tbuckley/cabot-search huggingface dataset:
No Hypoglycemia After Subcutaneous Administration of Glucagon-Like Peptide-1 in Lean Type 2 Diabetic Patients and in Patients With Diabetes Secondary to Chronic Pancreatitis
Authors: Filip K. Knop, Tina Vilsbøll, Steen Larsen, Sten Madsbad, Jens J. Holst, Thure Krarup
Journal: Diabetes Care (2003)

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 ± 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity. RESEARCH DESIGN AND METHODS—Eight lean type 2 diabetic patients (group 1) aged 60 years (range 50–72) with BMI 23.1 kg/m2 (20.3–25.5) and HbA1c 8.0% (6.9–11.4) and eight patients with type 2 diabetes secondary to chronic pancreatitis (group 2) aged 52 years (41–62) with BMI 21.9 kg/m2 (17.6–27.3) and HbA1c 7.8% (6.2–12.4) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body wt. Then, 15 min later, at the time of peak GLP-1 concentration, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. HOMA (mean ± SEM) showed insulin resistance amounting to 1.9 ± 0.3 and 1.7 ± 0.5 in the two groups, respectively. RESULTS—In both groups, PG decreased rapidly and stabilized at 7.5 mmol/l (range 3.9–10.1) and 7.2 mmol/l (3.1–10.9) in groups 1 and 2, respectively, after 90 min. Neither symptoms of hypoglycemia nor biochemical hypoglycemia were observed in any patient. CONCLUSIONS—We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.
Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-κB pathway and promotes lymphomagenesis
Authors: Cornelia Hömig-Hölzel, Caroline Hojer, Julia Rastelli, Stefano Casola, Lothar J. Strobl, Werner Müller, Leticia Quintanilla-Martinez, Andreas Gewies, Jürgen Ruland, Klaus Rajewsky, Ursula Zimber-Strobl
Journal: The Journal of Experimental Medicine (2008)

CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell–dependent immune responses. Because CD40 is widely expressed on the surface of tumor cells in various B cell malignancies, deregulated CD40 signaling has been suggested to contribute to lymphomagenesis. In this study, we show that B cell-specific expression of a constitutively active CD40 receptor, in the form of a latent membrane protein 1 (LMP1)/CD40 chimeric protein, promoted an increase in the number of follicular and marginal zone B cells in secondary lymphoid organs in transgenic mice. The B cells displayed an activated phenotype, prolonged survival and increased proliferation, but were significantly impaired in T cell-dependent immune responses. Constitutive CD40 signaling in B cells induced selective and constitutive activation of the noncanonical NF-κB pathway and the mitogen-activated protein kinases Jnk and extracellular signal–regulated kinase. LMP1/CD40-expressing mice older than 12 mo developed B cell lymphomas of mono- or oligoclonal origin at high incidence, thus showing that the interplay of the signaling pathways induced by constitutive CD40 signaling is sufficient to initiate a tumorigenic process, ultimately leading to the development of B cell lymphomas.
A PAPER THAT CHANGED MY PRACTICE
Authors: D. Mowat
Journal: BMJ (1995)

General practitioners whose educational experiences have embraced Michael Balint's work and the Leeuwenhorst “physical, emotional, and social” description of our job tend to favour longer consultations and to value the time spent with those patients wishing to unravel psychological problems. This results in surgeries which run and finish late, frustrated patients who endure longer waiting times, and embattled receptionists who undergo difficult mornings.

The work of John Howie and his colleagues shows the possibility of rearranging consulting time so that instead …
The Eye and Systemic Disease
Authors: Arnall Patz
Journal: JAMA (1975)

This volume is a compendium of papers presented at an International Symposium conducted by the Department of Ophthalmology in Iowa City. The participants are recognized authorities in their respective fields, and the subjects covered constitute some of the principal ophthalmic problems related to systemic disorders. The topics selected include the hereditary systemic metabolic diseases, the collagen and rheumatic diseases, nutritional diseases, endocrine disorders, diabetic retinopathy, hypertension and retinal vascular accidents, the hematologic and reticuloendothelial diseases, gastrointestinal disorders, and dermatological diseases affecting the eye. Newell, in the summarizing chapter, provides a concise and constructive review of the material presented and outlines potential areas of new investigation. The quality of the material is generally excellent. In the various chapters, there are several tables helpful in describing clinical features and differential diagnoses. The panel discussions are quite useful and provide a constructive and critical appraisal by the participants of each section presented. I
Targets still lead care in emergency departments
Authors: S. Mason, J. Nicholl, T. Locker
Journal: BMJ (2010)

The UK four hour standard for processing patients attending emergency departments was introduced at 90% in 2004 and has sat at 98% since 2005. We have shown that the effect of the target is not uniform—patients admitted to hospital from the emergency department were affected most by a “spike” in activity during the …
Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1)
Authors: Richard J. Holt, Youming Zhang, Aristea Binia, Anna L. Dixon, Claire Vandiedonck, William O. Cookson, Julian C. Knight, Miriam F. Moffatt
Journal: Journal of Allergy and Clinical Immunology (2011)
Differential regulation of constitutive androstane receptor expression by hepatocyte nuclear factor4α isoforms
Authors: Jean Marc Pascussi, Agnes Robert, Amelie Moreau, Jeanne Ramos, Paulette Bioulac‐Sage, Francis Navarro, Pierre Blanc, Eric Assenat, Patrick Maurel, Marie Jose Vilarem
Journal: Hepatology (2007)

Constitutive androstane receptor (CAR; NR1I3) controls the metabolism and elimination of endogenous and exogenous toxic compounds by up-regulating a battery of genes. In this work, we analyzed the expression of human CAR (hCAR) in normal liver during development and in hepatocellular carcinoma (HCC) and investigated the effect of hepatocyte nuclear factor 4α isoforms (HNF4α1 and HNF4α7) on the hCAR gene promoter. By performing functional analysis of hCAR 5′-deletions including mutants, chromatin immunoprecipitation in human hepatocytes, electromobility shift and cotransfection assays, we identified a functional and species-conserved HNF4α response element (DR1: ccAGGCCTtTGCCCTga) at nucleotide −144. Both HNF4α isoforms bind to this element with similar affinity. However, HNF4α1 strongly enhanced hCAR promoter activity whereas HNF4α7 was a poor activator and acted as a repressor of HNF4α1-mediated transactivation of the hCAR promoter. PGC1α stimulated both HNF4α1-mediated and HNF4α7-mediated hCAR transactivation to the same extent, whereas SRC1 exhibited a marked specificity for HNF4α1. Transduction of human hepatocytes by HNF4α7-expressing lentivirus confirmed this finding. In addition, we observed a positive correlation between CAR and HNF4α1 mRNA levels in human liver samples during development, and an inverse correlation between CAR and HNF4α7 mRNA levels in HCC. These observations suggest that HNF4α1 positively regulates hCAR expression in normal developing and adult livers, whereas HNF4α7 represses hCAR gene expression in HCC. (HEPATOLOGY 2007;45:1146–1153.)
Abstract 4227: Curcumin in cyclodextrin in liposome as a delivery vehicle against osteosarcoma
Authors: Santosh S. Dhule, Patrice Penfornis, Trivia Frazier, Ryan Walker, Grace Tan, Jibao He, Vijay John, Radhika Pochampally
Journal: Cancer Research (2011)

Abstract The delivery of curcumin, a broad spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma. Osteosarcoma (OS) accounts for approximately 20% of all bone cancers and it develops during the period of rapid growth in adolescence. Anti-cancer potential of curcumin has not been fully explored in the form of nanoformulations against OS. The drug is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential evaluated against OS and breast cancer. The resulting 2-Hydroxypropyl-gamma-cyclodextrin/curcumin-liposome complex shows promising anticancer potential against cancer of mesenchymal and epithelial origin when tested against KHOS and MCF-7 cell lines with IC50 value of 5.4 and 10.2 µg/ml respectively. The anticancer potential of curcumin in the form of DCL (drug-in-cyclodextrin-in-liposome) preparation has been explored first time for OS. DMSO-curcumin (free drug) induced autophagic cell death in KHOS whereas liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro and in vivo also. The in vivo study was performed using human osteosarcoma xenograft model in mice. Interestingly, liposomal curcumin was less toxic on normal cells. In this study, the objective to cause cancer cell death by apoptosis and not by autophagy was achieved through liposomal curcumin formulations alone. 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 4227. doi:10.1158/1538-7445.AM2011-4227
Education, Occupation, and Alzheimer's Disease
Authors: Artiss L. Powell
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The article by Dr Stern and colleagues<sup>1</sup>reports an important relationship between risk for AD and education, a relationship that came under scrutiny following the report of Zhang et al.<sup>2</sup>Subsequent reports have suggested a protective role of education, possibly through increased neuronal synapse density.<sup>3</sup> For several decades, computational neuroscientists, cognitive psychologists, and computer scientists have incorporated anatomical and physiological data into neural network computer simulations to replicate<sup>4</sup>and, more recently, to study<sup>5,6</sup>brain function. In general, neural network development can be separated into three phases (design, training, and testing) with simple models usually constructed with at least three layers: input (I), hidden units (HUs), and output (0). The I layer is equivalent to a sensory system such as vision, while HUs correlate with association cortices. Hidden units are sandwiched between the I and O layers with the I output serving as the
Computed tomography angiography in patients with tuberculous meningitis
Authors: Balwant Singh, Ravindra Kumar Garg, Maneesh Kumar Singh, Rajesh Verma, Hardeep Singh Malhotra, Ameeta Jain, Ragini Singh, Neera Kohli, Rajendra V. Phadke, Rakesh Shukla, Anit Parihar
Journal: Journal of Infection (2012)
A Malaria Chart
Authors: P. Manson
Journal: BMJ (1894)

THE value of the temperature chart and of similar graphic methodb of projecting clinical observations is universally admitt-d.Such methods greatly facilitate the recording, and still more the comprehenEion and comparison of the facts in the clinical tableau.The " malaria chart " is an attempt to apply the same principle, so far as the nature of the subjpct will permit, to the recording in cases of malarial fever of the types and varying phases of the malaria organism along with, and in comparison with, the fluctuations of body temperature.The scientific and pra?tical value of such a chart is obvious.It is believed that after a little practice these combined records will be as easily made and read as those of temperature alone, and it is hoped that they will be of assistance in unravelling some of the many difficulties and obscurities at present connected with the malaria question.So far as concerns the figures of the malaria parasite given in the coloured plate, the compiler lays no claim to originality.These are taken from the works of Laveran, (3olgi, Marchiafava, Bignami, and Mannaberg.and were selected as being probably the best illustrations of the malaria parasite we possess.
Pharmacological Modulation of Prefrontal Cortical Activity During a Working Memory Task in Young and Older Humans: A PET Study With Physostigmine
Authors: Ulderico Freo, Emiliano Ricciardi, Pietro Pietrini, Mark B. Schapiro, Stanley I. Rapoport, Maura L. Furey
Journal: American Journal of Psychiatry (2005)

Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system.In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [15O]H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest. In all subjects, the first two scans were obtained during intravenous saline infusion. Seven young and eight older subjects then received intravenous infusion of physostigmine, a cholinesterase inhibitor, and the remaining six young and five older subjects continued to receive saline.In the placebo condition, task-specific rCBF increases in prefrontal regions were observed in the right middle and inferior frontal cortices in young subjects and in more anterior and ventral prefrontal regions in older individuals. Physostigmine during the working memory task significantly improved performance in both age groups. The right prefrontal regions that were selectively recruited in each age group during the placebo condition showed significantly lower rCBF during physostigmine administration.Cholinergic enhancement does not affect structurally defined cortical regions but rather modulates neural activity in functionally defined regions, that is, in task-related prefrontal cortical areas that are selectively and distinctively recruited in young and older subjects.
Systemic hemodynamics, vasoactive systems, and plasma volume in patients with severe Budd-Chiari syndrome
Authors: Manuel Hernández‐Guerra, Eric López, Pablo Bellot, Carlos Piera, Juan Turnes, Juan G. Abraldes, Jaime Bosch, Juan C. García‐Pagán
Journal: Hepatology (2005)

Budd-Chiari syndrome (BCS) causes postsinusoidal portal hypertension, which leads to complications similar to those observed in cirrhosis. However, no studies have investigated whether patients with BCS develop the hyperdynamic circulatory syndrome present in patients with cirrhosis who have portal hypertension. We evaluated systemic and cardiopulmonary hemodynamics, plasma renin activity, aldosterone and norepinephrine levels, and plasma volume in patients with BCS admitted for complications of portal hypertension. BCS patients had mean systemic and cardiopulmonary pressures and cardiac indices that were within the normal range but were significantly different from those of a group of patients with cirrhosis matched by sex, body surface, and liver function (cardiac index 3.1 ± 0.7 vs. 4.9 ± 1.2 L · min−1 · m−2; P < .001; systemic vascular resistance [SVR] index, 2,189 ± 736 vs. 1,377 ± 422 dyne · s · cm−5 · m−2, P < .001). Despite normal systemic vascular resistance, BCS patients had activation of the neurohumoral vasoactive systems, as evidenced by increased plasma renin activity, aldosterone and norepinephrine levels (15.0 ± 21.5 ng/mL · h, 76.7 ± 106.8 ng/dL, 586 ± 868 pg/mL; respectively) and plasma volume expansion. The analysis of individual BCS patients identified that 7 of the 21 patients actually had reduced SVR index. These patients had the greatest plasma volume expansion. A significant inverse correlation between plasma volume and SVR index was observed. In conclusion, patients with BCS had activation of vasoactive neurohumoral systems and expanded plasma volume. This outcome was observed even though most of these patients did not exhibit systemic vasodilation and cardiac output was not increased, in marked contrast with what is observed in patients with cirrhosis. (HEPATOLOGY 2006;43:27–33.)
Dysfunctional high-density lipoproteins in children with chronic kidney disease
Authors: Ryohei Kaseda, Kathy Jabs, Tracy E. Hunley, Deborah Jones, Aihua Bian, Ryan M. Allen, Kasey C. Vickers, Patricia G. Yancey, MacRae F. Linton, Sergio Fazio, Valentina Kon
Journal: Metabolism (2014)
CHYLOUS ASCITBS WITH EOSINOPHILIA.AN ANALYSIS OF REPORTED CASES.
Authors: L. NAPOLEON BOSTON
Journal: JAMA (1905)

Entering on the subject of chylous ascites, it appears necessary that we consider both chylous and chyloid effusions into the peritoneal cavity, since these two forms of ascites are dependent on entirely different pathologic processes. True chylous ascites results from the escape of chyle into the peritoneal cavity, this condition resulting from some obstruction to the chyliferous channels. A variety of pathologic conditions may be responsible for the effusion of chyle into the peritoneal cavity; and among these may be mentioned traumatism to the abdomen with rupture of the receptaculum chyli, or of the thoracic duct; obstruction to the flow of chyle through its normal channels, e. g., organic heart disease, as a result of which there is stasis of the innominate vein and venous congestion of the liver; venous thrombosis and peritoneal adhesions surrounding and compressing the thoracic duct, pressure of mediastinal tumors on the thoracic duct; abdominal tumors
TREATMENT OF PERNICIOUS ANAEMIA BY LIVER
Authors: H. F. Brewer, A. Q. Wells, F. R. Fraser
Journal: BMJ (1928)

Minot and Murphy' reported that they had obtained good results in the treatment of pernicious anaemia by means of a generous diet rich in animal proteins and especially-in liver, and a year later they published a further report2 on a series of 105 cases.In their second report they confirmed the good results obtained and emphasized the importance of the liver in the diet, and they were further able to announce that a non-protein 0--_--1 4 3 OAYS 0 S /0 I-20 2' 30 JO35 #0 fS JO Jd O6 CHART .-CaseI.
Involuntary Jaw Movements in Elderly Patients
Authors: Mark A. Amdur
Journal: JAMA (1977)

To  Editor.—  Dr Laskin makes two points that merit further comment.  First, he notes that abnormal jaw movements may be caused by factors unrelated to ingestion of major tranquilizers. This fact seems to be frequently forgotten in  controversy over tardive dyskinesia in clinical psychiatry. Registered with our aftercare program is a woman who has been receiving major tranquilizers for many years. She demonstrates  oral-buccal-lingual movements said to be typical of tardive dyskinesia. An admission note from another hospital in 1951 describes identical abnormal movements. Major tranquilizers were introduced into her drug regimen in 1954. Major tranquilizers cannot be implicated in every instance of a psychiatric patient who experiences abnormal jaw movements.  Secondly,  author states that in cases of drug-induced movement disorders, the problem can be eliminated by discontinuing therapy with  drug. Drug discontinuation in  face of apparent tardive dyskinesia is a complex issue with
234 FUNCTIONAL MAGNETIC RESONANCE IMAGING AND STROOP TEST TO STUDY FRONTAL CORTICAL FUNCTION IN PATIENTS WITH CIRRHOSIS AND MINIMAL HEPATIC ENCEPHALOPATHY
Authors: E. Rodríguez, G. Pereira, G. Mónica, O. Laura, L. Rami, C. Falcón, P. Ginès
Journal: Journal of Hepatology (2013)
Improving relatives' consent to organ donation
Authors: T. J Shafer
Journal: BMJ (2009)

Most factors involved in the process can be modified to increase success

Obtaining consent from families for organ donation is the most important element of a successful transplant programme. In a recent large study of donor and non-donor families, 57% of families were predisposed to donate, 17% were unsure, and 25% were not in favour.1 The challenge is to secure consent from those people who are predisposed to donate, convert a substantial proportion of those who are unsure, and convert a smaller proportion of those who are initially not in favour. In the right circumstances this approach can achieve an 80% consent rate.

In the linked systematic review (doi:10.1136/bmj.b991), Simpkin and colleagues identify modifiable factors that influence relatives’ decisions to allow organ donation. They conclude that modifying the process of requesting consent may be the best way to increase organ donation rates in the United Kingdom.2 In a review published in the BMJ earlier this year, Rithalia and colleagues assess the effect of presumed consent legislation on organ donation rates and review data on attitudes towards presumed consent. Although many European countries have opted for presumed consent legislation in an effort to increase organ donation, the review shows that this legislation alone is unlikely to explain the variation in organ donation rates between countries, and multiple factors are probably at play because countries do not always follow their legislation strictly.3

Most factors involved in the consent process and outcome are modifiable. We now know much more about why families donate and factors that can increase consent rates.1 4 Best practices to increase organ donation have been accomplished through the recent US Department of Health Human Services Organ Donation Breakthrough Collaborative—organ donation increased by a cumulative 22.5% from October 2003 to October 2006.5 6 7 …