tbuckley/cabot-search huggingface dataset:
Mild Hyperthermia Enhances Transport of Liposomal Gemcitabine and Improves In Vivo Therapeutic Response
Authors: Dickson K. Kirui, Christian Celia, Roberto Molinaro, Shyam S. Bansal, Donato Cosco, Massimo Fresta, Haifa Shen, Mauro Ferrari
Journal: Advanced Healthcare Materials (2015)

Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod‐mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery, and antitumor efficacy in pancreatic cancer CAPAN‐1 tumor model. MHT treatment leads to a threefold increase in accumulation of 80‐nm liposomes and enhances spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment lead to a threefold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg kg −1 Gem Lip leads to a twofold increase in therapeutic efficacy and inhibition of CAPAN‐1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect is confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg kg −1 Gem Lip achieves similar therapeutic efficacy as the use of 60 mg kg −1 free gemcitabine. In conclusion, improvements in vivo efficacy are demonstrated resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.
The Typical Appearance of Focal Nodular Hyperplasia in Triple-Phase CT Scan, Hepatobiliary Scan, and Tc-99m Sulfur Colloid Scan With SPECT
Authors: Lien T. Huynh, Sun Y. Kim, Thomas F. Murphy
Journal: Clinical Nuclear Medicine (2005)

A healthy, asymptomatic 37-year-old woman was found to have elevated liver enzymes on routine examination. All other laboratory tests were within normal limits with the exception of elevated ferritin and total iron-binding capacity. The patient denied the use of oral contraceptives. Subsequent studies with ultrasound and CT scan revealed hepatic masses in both lobes. The patient was referred for possible resection or ablation of masses. Further studies with triple-phase CT scan of the liver, hepatobiliary scan, and Tc-99m sulfur colloid scan with SPECT revealed the typical appearance of focal nodular hyperplasia (FNH).
Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children
Authors: Marc-André Verner, Jaime E. Hart, Sharon K. Sagiv, David C. Bellinger, Larisa M. Altshul, Susan A. Korrick
Journal: Environmental Health Perspectives (2015)

BackgroundEpidemiologic studies of postnatal PCB exposure and behavior have not reported consistent evidence of adverse associations, possibly because of challenges in exposure estimation. We previously developed a pharmacokinetic model to improve estimation of children's PCB exposure.ObjectivesWe aimed to assess whether estimated serum PCB levels in infancy are associated with attention deficit/hyperactivity disorder (ADHD)–related behaviors at 8 years of age among children whose cord serum PCB levels were previously shown to be associated with ADHD-related behaviors.MethodsWe used a pharmacokinetic model to estimate monthly serum polychlorinated biphenyl (PCB)–153 levels in 441 infants (ages 1–12 months) based on parameters such as breastfeeding and cord serum PCB-153 levels. Behavior was evaluated at age 8 using the Conners' Rating Scale for Teachers (CRS-T). Associations between PCB-153 levels and ADHD-related CRS-T indices were assessed using multivariable quantile regression at the 50th and 75th percentiles of CRS-T scores, where higher percentiles reflect more adverse behaviors.ResultsCord serum PCB-153 levels (median, 38 ng/g lipids) were associated with ADHD-related behaviors, although statistical significance was observed with quantile regression models only at the 75th percentile. Associations with postnatal exposure estimates were attenuated. For example, hyperactive-impulsive behavior scores at age 8 years were 0.9 points (95% CI: 0.2, 2.5), 0.5 points (95% CI: 0.3, 2.3), and 0.3 points (95% CI: –0.2, 1.5) higher in association with interquartile range increases in serum PCB-153 at birth, 2 months, and 12 months of age, respectively.ConclusionsAssociations between estimated postnatal PCB-153 exposures and ADHD-related behaviors at 8 years of age were weaker than associations with PCB-153 concentrations measured in cord serum at birth.CitationVerner MA, Hart JE, Sagiv SK, Bellinger DC, Altshul LM, Korrick SA. 2015. Measured prenatal and estimated postnatal levels of polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old children. Environ Health Perspect 123:888–894; http://dx.doi.org/10.1289/ehp.1408084
Efficacy of Reslizumab in Patients with Poorly Controlled Eosinophilic Asthma: Subgroup Analysis of Patients with Nasal Polyps
Authors: S. Mathur, M. Castro, F. Hargreave, F. Xie, H.J. Wilkins, T. Henkel, P. Nair
Journal: Journal of Allergy and Clinical Immunology (2011)
Association Between Myocardial Infarction and the Mast Cells in the Adventitia of the Infarct-Related Coronary Artery
Authors: Petri Laine, Maija Kaartinen, Antti Penttilä, Pertti Panula, Timo Paavonen, Petri T. Kovanen
Journal: Circulation (1999)

Background —Histamine, a product of mast cells, is an effective vasoconstrictor of atherosclerotic coronary arteries. Because it has been suggested that coronary spasm plays a role in acute coronary syndromes such as myocardial infarction (MI), we quantified and characterized the mast cells in the adventitia of infarct-related coronary arteries. Methods and Results —In a series of 17 autopsied MI patients, we identified the segment of the left coronary artery with ruptured plaque responsible for the infarction. More distal segments from the infarct-related coronary artery, either with nonruptured plaques or with normal intima, were also studied. Corresponding segments taken from left coronary arteries obtained from 17 patients who had died of noncardiac causes served as controls. Adventitial mast cells in the infarct-related and the control coronary arteries were identified immunohistochemically by staining for tryptase. In the infarct-related coronary arteries, we also stained for chymase and histamine. Moreover, T lymphocytes and macrophages were identified immunohistochemically and counted. In the infarct-related coronary arteries, significantly larger numbers of mast cells were present in the adventitia backing ruptured plaques (98±40 mast cells/mm 2 , mean±SD) than in the adventitia backing nonruptured plaques (41±12 mast cells/mm 2 ; P &lt;0.001) or backing normal intima (19±8 mast cells/mm 2 ; P &lt;0.001). No such difference was found among the 3 different segments in the control coronary arteries. The majority of mast cells contained not only tryptase but also chymase. Mast cells were the only cells in the coronary adventitia that contained histamine. The proportion of adventitial mast cells that were degranulated was highest in the segments with ruptured plaques. The numbers of adventitial macrophages and T lymphocytes were also increased in the segments with plaque rupture. Conclusions —In infarct-related coronary arteries, the number of degranulated mast cells in the adventitia backing ruptured plaques is increased. Histamine released from the degranulated mast cells may reach the media, where it may locally provoke coronary spasm and thus contribute to the onset of MI.
Correlation of IgM anti-hepatitis D virus (HDV) to HDV RNA in sera of chronic HDV
Authors: Sugantha Govindarajan, Sanjeev Gupta, Boontar Valinluck, Allan G. Redeker
Journal: Hepatology (1989)

One hundred forty-four serum samples from 52 patients with chronic hepatitis D virus infection were analyzed for hepatitis D virus RNA by dot-blot hybridization using hepatitis D virus cDNA probe labeled with 32P. The results were correlated with the presence of serum IgM anti-hepatitis D virus and hepatitis D antigen in liver biopsy specimens when available. Although there was a trend of positive correlation between serum hepatitis D virus RNA and IgM anti-hepatitis D virus, no statistical significance could be found. In the serum samples with hepatitis D virus RNA, 32% were found to be negative for IgM anti-hepatitis D virus. Therefore, in chronic hepatitis D virus, absence of IgM anti-hepatitis D virus does not rule out active viral infection, as suggested by previous studies. There was a strong correlation between serum hepatitis D virus RNA and hepatic hepatitis D virus antigen. These data indicate that detection of hepatitis D virus RNA in serum samples is a reliable noninvasive marker of active viral infection.
Doing Right: Everyday Medical Ethics
Authors: Nicholas E. Davies
Journal: JAMA (1984)

New books on medical ethics abound. This small volume is the author's personal code of medical ethics, which he has developed during his years as a clinician and teacher.  His central theme is his concern for the patient; the patient's primacy is found throughout. He uses this theme in briefly discussing such topics as the responsibilities of the physician to the patient, to his or her own family, and to society; treatment; the undesirable patient; and relationships with students, residents, fellows, and faculty. He speaks of the dehumanization process in medicine, self-righteousness and demeanor, self-discipline and personal intrusion, all as they relate to the patient.  A second major theme found throughout this book deals with ethics and medical education, a theme called  scholarship. The author believes that medical ethics is best taught  a faculty who are humane scholars and reinforced by house staff whose ethical concerns are clearly
Metabolism of trichloroethylene.
Authors: L H Lash, J W Fisher, J C Lipscomb, J C Parker
Journal: Environmental Health Perspectives (2000)

A major focus in the study of metabolism and disposition of trichloroethylene (TCE) is to identify metabolites that can be used reliably to assess flux through the various pathways of TCE metabolism and to identify those metabolites that are causally associated with toxic responses. Another important issue involves delineation of sex- and species-dependent differences in biotransformation pathways. Defining these differences can play an important role in the utility of laboratory animal data for understanding the pharmacokinetics and pharmacodynamics of TCE in humans. Sex-, species-, and strain-dependent differences in absorption and distribution of TCE may play some role in explaining differences in metabolism and susceptibility to toxicity from TCE exposure. The majority of differences in susceptibility, however, are likely due to sex-, species-, and strain-dependent differences in activities of the various enzymes that can metabolize TCE and its subsequent metabolites. An additional factor that plays a role in human health risk assessment for TCE is the high degree of variability in the activity of certain enzymes. TCE undergoes metabolism by two major pathways, cytochrome P450 (P450)-dependent oxidation and conjugation with glutathione (GSH). Key P450-derived metabolites of TCE that have been associated with specific target organs, such as the liver and lungs, include chloral hydrate, trichloroacetate, and dichloroacetate. Metabolites derived from the GSH conjugate of TCE, in contrast, have been associated with the kidney as a target organ. Specifically, metabolism of the cysteine conjugate of TCE by the cysteine conjugate ss-lyase generates a reactive metabolite that is nephrotoxic and may be nephrocarcinogenic. Although the P450 pathway is a higher activity and higher affinity pathway than the GSH conjugation pathway, one should not automatically conclude that the latter pathway is only important at very high doses. A synthesis of this information is then presented to assess how experimental data, from either animals or from (italic)in vitro (/italic)studies, can be extrapolated to humans for risk assessment. (italic)Key words(/italic): conjugate beta-lyase, cysteine glutathione, cytochrome P450, glutathione (italic)S(/italic)-transferases, metabolism, sex dependence, species dependence, tissue dependence, trichloroethylene.
Case 4-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, A.P. Monaco, N.L. Harris
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 36-year-old man was admitted to the hospital because of pain in the left leg.The patient had had diabetes mellitus since the age of nine years. Six years before admission the nephrotic syndrome and hypertension developed. One year later he received laser treatment to the right eye because of diabetic retinopathy. Four years before entry chronic renal failure occurred and progressed, and six months later extracorporeal hemodialysis was begun. Four months later bilateral native nephrectomy was performed, and a cadaveric renal allograft was implanted. Antithymocyte globulin, prednisone, and azathioprine were administered. The patient was discharged on . . .
A Clinical Lecture UPON THE SURGICAL ASPECTS OF HAEMOPHILIA, WITH ESPECIAL REFERENCE TO TWO CASES OF VOLKMANN'S CONTRACTURE RESULTING FROM THIS DISEASE
Authors: E. W. H. Groves
Journal: BMJ (1907)

TM B -6i r lest, as in this case, the outcome proves the cause to have been, though not organic disease of the valves or vessels, something more definite and dangerous than a mere nerve-storm.In the treatment of aortic disease the primary object to achieve is the establishment and maintenance of sufficie'nt compensation.In the case of our first patient, who suffered recently from rheumatic fever, the chances are that his compensation never became firmly established -that is to Lay, that the length of time over which he rested and the amount of care which wa's taken of him
Doxorubicin pharmacokinetics following two different liposomal formulations (CAELYX™ vs MYOCET™) in advanced breast cancer patients.
Authors: J Schueller, M Czejka, E Krexner, K Aigner, B Gruenberger
Journal: Cancer Research (2009)

Abstract Abstract #2128 Background: Liposomal encapsulation of Doxorubicin (DOX) was designed to minimize healthy tissue distribution by altering pharmacokinetics (PK) thus reducing cardiotoxicity while preserving antitumour efficacy. Study objective was to compare the PK behaviour of the two main liposomal formulations of DOX, i.e. pegylated (Caelyx, C) versus non pegylated (Myocet, M), in a single center study including 17 MBC patients, all Anthracyclin pretreated with additional risk faktors.&amp;#x2028; Methods: Cohort 1 consisted of 10pts (mean age 62, 49-77) treated by C as 1HR infusion of 50mg/m²/4 wks. Plasma samples were collected at timepoints min 0, 30, 60, 120, 180 and d1, 7, 14, 28. In cohort 2, 7 pts (mean age 58, 51 – 70) received M 75mg/m² 1H Infusion / 3wks, plasma levels determined at min 0, 30, 60, 90, 120, 180 and d1, 2, 3. Total amount of DOX was determined following the 1st infusion respectively, analytic procedure included solid phase extraction quantification by HPLC and PK analysis by Win Nonlin Pro. Doxorubicinol was detected after M only.&amp;#x2028; Results: in Cohort1 after C, mean Cmax of 6.8 µg/ml surprisingly occured at a mean tmax of 2.3 d, log conc time curve showed linear decrease of DOX conc suggesting continuous release into the tissue (mean conc d 7 3.3, d 14 1.0, d 21 0.3, d 28 0.09 µg/ml) . No metabolites were found, AUC (does not represent reliable drug exposure and bioavailability of DOX) expressed as µg/ml.d was 54.6. In contrast AUClast of M was calculated as 35µg ml.H and mean Cmax by 7.5 µg/ml at infusion end. DOXol was measured in all M treated patients at a slower metabolisation rate and late appearance compared to conventional DOX. t/2 el of C was 6 times longer than that of M (HR 90 vs 15). Differences in plasma disposition and PK of M vs C are depicted in table 1 and compared to pooled data of conventional DOX derived from former studies (50 mg/m² 30min inf, n=40). Cltot of conv. DOX was 10 fold higher than M and 500 fold higher than C, Vss about 12 times that of M and 70 times that of C. These PK differences underlines a different toxicity profile between PEGL (C, PPE syndrome) and NPEGL (M, myelotox, nausea), both reducing cardiac tox by avoiding peak plasma levels due to prolonged circulation time.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2128.
Pemberton's Sign
Authors: Shehzad Basaria, Roberto Salvatori
Journal: New England Journal of Medicine (2004)

A 58-year-old woman with a 20-year history of goiter presented with a two-month history of progressive dyspnea on exertion, occasional stridor, and a choking sensation while supine. She had previously been asymptomatic. Physical examination revealed a diffusely enlarged thyroid with no palpable nodules (Panel A), but the lower poles of the thyroid were not palpable. Within 30 seconds after she raised both arms simultaneously (Pemberton's maneuver), marked facial plethora (Pemberton's sign) developed, indicating compression of the jugular veins (Panel B). The patient's serum thyrotropin and free thyroxine concentrations were normal. Computed tomography of the neck revealed a large goiter extending . . .
Prevalence of Colorectal Neoplasm Among Patients With Newly Diagnosed Coronary Artery Disease
Authors: Annie On On Chan, Man Hong Jim, Kwok Fai Lam, Jeffrey S. Morris, David Chun Wah Siu, Teresa Tong, Fook Hong Ng, Siu Yin Wong, Wai Mo Hui, Chi Kuen Chan, Kam Chuen Lai, Ting Kin Cheung, Pierre Chan, Grace Wong, Man Fung Yuen, Yuk Kong Lau, Stephen Lee, Ming Leung Szeto, Benjamin C. Y. Wong, Shiu Kum Lam
Journal: JAMA (2007)

Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated.To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases.Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years.The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex.The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by chi2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD.In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.
Sleeping Sickness Marker
Authors: Tracy Hampton
Journal: JAMA (2008)

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Identification of unique peanut and soy allergens in sera adsorbed with cross-reacting antibodies
Authors: Philippe A. Eigenmann, A.Wesley Burks, Gary A. Bannon, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (1996)

Soybean and peanut are members of the legume family and share several common antigenic fractions. Patients allergic to one of these foods have serum IgE antibodies that immunologically cross-react with other legumes. Nevertheless, ingestion of other legumes generally does not induce an allergic reaction, suggesting that cross-reacting antibodies are not clinically relevant.This study was designed to identify unique peanut or soybean antigenic fractions, with sera adsorbed to remove cross-reacting antibodies, thus resulting in sera with IgE antibodies unique to either soy or peanut.Cross-reacting antibodies to soy were removed from the sera of two patients allergic to peanut and soy and three patients allergic to peanut by soy-affinity chromatography. Cross-reacting antibodies to peanut were adsorbed from the sera of a patient allergic to peanut and soy and a patient allergic to peanut by peanut-affinity chromatography. Adequate removal of cross-reacting antibodies was verified by ELISA after each adsorption step. Unadsorbed sera and sera adsorbed to remove cross-reacting antibodies (either to soy or to peanut) were assayed for specific IgE binding to peanut or soy immunoblots.Unique peanut-specific IgE antibodies (i.e., soy antibody-adsorbed) were found to bind to peanut fractions at 46, 29, 25, 19, 17, 14, and 5 kd on immunoblots of whole peanut protein. Similarly, unique soy-specific IgE (i.e., peanut antibody-adsorbed) were found to bind a fraction at 46 kd, and to a lesser extent, to a fraction at 21 kd on immunoblots of whole soy protein. The 73% reduction of IgE antibody binding to peanut by ELISA after adsorption of cross-reacting antibodies indicates extensive cross-reactivity between soy and peanut antigens.Antigen-affinity chromatography is an effective method for removal of cross-reacting antibodies. We identified IgE antibody binding (with sera where cross-reacting antibodies were removed) to several unique antigenic fractions of peanut and soy. Further studies will determine the clinical significance of these fractions in IgE-mediated food hypersensitivity reactions.