths as fraction of all deaths within 30 days of hospital admission for surgery: analysis of routine statistics
Authors: M. J Goldacre
Journal: BMJ (2002)

Death rates after surgical care are increasingly analysed to estimate prognosis and for clinical audit and quality assessment.Expectations are growing among health professionals and the public that hospitals will know about, and learn from, the death rates of their patients.However, routine statistics commonly provide information only on deaths that occur during the hospital admission in which surgery was done.Rates based on these deaths are conventionally known as in-hospital death rates and are typically analysed as those that occur within 30 days after admission or surgery.Systems of national hospital statistics in England were designed in the 1960s and redesigned in the mid-1980s. 1 2Hospital statistics are not linked to death certificate data nationally, although this has long been feasible. 3 4Even the National Confidential Enquiry into Perioperative Deaths, a meticulous ongoing national study with local clinical reporting and case note review of deaths, is constrained practically to the identification of deaths in the hospital admissions in which the operations were done. 5By using hospital data linked to death certificate data, we studied the extent to which in-hospital deaths accounted for all deaths within 30 days of hospital admissions during which operations were done.
Blood Pool Imaging of Portosystemic Collaterals
Authors: RICHARD C. CORY, L HABELSON WILF
Journal: Clinical Nuclear Medicine (1993)

Tc-99m tagged RBC SPECT imaging has been proven a sensitive means of detecting portosystemic venous collaterals in patients with cirrhosis and portal hypertension. Presented is a case of a 54-year-old man with a history of long-term alcohol abuse, cirrhosis with portal hypertension, and other complications. A Tc-99m–tagged RBC SPECT examination, performed to evaluate the liver for a cavernous hemangioma, demonstrated a tortuous, dilated umbilical vein and multiple dilated superficial paraumbilical veins: caput medusae.
IS IT FAIR? A STUDY OF THE COMPARATIVE POLITICAL POSITION OF THE MEDICAL PROFESSION IN THE UNITED STATES.
Authors: CHARLES MCINTIRE
Journal: JAMA (1883)

[Read before the American Academy of Medicine at its annual meeting October 9, 1883.] In this paper the assumption is made from the start that medicine has an equal claim with theology and law, to be classed among the learned professions. That this assumption may note be deemed presumption on the part of a physician, let us hear the testimony of others. In the<i>Boston Medical and Surgical Journal</i>of the present year (pp. 108-590) there is a report of the annual banquet of the Massachusetts Medical Society. On that occasion B. A. Gould, PH.D., Gött., Director of the Astronomical Observatory of the Argentine Republic, is reported to have said: “The medical was the first of the learned professions. If there was but one learned profession it would not be that of theology, for our consciences lead us to adore and reverence; nor could it be the law; but it
Growth of the great vessels in the normal human fetus and in the fetus with cardiac defects.
Authors: P C Ursell, J M Byrne, T R Fears, B A Strobino, W M Gersony
Journal: Circulation (1991)

BACKGROUND There is a paucity of quantitative anatomic data regarding human great vessel development that could be useful as a reference for fetal echocardiographers who must distinguish abnormal from normal cardiac development at early stages. METHODS AND RESULTS To determine normal growth patterns, we plotted the diameters of the aortic and pulmonary valves, ductus arteriosus, aortic isthmus, and descending aorta in 274 autopsy specimens from nonselected spontaneous abortuses of normal karyotype. There was a linear increase in the diameters of these structures within the developmental period studied (10-26 weeks). A relative narrowing of the aorta at the isthmus compared with the aortic valve and descending aorta probably indicates that the majority of fetal left heart output goes to the developing heart and brain. In contrast to previous studies of late gestation and neonatal animals, however, we found that the diameter of the aortic isthmus was larger than that of the ductus arteriosus, suggesting substantial isthmic blood flow in these midtrimester fetuses. Among nineteen other hearts with diverse defects, both of two hearts with a narrow isthmus had an enlarged ductus arteriosus and one heart with pulmonary atresia/intact septum had a narrow ductus and increased aortic valve diameter. CONCLUSIONS During midgestation, the normal heart may have substantial aortic isthmic blood flow that diminishes due to rerouting in late gestation when increased requirements of the fetal brain and other organs prevail. Although fetal shunts may explain some vessel abnormalities, the majority of cardiac defects in this study were not associated with abnormal growth of the great vessels within this developmental age range.
IDH1 MUTATIONS AS A IMMUNOTHERAPEUTIC TARGET FOR BRAIN TUMORS
Authors: G. E. Archer, E. Reap, P. Norberg, X. Cui, R. Schmittling, J. Herndon, V. Chandramohan, K. Riccione, C.-T. Kuan, H. Yan, D. D. Bigner, J. H. Sampson
Journal: Neuro-Oncology (2014)

BACKGROUND: Immunotherapy promises an exquisitely precise therapeutic approach, and substantial evidence suggests that activated T cells can eradicate large tumors, even within the “immunologically privileged” brain. EGFRvIII and isocitrate dehydrogenase 1 (IDH1) mutations are two of the only consistent tumor-specific mutations that have been described. IDH1 is an evolutionarily-conserved enzyme essential to cell function. Greater than 90% of all IDH1 mutations occur from a substitution of histidine for arginine at codon 132, resulting in the highly conserved and tumor-specific mutation, IDH1R132H. IDH1R132H is homogeneously expressed in all tumor cells in tumors that express this mutation, including single infiltrating tumor cells but is absent in normal cells. The high frequency, specificity, and homogeneous expression of the IDH1 mutation make it an ideal target for therapeutic intervention. METHODS: To assess IDH1R132H as an immunotherapeutic target, we have developed a series of peptides of various lengths that span the IDH1R123H mutation and that are homologous in mice and humans. The murine homologue of IDH1R123H was cloned and transfected into murine glioma lines to be used as a therapeutic target. For immunogenicity experiments mice received 3 weekly intradermal immunizations with 100 µg of peptide. One week following the third vaccination spleen cells were analyzed for interferon gamma (IFN-γ) production by ELISPOT. Adjuvants investigated included CFA/IFA/IFA, IFA x3, IFA + GM-CSF, and IFA x3 following pretreatment with Imiquimod. For efficacy experiments C57BL/6 mice received three i.d. vaccinations with PEPIDH1M in IFA every seven days or no treatment. Seven days after the third vaccination, mice received IC implantation of 5x104 IDH1R132H positive KR158B tumor cells. RESULTS: Lymphocytes from mice immunized with peptides of various lengths containing the IDH1R123H mutation produced IFN-γ by ELISPOT in response to stimulation with the mutant peptide, PEPIDH1M but not wild type. This was true for four different strains of mice and transgenic HLA-A2 mice. The 25mer PEPIDH1M induced the most robust immune response. Lymphocytes derived from PEPIDH1M immunized mice co-cultured with IDH1R132H positive glioma secrete significantly higher levels of IFN-γ than lymphocytes co-cultured with IDH1R132H negative tumor cells. Mice immunized with the 25mer PEPIDH1M mixed with GM-CSF or after treating the skin site with Imiquimod produce a greater IFN-γ response to PEPIDH1M alone. Mice immunized with 25mer PEPIDH1M and challenged 7 days later with KR158B-IDH1R132H tumors showed a statically significant increase in median survival (P = 0.0385, Wilcoxon). CONCLUSIONS: The 25mer PEPIDH1M is capable of inducing a therapeutically effective immune response against intracranial tumors. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
Liver Transplantation: The Cambridge— King's College Hospital Experience
Authors: Robert McCabe
Journal: JAMA (1984)

Replacement therapy, either with transplants or artificial prosthetic devices, offers a gift of life to those with end-stage debilitating diseases. For the many with primary liver cancer, congenital metabolic deficiency, or acquired parenchymatous liver disease, a liver transplant is the only hope. With the advent of cyclosporine immunosuppression, Roy Y. Calne reports that there is now "obviously a worldwide need for liver grafting," which has been developed and performed in only four centers until recently. For those interested in the development of new programs, Professor Calne has edited, in classic British style,<i>Liver Transplantation</i>, the first and currently only such extensive work to my knowledge devoted to liver grafting. The material presented is a compilation of the broad experiences and research from four pioneering centers—Addenbrooke's Hospital, Cambridge, England, with the Liver Unit, Kings College Hospital, London; Groningen in Sweden; Hannover in West Germany; and our own unit under Tom Starzl,
Predicting Deep Venous Thrombosis in Pregnancy: Out in “LEFt” Field?
Authors: Wee-Shian Chan, Agnes Lee, Frederick A. Spencer, Mark Crowther, Marc Rodger, Tim Ramsay, Jeffrey S. Ginsberg
Journal: Annals of Internal Medicine (2009)

Background: Clinicians' assessment of pretest probability, based on subjective criteria or prediction rules, is central to the diagnosis of deep venous thrombosis (DVT). Pretest probability assessment for DVT diagnosis has never been evaluated in pregnant women. Objective: To evaluate the accuracy of clinicians' subjective assessment of pretest probability for DVT diagnosis and identify prediction variables that could be used for pretest probability assessment in pregnant women with suspected DVT. Design: A cross-sectional study conducted over 7 years (March 2000 to April 2007). Setting: 5 university-affiliated, tertiary care centers in Canada. Patients: 194 unselected pregnant women with suspected first DVT. Intervention: Diagnosis of DVT was established with abnormal compression ultrasonography at presentation or on serial imaging. Pretest probability by subjective assessment was recorded by thrombosis experts for each patient before knowledge of results. Measurements: The sensitivity, specificity, negative predictive value, and likelihood ratios of subjective pretest probability assessment and their corresponding 95% CIs were calculated on the basis of the diagnosis of DVT. Patients were DVT positive if they had diagnostic compression ultrasonography at initial or serial testing or symptomatic venous thromboembolism on follow-up. Patients were DVT negative if they had negative compression ultrasonography at presentation and no venous thromboembolism on follow-up. A prediction rule for assessing DVT was derived, and an internal validation study was done to explore its performance. Results: The prevalence of DVT was 8.8%. Clinicians' subjective assessment of pretest probability categorized patients into 2 groups: low pretest probability (two thirds of patients) with a low prevalence of DVT (1.5% [95% CI, 0.4% to 5.4%]) and a negative predictive value of 98.5% (CI, 94.6% to 99.6%), and nonlow pretest probability with a higher prevalence of DVT (24.6% [CI, 15.5% to 36.7%]). Three variables (symptoms in the left leg [L], calf circumference difference ≥2 cm [E], and first trimester presentation [Ft]) were highly predictive of DVT in pregnant patients. Limitations: Few outcomes occurred. Altogether, 17 events were diagnosed during the study. The prediction rule derived should be validated on an independent sample before applying it to clinical practice. Conclusion: Subjective assessment of pretest probability seems to exclude DVT when the pretest probability is low. Moreover, 3 objective variables (“LEFt”) may improve the accuracy of the diagnosis of DVT in pregnancy. Prospective validation studies are needed. Primary Funding Source: Heart and Stroke Foundation of Ontario.