tbuckley/cabot-search huggingface dataset:
Stable and Efficient Paclitaxel Nanoparticles for Targeted Glioblastoma Therapy
Authors: Qingxin Mu, Mike Jeon, Meng‐Hsuan Hsiao, Victoria K. Patton, Kui Wang, Oliver W. Press, Miqin Zhang
Journal: Advanced Healthcare Materials (2015)

Development of efficient nanoparticles (NPs) for cancer therapy remains a challenge. NPs are required to have high stability, uniform size, sufficient drug loading, targeting capability, and ability to overcome drug resistance. In this study, the development of a NP formulation that can meet all these challenging requirements for targeted glioblastoma multiform (GBM) therapy is reported. This multifunctional NP is composed of a polyethylene glycol‐coated magnetic iron oxide NP conjugated with cyclodextrin and chlorotoxin (CTX) and loaded with fluorescein and paclitaxel (PTX) (IONP‐PTX‐CTX‐FL). The physicochemical properties of the IONP‐PTX‐CTX‐FL are characterized by transmission electron microscope, dynamic light scattering, and high‐performance liquid chromatography. The cellular uptake of NPs is studied using flow cytometry and confocal microscopy. Cell viability and apoptosis are assessed with the Alamar Blue viability assay and flow cytometry, respectively. The IONP‐PTX‐CTX‐FL had a uniform size of ≈44 nm and high stability in cell culture medium. Importantly, the presence of CTX on NPs enhanced the uptake of the NPs by GBM cells and improved the efficacy of PTX in killing both GBM and GBM drug‐resistant cells. The IONP‐PTX‐CTX‐FL demonstrated its great potential for brain cancer therapy and may also be used to deliver PTX to treat other cancers.
833 LIVER FIBROSIS ASSESSMENT IN CHRONIC HEPATITIS C: EVOLUTION OF CLINICAL PRACTICE IN A LARGE COHORT OF 4546 PATIENTS BETWEEN 2003 AND 2006
Authors: F. Roudot-Thoraval, D. Ouzan, J. Denis, D. Guyader, M. Doffoel, P. Delasalle, A. Abergel, P. Marcellin, M. Chousterman, C. Hayem, I. Lonjon-Domanec, M. Bourliere
Journal: Journal of Hepatology (2008)
Heparin‐induced thrombocytopenia: Current status and diagnostic challenges
Authors: Stavroula A Otis, James L. Zehnder
Journal: American Journal of Hematology (2010)

Heparin-induced thrombocytopenia (HIT) is a fairly common and potentially catastrophic complication of heparin therapy. Diagnosing HIT remains a challenge, as the patients at risk often have other reasons for thrombocytopenia and/or thrombosis. HIT is considered a clinicopathologic disorder whose diagnosis is generally made on the basis of both clinical criteria and the presence of "HIT antibodies" in the patient's serum or plasma. There are two basic laboratory approaches to detect HIT antibodies. The immunoassays detect antibodies based on their binding properties, whereas the functional assays detect antibodies based on their platelet-activating properties. Prompt and accurate diagnosis of HIT is imperative, as overdiagnosis exposes patients to alternative anticoagulants and their associated bleeding risks, whereas under- or delayed diagnosis leaves patients vulnerable to the thromboembolic sequelae of HIT, which can be life threatening. A critical interpretation of laboratory results by the clinician is an essential component of diagnosing HIT. This requires a keen understanding of the current concepts in the pathophysiologic mechanisms of the disease, and the application of these concepts when interpreting the results of both the functional and immunoassays. Equally important is an awareness of the strengths and weaknesses, as well as the current lack of standardization and proficiency testing, of these assays.
Post-partum Mental Disorders in an Unselected Sample: Frequency of Symptoms and Predisposing Factors
Authors: L. Jacobson, L. Kaij, A. Nilsson
Journal: BMJ (1965)

The aim of the present study was to explore the relation between childbirth and mental disorder. Particular attention was paid to the frequency of pre-pregnancy and post-partum psychiatric symptoms, and possible prognostic and predisposing factors, as aids in predicting the course of such symptoms. From clinical experience we know that psychoses and neuroses may begin during pregnancy, delivery, and the puer perium. Earlier studies of mental illness following parturition were mainly concerned with psychoses?that is, con fusional states, schizophrenia, and massive affective disorders. So far there have been few investigations into mild mental ill ness?that is, neuroses, asth?nie reactions, and mild affective disorders (Hamilton, 1962 ; Jansson, 1963). Most of those studies have been carried out on patients treated in a mental hospital after delivery, which implies a bias or at least a selection of the most serious cases.
AN IMPROVED NIPPLE-SHIELD.
Authors: J. MORRIS SLEMONS
Journal: JAMA (1906)

The ordinary type of nipple-shield is so frequently unsatisfactory in cases where such an appliance is urgently needed that I have designed a new model to overcome some very obvious defects in the old one. It very often happens that the shield now on the market can not be used at all, and, indeed, in most instances where it is used there is considerable discomfort occasioned either the mother or the child. The mother must invariably assume an awkward position in order that the milk may flow in the proper direction. If in bed she must turn so that she lies practically over the child; if sitting up she must bend forward at a very uncomfortable angle, otherwise the milk will remain in the shield. The child not infrequently is restless and dissatisfied because it is compelled to nurse so long before any milk reaches it. This is due to
An Epidemic of Mysterious Cardiopulmonary Arrests
Authors: Jeoffrey K. Stross, D. Michael Shasby, William R. Harlan
Journal: New England Journal of Medicine (1976)

Over a six-week period, a striking increase in the incidence of cardiopulmonary arrests occurred at the Ann Arbor Veterans Administration Hospital, Criminal administration of a muscle-paralyzing agent was implicated. An epidemiologic investigation les to a description of the classic features of an epidemic; time, place, person, agent and mode of transmission. Control of the agent and susceptible patients led to cessation of the epidemic. Although the perpetrator was not specifically identified, the concurrent criminal investigation was aided by the data developed in the medical investigation. On the basis of this experience, we propose a surveilliance mechanism for early detection of increased critical incidents, such as cardiopulmonary arrests, and a scheme for systematically examining similar events.
Cancer of the Head and Neck
Authors: Philip Rubin
Journal: JAMA (1972)

The incipient signs of tumors of the nose and paranasal sinus often masquerade as chronic inflammatory conditions, nasal discharges, nosebleeds, obstruction to breathing, and sinusitis. Over a period of months, these presenting symptoms delude both the patient and physician as to the seriousness of the underlying condition. The high prevalence of chronic sinusitis and the extremely low incidence of malignant tumors of the nasal cavity and paranasal sinuses (0.2% of all cancers and 3.0% of upper respiratory and alimentary tract cancers)<sup>1</sup>further lull the clinician into a false sense of security as he notes temporary response to decongestants and antibiotics. The development of a persistent, dull, aching pain in the teeth, the eyes, or deep in the nose or sinus is evidence of bone invasion and destruction, and moderate advancement of the disease. Patches of membranes and hypesthesia about the skin of the lower eyelid, anterior face, upper lip,
Referrals and outcomes for fertility preservation in a cohort of breast cancer patients
Authors: N. Sarwar, A. Carby, C. R. Coombes, S. Lavery, G. Trew, C. Palmieri
Journal: Journal of Clinical Oncology (2008)

20695 Background: The diagnosis of breast cancer in younger women and the need for systemic treatment has potential physical, psychological and social implications. The impact on fertility being one of these, this can have a profound effect on emotional well being and self-esteem. Given this problem appropriate referral and management within specialised fertility units with expertise in managing onco-fertility issues is necessary. Methods: Case notes of breast cancer patients referred to the Wolfson Family Clinic at Imperial Healthcare NHS trust, UK were reviewed. Results: 22 women were identified with a median age of 36 (range = 27–49). 21 women underwent ovarian stimulation. During ovarian stimulation the median day 2 FSH was 6.5 IU/L (range 2.5–11.58) with a median peak estradiol of 2066 pmol/L (range 240–10,057). The median number of collected oycytes was 5 (Range = 2–22). In 16 women oocytes were fertilised and embryos frozen, while 5 had oocytes frozen. 14 women had fertilisation done via intra-cytoplasmic sperm injection (ICSI) and 2 via in-vitro fertilisation (IVF). Where ICSI was utilised a median of 4 oocytes were injected (2–11), resulting in a median of 3 fertilised oocytes and embryos being frozen (range = 0–8). In IVF cases 9 and 12 oocytes were produced with 7 and 11 being fertilised respectively, all led to embryos which were frozen. In those women who underwent oocyte freezing alone a median of 15 oocytes (range 2–22) were collected and frozen. To date there have been 2 live births from 3 frozen embryo replacements. Method of ovarian stimulation, data on time to definitive systemic therapy from referral to fertility unit and outcome data will be presented. Conclusions: Fertility preservation is viable and successful prior to cytotoxic therapy for breast cancer and can lead to successful pregnancies. Work is required to investigate any potential detrimental effect on long term outcome. No significant financial relationships to disclose.
Inhibition of Tumor Angiogenesis and Growth by a Small-Molecule Multi-FGF Receptor Blocker with Allosteric Properties
Authors: Françoise Bono, Frederik De Smet, Corentin Herbert, Katrien De Bock, Maria Georgiadou, Pierre Fons, Marc Tjwa, Chantal Alcouffe, Annelii Ny, Marc Bianciotto, Bart Jonckx, Masahiro Murakami, Anthony A. Lanahan, Christof Michielsen, David Sibrac, Frédérique Dol-Gleizes, Massimiliano Mazzone, Serena Zacchigna, Jean-Pascal Herault, Christian Fischer, Patrice Rigon, Carmen Ruiz de Almodovar, Filip Claes, Isabelle Blanc, Koen Poesen, Jie Zhang, Inmaculada Segura, Geneviève Gueguen, Marie-Françoise Bordes, Diether Lambrechts, Roselyne Broussy, Marlies van de Wouwer, Corinne Michaux, Toru Shimada, Isabelle Jean, Silvia Blacher, Agnès Noel, Patrick Motte, Eran Rom, Jean-Marie Rakic, Susumu Katsuma, Paul Schaeffer, Avner Yayon, Ann Van Schepdael, Harald Schwalbe, Francesco Luigi Gervasio, Geert Carmeliet, Jef Rozensky, Mieke Dewerchin, Michael Simons, Arthur Christopoulos, Jean-Marc Herbert, Peter Carmeliet
Journal: Cancer Cell (2013)
A 93-Year-Old Man With Advanced Dementia and Eating Problems
Authors: Susan L Mitchell
Journal: JAMA (2007)

More than 5 million Americans have dementia, a leading cause of death among persons older than 65 years in the United States. Eating problems typically develop during the advanced stage of dementia, which requires decision making to direct care toward either palliation or more aggressive measures, such as tube feeding. The case of Mr P, a 93-year-old man with end-stage dementia and recent hip fracture, illustrates the issues involved in this challenging crossroads when his daughter is confronted with his failure to orally maintain adequate hydration and nutrition. The discussion reviews the epidemiology and natural history of advanced dementia, the barriers to providing palliative care to patients with this condition, the role of pharmacotherapy, and the treatment options for feeding problems and the advantages and disadvantages of each option, and suggests an approach to help clinicians provide effective and compassionate decision support to patients with advanced dementia and their family members.
Antiplatelet Therapy for Ischemic Heart Disease
Authors: Richard A. Lange, L. David Hillis
Journal: New England Journal of Medicine (2004)

Rupture or injury of an atherosclerotic coronary arterial plaque — as occurs spontaneously in patients with an acute coronary syndrome or as the result of a percutaneous coronary intervention — serves as a nidus for platelet aggregation and thrombus formation, which, in turn, may cause myocardial infarction or death. Activation of the platelet-surface glycoprotein IIb/IIIa receptor is the final common pathway in the process leading to platelet aggregation and, eventually, thrombus formation. When this receptor is activated, circulating fibrinogen binds to it and cross-links with adjacent platelets to create a platelet–fibrinogen matrix. Since platelets have a pivotal role in the . . .
BENIGN LESIONS OF THE FEMALE BREAST SIMULATING CANCER
Authors: MAX CUTLER
Journal: JAMA (1933)

Authorities on the subject of neoplasms of the breast are agreed that radical excision constitutes the accepted method for the treatment of all tumors of the breast which exhibit the clinical signs of cancer. This attitude has brought into prominence a group of innocent lesions of the breast accompanied by such classic signs of cancer as to lead to their radical removal under erroneous diagnoses. As the education of the laity has progressed and patients consult their physicians more often soon after the first signs of disease, the task and responsibility of the physician have been greatly increased both in diagnosis and in treatment.  It is the purpose of this communication to describe several innocent states of the breast which simulate cancer and discuss the diagnosis and treatment of some borderline conditions the exact nature and future course of which it is becoming increasingly difficult to estimate as they are
The Pathology of Liver Allograft Surving Longer Than One Year
Authors: Raouf E. Nakhleh, Sarah J. Schwarzenberg, Joseph Bloomer, William Payne, Dale C. Snover
Journal: Hepatology (1990)

Although prolonged survival after liver transplantation is now common, the condition of allografts after prolonged survival has not been widely discussed. We reviewed 86 biopsy samples from 38 patients. The samples were obtained between 366 and 1,622 days after transplant. Thirteen patients' biopsy samples were normal or showed minor changes. Six patients' samples showed rejection. Four patients, including two with rejection, demonstrated ischemic change. Three patients showed focal fibrosis, polymorphonuclear infiltration and bile duct proliferation simulating biliary obstruction, although biliary stones were found in only one patient. Three patients had acute hepatitis. Seven patients had a pattern of chronic persistent hepatitis; four had chronic active hepatitis. Follow–up biopsy samples were obtained in seven chronic hepatitis patients. Two of the patients with chronic active hepatitis have shown slight progression of the disease. None has progressed to cirrhosis, but neither has the chronic active hepatitis resolved. It is likely that some of these cases represent non–A, non–B hepatitis. Although histological abnormalities are common after successful transplantation, the clinical significance of many of the changes remains to be determined. Only patients with rejection or vascular thromboses required new transplants.(Hepatology 1990;11:465-470.)
Ontogeny and Sorafenib Metabolism
Authors: Eric I. Zimmerman, Justin L. Roberts, Lie Li, David Finkelstein, Alice Gibson, Amarjit S. Chaudhry, Erin G. Schuetz, Jeffrey E. Rubnitz, Hiroto Inaba, Sharyn D. Baker
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To investigate the role of ontogeny in sorafenib metabolism to the equipotent active metabolite sorafenib N-oxide. Experimental Design: Steady-state pharmacokinetic studies of sorafenib and metabolites were conducted in 30 children and young adults (17 males; median age, 9.5 years) receiving sorafenib 150 mg/m2 or 200 mg/m2 twice daily. Sorafenib metabolism was evaluated in vitro at 10 μmol/L using a panel of purified human cytochrome P450 (CYP) enzymes. Sorafenib metabolism and CYP3A4 expression was evaluated in 52 human liver samples from donors of ≤20 years old. The drug–drug interaction potential between sorafenib and azole antifungal agents was evaluated in vitro and in vivo. Results: No age-related differences in sorafenib apparent oral clearance were observed. Mean sorafenib N-oxide metabolite ratio was 0.27 ± 0.14. In children of ≤10 years of age, boys had approximately 2-fold higher N-oxide ratios than girls (0.40 ± 0.15 vs. 0.22 ± 0.12, P = 0.026). Of the CYPs evaluated, sorafenib was exclusively metabolized to sorafenib N-oxide by CYP3A4. A trend for increased N-oxide formation in boys was observed in liver samples, which correlated with CYP3A4 mRNA expression. Posaconazole and voriconazole potently inhibited sorafenib N-oxide formation in vitro, and reduced sorafenib N-oxide formation in 3 children given sorafenib concurrent with azoles. Conclusion: We have identified several factors affecting interpatient variability in sorafenib metabolism to the active N-oxide metabolite including age, sex, and concurrent treatment with azole antifungals. This knowledge may provide important considerations for the clinical use of sorafenib in children and possibly other kinase inhibitors undergoing CYP3A4-mediated metabolism. Clin Cancer Res; 18(20); 5788–95. ©2012 AACR.
Clinical presentation of severe anemia in pediatric patients with sickle cell anemia seen in Enugu, Nigeria
Authors: A.I. Juwah, A. Nlemadim, W. Kaine
Journal: American Journal of Hematology (2003)

Anemia is a major cause of morbidity and mortality among patients with sickle cell anemia. In this study, 108 episodes of severe anemia were prospectively evaluated in 108 patients with hemoglobin SS disease attending the pediatric sickle cell clinic of the University of Nigeria Teaching Hospital, Enugu, Nigeria. Young children between the ages of 2 and 4 years were found to be at the greatest risk of developing anemic crises (severe anemia). There was a gradual but progressive decline in the incidence of severe anemia in the age range 8-16 years old. Upper respiratory tract infections are the most commonly associated infections in patients with severe anemia. Others included malaria, septicemia, urinary tract infection, acute chest syndrome, and osteomyelitis. Their role in precipitating episodes of severe anemia among the patients studied could not be fully evaluated. Pallor, jaundice, and fever were the most commonly encountered symptoms in patients with severe anemia on admission. About half of the parents/guardians failed to notice severe anemia among the patients studied, perhaps due to the dark color of the African skin. Caregivers need to be educated on how to recognize anemia among patients with sickle cell anemia when they develop febrile episodes.
Autopsy—Current Issues
Authors: Michael Soman
Journal: JAMA (1987)

To the Editor.—  A recent issue ofJAMAcontains a Council on Scientific Affairs report entitled Autopsy: A Comprehensive Review of Current Issues.1After noting the declining rate of autopsy over the past several decades, the report attempts both to identify the reasons for the decline and to make recommendations to promote the use of autopsy in medicine.  We feel this review failed to recognize several issues regarding autopsy that have an impact on residency training. Residents are strongly encouraged by many attending physicians to obtain autopsies whenever possible. We have seen physicians mislead grieving families (telling them that an autopsy might help clarify the cause of death when this cause was known with near certainty) and intimidate families (with the idea that it might be something genetic).  Despite having heard all of the logical and intellectually satisfying arguments about why autopsies are desirable, many physicians have difficulty justifying
HE NATURAL HISTORY OF LIPID PLAQUES: LONGITUDINAL OBSERVATION AT BASELINE, 6 MONTHS, AND 12 MONTHS USING OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND
Authors: Lei Xing, Jingbo Hou, Haibo Jia, zhigang han, Soo-Joong Kim, Koji Kato, Taishi Yonetsu, Shaosong Zhang, Bo Yu, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2012)
Medicare Nonpayment, Hospital Falls, and Unintended Consequences
Authors: Sharon K. Inouye, Cynthia J. Brown, Mary E. Tinetti
Journal: New England Journal of Medicine (2009)

In 2005, in response to disturbing and widely cited findings by the Institute of Medicine about the prevalence of life-threatening conditions acquired by patients in U.S. hospitals, Congress authorized the Centers for Medicare and Medicaid Services (CMS) to implement payment changes designed to encourage the prevention of such conditions. Under an amendment to the Social Security Act that was enacted on January 1, 2007, the secretary of Health and Human Services was required to identify at least two hospital-acquired conditions by October 1, 2007, that were high-cost, high-volume, or both; that resulted in the assignment of a case to a . . .
Pomalidomide: the new immunomodulatory agent for the treatment of multiple myeloma
Authors: A A Chanan-Khan, A Swaika, A Paulus, S K Kumar, J R Mikhael, S V Rajkumar, A Dispenzieri, M Q Lacy
Journal: Blood Cancer Journal (2013)

In this report, we provide a comprehensive review on the preclinical and clinical investigations conducted in development of the next-generation immunomodulatory drug (IMiD) pomalidomide for the treatment of relapsed/refractory multiple myeloma (MM). We consulted PubMed, MEDLINE, ASH, ASCO annual symposium abstracts and http://clinicaltrials.gov/ for the purpose of this literature review. Twenty-six preclinical and 11 clinical studies were examined. These studies delineate the mechanisms of action of pomalidomide and attest to the robust clinical activity in relapsed/refractory MM. MM is the second most common hematological malignancy in the US. Despite availability of several therapeutic agents, MM remains incurable. Thus, the development of new therapies remains a priority. Pomalidomide is the newest member of the IMiDs class of drugs, and in preclinical and clinical investigations, it has demonstrated an improved efficacy and toxicity profile in comparison to its sister compounds, lenalidomide and thalidomide. Importantly, recent clinical studies have demonstrated its activity in relapsed or refractory myeloma, particularly in lenalidomide and bortezomib-refractory patients. Thus, the addition of pomalidomide to the anti-myeloma armamentarium is widely anticipated to have a significant impact on the overall clinical outcome of advanced stage relapsed and refractory MM patients.
Hepatic Niemann-Pick C1-like 1: The canalicular side of the coin
Authors: Michele Petruzzelli, Antonio Moschetta, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2007)

Abstract Niemann-Pick C1-like 1 (NPC1L1) is required for cholesterol absorption. Intestinal NPC1L1 appears to be a target of ezetimibe, a cholesterol absorption inhibitor that effectively lowers plasma LDL-cholesterol in humans. However, human liver also expresses NPC1L1. Hepatic function of NPC1L1 was previously unknown, but we recently discovered that NPC1L1 localizes to the canalicular membrane of primate hepatocytes and that NPC1L1 facilitates cholesterol uptake in hepatoma cells. Based upon these findings, we hypothesized that hepatic NPC1L1 allows the retention of biliary cholesterol by hepatocytes and that ezetimibe disrupts hepatic function of NPC1L1. To test this hypothesis, transgenic mice expressing human NPC1L1 in hepatocytes (L1-Tg mice) were created. Hepatic overexpression of NPC1L1 resulted in a 10- to 20-fold decrease in biliary cholesterol concentration, but not phospholipid and bile acid concentrations. This decrease was associated with a 30%–60% increase in plasma cholesterol, mainly because of the accumulation of apoE-rich HDL. Biliary and plasma cholesterol concentrations in these animals were virtually returned to normal with ezetimibe treatment. These findings suggest that in humans, ezetimibe may reduce plasma cholesterol by inhibiting NPC1L1 function in both intestine and liver, and hepatic NPC1L1 may have evolved to protect the body from excessive biliary loss of cholesterol.