tbuckley/cabot-search huggingface dataset:
Abstract 5633: Two-compartment pharmacokinetics model of radioimmunotherapy with 131I-3F8 directly administered into the cerebrospinal fluid
Authors: Ping He, Kim Kramer, Peter Smith-Jones, Pat Zanzonico, John Humm, Steven M. Larson, Nai-Kong V. Cheung
Journal: Cancer Research (2010)

Abstract Introduction Injection of 131I-3F8 directly into the cerebrospinal fluid (CSF) through an Ommaya reservoir is a safe form of radioimmunotherapy (RIT) treatment for leptomeningeal metastasis (JCO, 25:5465, 2007). Recently, we described a one-compartment pharmacokinetics model that showed good fitting to CSF sampling data from 6 patients (JNM 50:1324, 2009). We now describe an improved two-compartment model to take into account the ventricular reservoir before 131I-3F8 distribution into the subarachnoid space and to explore limiting factors that may significantly affect the efficacy of the therapy. Methods The distribution and binding of 131I-3F8 in the cerebral spinal fluid were modeled using a system of rate equations derived from the principle of mass conservation. The model was fitted to CSF sampling data from an expanded cohort of patients (39 injections in 25 patients). Three sets of criteria were used to examine the effect of each parameter on the efficacy of the treatment. These criteria were (1) the area under the radioactivity concentration curve of the bound antibody (AUC[CIAR]) (2) the unbound antibody AUC[CIA], and (3) their therapeutic ratio (AUC[CIAR]/AUC[CIA]). In addition to parameters tested in the previous model, immunoreactivity, tumor distribution, and nonspecific binding were also tested. Results The two-compartment model showed improved fitting to patient data when compared to the one compartment model (R=0.92±0.11 versus 0.77±0.21, p=0.005). Predictions from the one compartment model were confirmed. Furthermore, we made these new observations: (1) Increasing immunoreactivity of 131I-3F8 from 10% to 90% increased both (AUC[CIAR]) and therapeutic ratio ([AUC[CIAR]/AUC[CIA]) by 7.4 fold, (2) The presence of ≤ 5% tumor cells in the ventricles or ≤ 10% of nonspecific 131I-3F8 binding to normal tissues had no appreciable effect on the therapeutic ratio. When extrapolated to a clinical setting, the model predicted that if 131I-3F8 could be split into 4 doses of 1.4 mg each and given at ≥ 24 hours apart, an antibody affinity of KD of 4 × 10−9 and immunoreactivity of 50% were adequate in order to deliver ≥10,000 Rad to tumor cells while keeping normal CSF exposure to &amp;lt;1,000 Rad. Conclusion The two compartment model of intra-ommaya radioimmunotherapy showed better fitting to patient data than the one-compartment model. This model predicted that immunoreactivity and affinity were crucial in improving therapeutic efficacy. Nevertheless, an optimal scheduling of antibody injections should permit highly favorable therapeutic ratio even with 4 nM affinities and suboptimal immunoreactivity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5633.
Diabetes and the quality and outcomes framework
Authors: Richard Greenwood, Ken Shaw, Peter Winocour
Journal: BMJ (2005)

Editor—The Association of British Clinical Diabetologists (ABCD) welcomes Kenny's editorial on the impact of the quality and outcomes framework on diabetes management and supports his plea for supporting and strengthening secondary (specialist) care diabetes services.1

The implementation of the updated contract for general medical services (GMS2) has resulted in a welcome increase in the monitoring of patients, especially those with type 2 diabetes, who have been comparatively neglected in the past. However, the need to improve glycaemic control to meet the target value of 7.5% for HbA1c has had some unforeseen consequences. In most specialist centres, referrals of patients treated with tablets for consideration of insulin treatment have increased, and many general practices do not feel confident with this. Simultaneously, it is not only extremely difficult for secondary care to attract additional resources, but there is actual “downsizing” of some specialist units by local primary care trusts, in line with the government's desire to transfer most, if not all, of chronic disease management from secondary to primary care.

This is one of the main reasons for the increasing frustration and discontent among diabetologists, which has led to a decline in recruitment into the specialty and many unfilled consultant posts. If as a result specialist services are lost then it will be difficult to re-create them. There is general agreement that integrated care is the best model for diabetes. However, integrated care will work only if there is something to integrate with. Without diabetologists and their multidisciplinary teams, general practitioners will be left unsupported and access to specialists for patients with complicated, diabetes related problems will be reduced. Most consultant diabetologists also provide an endocrine service and make a substantial contribution to acute general medicine. These functions cannot be devolved into the community.

ABCD therefore believes that the government and the Department of Health must rapidly reverse its present policy of downsizing hospital diabetes services if we are to avoid a serious deterioration in the quality of care for people with diabetes in the primary and secondary care sectors.
Hypofibrinogenemia in Chronic Myelogenous Leukemia
Authors: Fred Rosner
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Favis and his colleagues (240:1953, 1978) state that as a complication of chronic myelogenous leukemia hypofibrinogenemic bleeding "has been reported only once previously." They overlooked three other case reports.<sup>1-3</sup>One<sup>1</sup>of these three patients also had chloromas containing sea-blue histiocytes, and in the other two patients,<sup>2,3</sup>blastic transformation of their chronic myelogenous leukemia developed.
ICD Implantation and Evidence-Based Patient Selection
Authors: Steven Zweibel
Journal: JAMA (2011)

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
Comparison of Heart Vectors Calculated with Different Systems of Leads
Authors: RICHARD MCFEE
Journal: Circulation (1950)

Einthoven's equations for the heart vector are based on the assumption that voltages measured across the trunk horizontally (or vertically) are proportional to the horizontal (or vertical) component of the dipole moment of the heart's electromotive forces. One necessary consequence of this assumption is that all the horizontal (or vertical) voltages be similar, and that heart vectors calculated with different sets of these voltages and appropriate formulas be the same. An experimental test of this predicted result is described in this paper.
Mitochondrial DNA reveals cryptic oligochaete species differing in cadmium resistance
Authors: C. Sturmbauer, G. B. Opadiya, H. Niederstatter, A. Riedmann, R. Dallinger
Journal: Molecular Biology and Evolution (1999)

Species of the family Tubificidae represent a major faunal element in benthic freshwater communities throughout the world. Some of them are considered particularly tolerant of the influence of toxicants such as cadmium. One of the most abundant species, "Tubifex tubifex," is frequently used as an indicator of environmental pollution, despite considerable taxonomic problems caused by phenotypic plasticity and genetic heterogeneity. Our study provides a phylogeny of "T. tubifex" based on a segment of the mitochondrial 16S rDNA and presents a rapid PCR-based method of genotype screening which was then applied in cadmium toxicity studies on natural populations. Phylogenetic analysis identified five major mitochondrial lineages, some of them separated by large genetic distances (up to 13%) but morphologically indistinguishable, thus highly suggestive of the existence of cryptic species. All lineages were present at different frequencies in the European river populations studied, with a tendency of the more resistant lineages to occur at higher frequencies in the more tolerant populations. In fact, lineage-specific toxicity experiments showed that individuals of different mitochondrial lineages consistently varied in cadmium resistance, suggesting that in benthic oligochaetes, evolution seems to proceed predominantly through natural selection acting on physiological, rather than morphological, characters. In consequence, toxicological studies involving "T. tubifex" as a monitoring or test organism should allow for the possibility of genetic inhomogeneity of this mudworm group by combining both toxicological and genetic methods.
Opposing effects of deoxycorticosterone and spironolactone on isoprenaline-induced myocardial infarction
Authors: B. C. WEXLER
Journal: Cardiovascular Research (1979)

Adult, male, Sprague-Dawley rats were subjected to massive myocardial infarction with isoprenaline. Some of the animals were treated with the potent mineralocorticoid, deoxycorticosterone, or the anti-mineralocorticoid, spironolactone. Autopsies spaced at sequential time intervals demonstrated that circulating levels of enzymes, eg, CPK, SGOT, SGPT and LDH, lipids, eg, triglycerides, free fatty acids, and cholesterol, glucose, BUN, and corticosterone rose in conjunction with on-going necrosis and became lowered in conjunction with myocardial repair. Body and organ weights, ie, adrenal, thymus, heart, and kidney, underwent dynamic changes commensurate with necrosis and repair. Animals given isoprenaline alone died (52 % survival) during the height of their massive infarct and congestive heart failure (Days 3 and 4). Animals treated with DOC showed the most severe congestion but died (36% survival) during the late repair phase (Days 7 and 8). Animals treated with spironolactone showed the most effective clearance of thoracic fluid and also died (18% survival) during the late repair phase (Days 7 and 8). These spironolactone-treated animals had large, left ventricular aneurysms with organised, adherent thrombi. It is believed that alterations in electrolyte balance induced by DOC or spironolactone caused changes in adrenocortical function which greatly modified the usual pathophysiological response to myocardial infarction.
Tapeworms and Seizures — Treatment and Prevention
Authors: James H. Maguire
Journal: New England Journal of Medicine (2004)

It may come as a surprise that a lowly tapeworm is responsible for as many as 10 percent of cases in which a patient presents with seizures to an emergency room in a large urban hospital in New Mexico or California. In fact, cysticercosis, infection with the larval stage of the pork tapeworm, Taenia solium, is the most common parasitic disease of the central nervous system worldwide, and it is the leading cause of late-onset epilepsy in many developing countries. Most of the estimated 50 million cases of cysticercosis originate in poor communities of Latin America, Asia, and Africa, but . . .
Using Satellite-Based Spatiotemporal Resolved Air Temperature Exposure to Study the Association between Ambient Air Temperature and Birth Outcomes in Massachusetts
Authors: Itai Kloog, Steven J. Melly, Brent A. Coull, Francesco Nordio, Joel D. Schwartz
Journal: Environmental Health Perspectives (2015)

Studies looking at air temperature (Ta) and birth outcomes are rare.We investigated the association between birth outcomes and daily Ta during various prenatal exposure periods in Massachusetts (USA) using both traditional Ta stations and modeled addresses.We evaluated birth outcomes and average daily Ta during various prenatal exposure periods in Massachusetts (USA) using both traditional Ta stations and modeled address Ta. We used linear and logistic mixed models and accelerated failure time models to estimate associations between Ta and the following outcomes among live births > 22 weeks: term birth weight (≥ 37 weeks), low birth weight (LBW; < 2,500 g at term), gestational age, and preterm delivery (PT; < 37 weeks). Models were adjusted for individual-level socioeconomic status, traffic density, particulate matter ≤ 2.5 μm (PM2.5), random intercept for census tract, and mother's health.Predicted Ta during multiple time windows before birth was negatively associated with birth weight: Average birth weight was 16.7 g lower (95% CI: -29.7, -3.7) in association with an interquartile range increase (8.4 °C) in Ta during the last trimester. Ta over the entire pregnancy was positively associated with PT [odds ratio (OR) = 1.02; 95% CI: 1.00, 1.05] and LBW (OR = 1.04; 95% CI: 0.96, 1.13).Ta during pregnancy was associated with lower birth weight and shorter gestational age in our study population.
Vaginal Bleeding from Potassium Permanganate as an Abortifacient
Authors: James F. McDonough
Journal: New England Journal of Medicine (1945)

BURNS of the vagina and cervix due to the use of potassium permanganate tablets as an abortifacient constitute a new and gradually increasing serious complication of early pregnancy in and around Boston. Since March, 1936, when this diagnosis was first made at the Boston City Hospital, 65 cases have been treated by the Gynecological Service. Inasmuch as this entity has been so infrequently mentioned in the literature, it is the purpose of this paper to present its important features and the report of a case with serious sequelae.A review of the literature reveals that there has been only one . . .
A Diagnostic Strategy to Distinguish Autoimmune Pancreatitis From Pancreatic Cancer
Authors: Suresh T. Chari, Naoki Takahashi, Michael J. Levy, Thomas C. Smyrk, Jonathan E. Clain, Randall K. Pearson, Bret T. Petersen, Mark A. Topazian, Santhi S. Vege
Journal: Clinical Gastroenterology and Hepatology (2009)
Neuronal Activity and CaMKII Regulate Kinesin-Mediated Transport of Synaptic AMPARs
Authors: Frédéric J. Hoerndli, Rui Wang, Jerry E. Mellem, Angy Kallarackal, Penelope J. Brockie, Colin Thacker, David M. Madsen, Andres V. Maricq
Journal: Neuron (2015)
Mitochondrial gene expression is impaired by ethanol exposure in cultured chick cardiac myocytes
Authors: J Kennedy
Journal: Cardiovascular Research (1998)

Objective: A depression in cytochrome c oxidase (COX) activity occurs following chronic embryonic ethanol exposure in vivo. The aim of this study was to examine the effect of chronic ethanol exposure on COX activity in isolated cardiac cells maintained in vitro. Additionally, the mechanism by which ethanol produces an impairment in COX activity was evaluated by examining mitochondrial gene expression. Methods: Spontaneously beating cardiac myocyte cultures were established from 10-day embryonic chick hearts. Various concentrations of ethanol (0–250 mM) were introduced at the time of plating and cells were harvested over 7 days. COX activity was determined in myocyte homogenates. The levels of nuclear-encoded (COXIV) and mitochondrial-encoded (COXII) subunit proteins were measured by Western blotting. Relative levels of mitochondrial DNA and the mitochondrially-encoded COXIII mRNA were determined by Southern and Northern blotting. Results: A consistent decrease in COX activity in ethanol-exposed cardiac myocytes of approximately 30% was observed with an ethanol concentration of 25 mM. Increasing the ethanol concentration to 250 mM produced only a minor enhancement of this effect, while severely decreasing cellular viability. The content of the mitochondrially-encoded COXII subunit was reduced by ethanol exposure, while that of the nuclear-encoded COXIV subunit was unchanged. The content of the mitochondrially-encoded COXIII mRNA was unchanged by ethanol exposure. However, prolonged ethanol exposure produced an increase in mitochondrial DNA levels in cardiac myocytes. Conclusions: Ethanol exposure of cardiac myocytes produces deficits in COX activity in the absence of systemic variables, indicating that ethanol has a direct effect on cardiac mitochondria. The ethanol-induced decrease in COX activity is correlated with a specific decrease in at least one mitochondrially-encoded gene product, COXII. No changes were observed in the level of the nuclear-encoded COXIV subunit, indicating that expression of this nuclear-encoded gene is not impaired by ethanol exposure.
Toxoplasmosis, Lymphoma, or Both?
Authors: FLORA M. BARLOTTA
Journal: Annals of Internal Medicine (1969)

Five patients with toxoplasmosis,three with Hodgkin's disease and toxoplasmosis, and two with other lymphomatous disorders and positive toxoplasma titers were studied. Both toxoplasmosis and lymphoma may be characterized by fever, weight loss, lymphadenopathy, hepatosplenomegaly, rash, neurologic abnormalities, anemia, and increased concentration of the serum gamma globulins. Further, the cellular pleomorphism of the lymph node infected with Toxoplasma gondii may make it difficult to distinguish between lymphoma and toxoplasmosis. Since the treatment for these two disorders is different, it is essential to recognize that they can mimic each other.
Abstract LB-328: Highly sensitive detection of miRNA and mRNA from frozen, FFPE tissue and body fluid samples by expression microarray
Authors: Satoko Takizawa, Hiroko Sudo, Yoji Ueda, Toshihiko Kuroda, Makiko Ichikawa, Osamu Nomura, Hideo Akiyama
Journal: Cancer Research (2011)

Abstract The RNA profiling from clinical samples readily obtainable in the routine care, such as blood or FFPE samples, is a promising method to find the unknown high-value diagnostic markers. However, as RNA is subjected to degradation even in properly-collected, and immediately frozen tissue, it is more difficult to obtain intact RNA from FFPE or body fluid samples for diagnostic analysis. “3D-Gene” is a highly sensitive gene expression microarray, featuring the unique pillar structure on the substrate and the beads agitation system during the hybridization reaction. Using “3D-Gene”, we achieved highly sensitive detection of mRNA or miRNA from diagnostically important clinical samples. Total RNA was extracted from human serum, plasma and frozen or FFPE tissue samples, with the recommended protocol for each sample. For mRNA detection, total RNA was reverse-transcribed to cDNA and labeled with fluorescent dye directly or after the amplification. For miRNA detection, total RNA was labeled with fluorescent dye directly. These pretreated target nucleotides were hybridized to “3D-Gene” while the hybridized buffer containing target nucleotides was agitated by beads during hybridization. The hybridized microarrays were washed and scanned for image acquisition. (1) With “3D-Gene”, we could detect the mRNA expression profile from FFPE samples with high reproducibility. We also showed high correlation of the expression profiles between FFPE and frozen tissue samples. With 500 ng total RNA obtained from frozen as well as FFPE tissue samples, miRNA was reproducibly detected at attomolar level. Some miRNA biomarkers for various cancers were found from FFPE samples. (2) Serum and plasma are suggested to contain microsomes in which miRNA is enclosed. miRNA from serum and plasma samples were detected with high sensitivity and reproducibility with “3D-Gene”. Some miRNA biomarkers for various cancers were found from patients' serum. “3D-Gene” is a potential tool for detecting transcriptome with high sensitivity and useful for quest and validation of diagnostic biomarkers from clinical samples. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-328. doi:10.1158/1538-7445.AM2011-LB-328
Selection of Unadapted, Pathogenic SHIVs Encoding Newly Transmitted HIV-1 Envelope Proteins
Authors: Gregory Q. Del Prete, Braiden Eilers, Brian Moldt, Brandon F. Keele, Jacob D. Estes, Anthony Rodriguez, Marissa Sampias, Kelli Oswald, Randy Fast, Charles M. Trubey, Elena Chertova, Jeremy Smedley, Celia C. LaBranche, David C. Montefiori, Dennis R. Burton, George M. Shaw, Marty Markowitz, Michael Piatak, Vineet N. KewalRamani, Paul D. Bieniasz, Jeffrey D. Lifson, Theodora Hatziioannou
Journal: Cell Host & Microbe (2014)
Erythropoietin for End-Stage Renal Disease
Authors: John W. Adamson, Joseph W. Eschbach
Journal: New England Journal of Medicine (1998)

Currently, there are approximately 200,000 patients with end-stage renal disease in the United States who require dialysis therapy to stay alive, and dialysis is initiated in nearly 70,000 new patients each year.1 About 90 percent of patients undergoing dialysis have anemia as a result of erythropoietin deficiency. Anemia contributes substantially to morbidity and mortality among these patients, and the introduction of recombinant human erythropoietin (epoetin) therapy in 1989 significantly improved the quality of life, reduced the need for red-cell transfusions,2 and improved measures of various physiologic functions such as maximal exercise capacity and cognition. Although epoetin is expensive, costing the . . .
Skin Cancer Target
Authors: Tracy Hampton
Journal: JAMA (2011)

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