tbuckley/cabot-search huggingface dataset:
Lessons Learned From Fatal Progressive Multifocal Leukoencephalopathy in a Patient With Multiple Sclerosis Treated With Natalizumab
Authors: Aaron L. Boster, Jacqueline A. Nicholas, Ilir Topalli, Yaz Y. Kisanuki, Wei Pei, Bethanie Morgan-Followell, Claudia F. Kirsch, Michael K. Racke, David Pitt
Journal: JAMA Neurology (2013)

To describe the clinical, radiological, and histopathological features of a fatal case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis treated with natalizumab. We will use this case to review PML risk stratification and diagnosis.Case report.Tertiary referral center hospitalized care.A 55-year-old, JC virus (JCV) antibody-positive patient with multiple sclerosis who died of PML after receiving 45 infusions of natalizumab.Brain magnetic resonance imaging and cerebrospinal fluid JCV DNA polymerase chain reaction results.The patient developed subacute onset of bilateral blindness following his 44th dose of natalizumab. Ophthalmologic examination was normal, the brain magnetic resonance imaging was not suggestive of PML, and cerebrospinal fluid analysis did not reveal the presence of JCV DNA. The patient was subsequently treated for a presumed multiple sclerosis relapse with high-dose corticosteroids. Two weeks after his 45th dose of natalizumab, he developed hemiplegia that evolved into quadriparesis. Repeated magnetic resonance imaging and cerebrospinal fluid studies were diagnostic for PML. Postmortem histopathological analysis demonstrated PML-associated white matter and cortical demyelination.The risks and benefits of natalizumab must be reassessed with continued therapy duration. When there is high clinical suspicion for PML in the setting of negative test results, close clinical vigilance is indicated, natalizumab treatment should be suspended, and JCV polymerase chain reaction testing and brain magnetic resonance imaging scans should be repeated.
Hypohaptoglobinemia associated with familial epilepsy.
Authors: S S Panter, S M Sadrzadeh, P E Hallaway, J L Haines, V E Anderson, J W Eaton
Journal: The Journal of Experimental Medicine (1985)

In select kindreds afflicted with familial idiopathic epilepsy, most individuals suffering seizures also have low levels of the plasma hemoglobin-binding protein, haptoglobin. This hypohaptoglobinemia may be causally associated with a tendency to develop epilepsy. Our experimental results indicate that artificially-induced hypohaptoglobinemia in mice causes retarded clearance of free hemoglobin from the central nervous system, and that such free hemoglobin may engender the peroxidation of brain lipids. We hypothesize that hypohaptoglobinemia, either inherited, or acquired via traumatic processes, may prevent efficient clearance of interstitial hemoglobin from the central nervous system, thereby predisposing these people to encephalic inflammation and the appearance of seizure disorders.
More excess needed. Occasionally
Authors: E. Davies
Journal: BMJ (2012)

Many of the difficulties in the US healthcare system revolve around excess. There is the caricatured excessive energy consumption of its patients, of course, but also the excess of the entire system.

Two weeks ago this column flagged up the excessive and increasing proportion of gross national product going toward healthcare across the country (www.bmj.com/content/345/bmj.e7127?ijkey=WvGIF8lkG3h11qi&keytype=ref). Two months ago we published an investigation into the excessive treatment of patients in America (www.bmj.com/content/345/bmj.e6230). And this week the theme resurfaced in …
Acidic Triterpenes Compromise Growth and Survival of Astrocytoma Cell Lines by Regulating Reactive Oxygen Species Accumulation
Authors: Rubén Martín, Juliana Carvalho, Elvira Ibeas, Marita Hernández, Valentina Ruiz-Gutierrez, María Luisa Nieto
Journal: Cancer Research (2007)

Abstract Several studies have shown how pentacyclic triterpenes can inhibit proliferation and induce apoptosis of some tumor cell lines; however, its effect on astrocytic tumors, one of the most malignant forms of cancer, has rarely been reported. The aim of this study was to examine how the pentacyclic triterpenes, oleanolic acid and maslinic acid, isolated from olive juice, affected astrocytoma cell morphology and survival. Cell proliferation was inhibited in 1321N1 astrocytoma cells by using 1 to 50 μmol/L of either oleanolic acid or maslinic acid, with an average IC50 of 25 μmol/L. Growth inhibition led to morphologic and cytoskeletal alterations associated with the loss of stellate morphology and characterized by a retraction of the cytoplasm and collapse of actin stress fibers. Using 4′,6-diamidino-2-phenylindole and Annexin V, we showed that astrocytoma cell death induced by oleanolic acid or maslinic acid were mainly due to apoptotic events. Furthermore, we showed that caspase-3 is activated as a consequence of triterpene treatment. Finally, we found that exposure of the cells to oleanolic acid or maslinic acid resulted in a significant increase of intracellular reactive oxygen species, followed by loss of mitochondrial membrane integrity. Importantly, enzymatic scavengers, such as catalase, or phenolic antioxidants, such as butylated hydroxytoluene, rescued cells from the triterpene-mediated apoptosis, suggesting that the potential therapeutic effect of these acidic triterpenes is dependent on oxidative stress. Our data show that acidic triterpenes play a major role in 1321N1 astrocytoma morphology and viability and support the conclusion that oleanolic acid and maslinic acid may thus be promising new agents in the management of astrocytomas. [Cancer Res 2007;67(8):3741–51]
Oral quinine for the treatment of uncomplicated malaria
Authors: H. Reyburn, G. Mtove, I. Hendriksen, L. v. Seidlein
Journal: BMJ (2009)

Is ineffective in outpatients and should be used only in rare cases Artemisinin combination therapy is the first line treatment for uncomplicated malaria in nearly all malaria endemic countries in subSaharan Africa.This treatment is relatively expensive, but it kills parasites faster than any other method and has few adverse effects.1The combination artemetherlumefantrine (Coartem) is coformulated, can be taken in a convenient schedule over three days, and is popular with patients and healthcare providers.2The linked study by Achan and coworkers (
Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study
Authors: Christel Depienne, Marianna Bugiani, Céline Dupuits, Damien Galanaud, Valérie Touitou, Nienke Postma, Carola van Berkel, Emiel Polder, Eleonore Tollard, Frédéric Darios, Alexis Brice, Christine E de Die-Smulders, Johannes S Vles, Adeline Vanderver, Graziella Uziel, Cengiz Yalcinkaya, Suzanna G Frints, Vera M Kalscheuer, Jan Klooster, Maarten Kamermans, Truus EM Abbink, Nicole I Wolf, Frédéric Sedel, Marjo S van der Knaap
Journal: The Lancet Neurology (2013)
WESTERN DISPENSARY, SUPPURATION OF THE SUBMAXILLARY GLAND FROM IRRITATION PRODUCED BY A FOREIGN BODY
Authors: T. W. Nunn
Journal: BMJ (1856)

ground, he heard a crack, and found himself unable to iwk.He was then brought here.The left ankle is very much hurt.Both the external and the internal malleoli arc fractured, and the foot turned inwards.The skin over the ankle and foot is not, however, broken.The sole of the foot looks upwards, the dislocation being inwards.It appears as if the calcis had been torn away from the astragalus, though it is hardly probable that this was the case.The parts seem very much swollen, and all movement of them exceedingly panful.The ankle was covered with an evaporating lotion, and perfect rest enjoined.Dec. 2nd.Ten leeches were applied, and warm fomenta- tions ordered, the pain and swelling being very great.Dec. 3rd.Patient has slept better; still a good deal of pain about the joint: foot still a little turned in.The skin over the inner ankle is inflamed, and large blebs are making their appearance.Dec. 7th.More leeches were necessary, and were re- peated on the 8th and on the 11th.Dec. 29th.Zinc lotion is being used now.The pain about the joint has all gone, as also the swelling; but the heel is a little sore, from resting long in one position.Jan. 2nd, 1856.Better.The heel, having been padded with cotton wool, is less painful.The only spot where pain is felt is just below the outcr ankle.After this time, the case proceeded favourably; and, on Jan. 15th, the cure wvas so inearly completed as to render it probable the patient would soon leave the hospital.II.STRANGULATED FEMORAL HERNIA: OPERATION: DEATH. CASE. Eliz. B
Mediastinal Uptake of 1-131 in a Hiatal Hernia Mimicking Recurrence of Papillary Thyroid Carcinoma
Authors: LINDA L. WILLIS, ROBERT J. COWAN
Journal: Clinical Nuclear Medicine (1993)

1-131 is used to image patients diagnosed with papillary or follicular carcinoma of the thyroid after thyroidectomy to observe for metastatic disease or residual thyroid tissue. 1-131 is excreted in gastric mucosa and is seen in the esophagus after the swallowing of saliva. The authors describe a patient in whom radiopharmaceutical activity in the mediastinum was subsequently shown to be due to a hiatal hernia.
Effect of chronic ethanol intake on lactase activity and active galactose absorption in rat small intestine.
Authors: R Mazzanti, E S Debnam, W J Jenkins
Journal: Gut (1987)

The effects of feeding a nutritionally adequate liquid diet containing 5% ethanol to rats over a four week period on intestinal lactase activity and the kinetics of jejunal galactose absorption in vivo have been determined. Both lactase activity and the maximum capacity for active, saturable galactose absorption (Jmax) were increased significantly after chronic ethanol ingestion. In contrast, uptake of the sugar via the phlorhizin-insensitive (passive) route was unaffected by ethanol. Our results imply the presence of an increased maturity of the enterocyte population on the villus surface in response to ethanol. The relevance of this work to uptake studies in alcoholics is briefly discussed.
Gene Expression Profiles of Hair Root Tissue of Atopic Dermatitis
Authors: A. Yagami, K. Futamura, A. Matsuda, K. Orihara, N. Hashimoto, R. Kojima, H. Morita, K. Sugiura, Y. Muro, Y. Tomita, K. Matsunaga, H. Saito, K. Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2009)
Burden of allergic rhinitis: Results from the Pediatric Allergies in America survey
Authors: Eli O. Meltzer, Michael S. Blaiss, M. Jennifer Derebery, Todd A. Mahr, Bruce R. Gordon, Ketan K. Sheth, A. Larry Simmons, Mark A. Wingertzahn, John M. Boyle
Journal: Journal of Allergy and Clinical Immunology (2009)
Lipid‐Like Nanomaterials for Simultaneous Gene Expression and Silencing In Vivo
Authors: Yizhou Dong, Ahmed A. Eltoukhy, Christopher A. Alabi, Omar F. Khan, Omid Veiseh, J. Robert Dorkin, Sasilada Sirirungruang, Hao Yin, Benjamin C. Tang, Jeisa M. Pelet, Delai Chen, Zhen Gu, Yuan Xue, Robert Langer, Daniel G. Anderson
Journal: Advanced Healthcare Materials (2014)

New lipid-like nanomaterials are developed to simultaneously regulate expression of multiple genes. Self-assembled nanoparticles are capable of efficiently encapsulating pDNA and siRNA. These nanoparticles are shown to induce simultaneous gene expression and silencing both in vitro and in vivo. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Hemoglobin Kenya composed of α‐ and (<sup>A</sup>γβ)‐fusion‐globin chains, associated with hereditary persistence of fetal hemoglobin
Authors: Ibifiri Wilcox, Kevin Boettger, Lance Greene, Anita Malek, Lance Davis, Martin H. Steinberg, Hong‐Yuan Luo, David H.K. Chui
Journal: American Journal of Hematology (2008)

Hb Kenya is made up of two normal alpha-globin chains and two (A)gammabeta-fusion globin chains. The latter are the product of an (A)gammabeta-hybrid globin gene formed as a result of misalignment during meiosis and nonhomologous crossing over. It is associated with a deletion of 22.7 kb including the delta-globin gene, between the (A)gamma- and beta-globin genes. Hb Kenya is found in Kenyans and Ugandans. Heterozygotes have moderately increased Hb F, and this mutation has been known as an ((A)gammabeta)(+) hereditary persistence of fetal hemoglobin (HPFH). Compound heterozygotes for Hb Kenya/Hb S are thought to be asymptomatic, but reports of long term follow-up of these patients are lacking. The correct identification of Hb Kenya is sometimes problematic. In cation exchange high performance liquid chromatography, Hb Kenya elutes in similar position as Hb A(2), Hb Lepore, Hb E, and several other variant hemoglobins. Definitive diagnosis that is necessary for proper patient management is best done by DNA-based gap-PCR tests.
Cost Containment: How Is It to Be Achieved?
Authors: David D. Marcus
Journal: JAMA (1987)

Most strategies for containing health care costs have as their particular target curbing the growth of expenditures for acute-care inpatient services. Medicare has attacked hospital costs from two sides: prospective pricing to control hospital revenue per admission and, through the Peer Review Organization program, constraints on utilization to control the volume of admissions. Private-sector cost-containment programs, while less easy to characterize briefly, have in general headed toward the same primary goal of capping the growth of inpatient expenditures. Many employers are encouraging health maintenance organization enrollment and have imposed both preadmission certification and after-the-fact utilization review on their fee-for-service health insurance programs. As a result of these private- and public-sector efforts, both the occupancy and the capacity of the hospital industry have been declining. American Hospital Association statistics illustrate this trend: in the 12 months ending in March 1986, the number of staffed beds declined by 1.5%, the number of
Postprandial Hyperglycemia and Cardiovascular Disease
Authors: Antonio Ceriello
Journal: Diabetes Care (2009)

In the recent HEART2D (Hyperglycemia and its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus) study, published in this issue of Diabetes Care , Raz et al. (1) try to answer a hotly debated question of the last 10 years: is postprandial hyperglycemia an independent risk factor for cardiovascular disease in diabetes? This question, highlighted recently, has arisen because of the identified linear relationship, widely confirmed in many studies, between the risk of cardiovascular disease death and 2-h oral glucose tolerance test values (2). Consistent with these past results, a recent study has confirmed postprandial hyperglycemia as an independent risk factor for cardiovascular disease in type 2 diabetes (3). At the same time, in the STOP-NIDDM Trial it has been shown, as a predefined secondary end point, that treating postprandial hyperglycemia may reduce the incidence of new cardiovascular events in people with impaired glucose tolerance (4)—a finding confirmed in type 2 diabetes by a meta-analysis on the use of acarbose (5).

Another important issue is that prandial glucose regulation, an emerging approach to treating type 2 diabetes, emphasizes the need for moderating the acute surges in plasma glucose levels that follow meals (6). Mechanistic and epidemiological studies indicate that postprandial glucose significantly contributes to overall glycemic exposure (6). In particular, postprandial hyperglycemia is the most important contributor to A1C, particularly when it is lower than 7.5% (7). Therefore, targeting postprandial hyperglycemia is important for the achievement of A1C targets. Numerous prandial therapeutics are now available, and an ever-growing literature on their use shows …
A Network of PDZ-Containing Proteins Regulates T Cell Polarity and Morphology during Migration and Immunological Synapse Formation
Authors: Mandy J. Ludford-Menting, Jane Oliaro, Faruk Sacirbegovic, Eric T.-Y. Cheah, Natalie Pedersen, Suzanne J. Thomas, Anupama Pasam, Rosa Iazzolino, Lukas E. Dow, Nigel J. Waterhouse, Amanda Murphy, Sarah Ellis, Mark J. Smyth, Michael H. Kershaw, Phillip K. Darcy, Patrick O. Humbert, Sarah M. Russell
Journal: Immunity (2005)
Snapin Mediates Incretin Action and Augments Glucose-Dependent Insulin Secretion
Authors: Woo-Jin Song, Madhav Seshadri, Uzair Ashraf, Thembi Mdluli, Prosenjit Mondal, Meg Keil, Monalisa Azevedo, Lawrence S. Kirschner, Constantine A. Stratakis, Mehboob A. Hussain
Journal: Cell Metabolism (2011)
ANTIBODY-PRODUCING CAPACITY OF ADULT CHICKEN SPLEEN CELLS IN NEWLY HATCHED CHICKS
Authors: Ben W. Papermaster, S. Gaylen Bradley, Dennis W. Watson, Robert A. Good
Journal: The Journal of Experimental Medicine (1962)

1. To evaluate the effect of primary in vitro antigenic stimulation on a population of immunologically competent cells, a homologous cell transfer system was used, with adult chickens as the spleen cell donors, killed Brucella abortus as the antigen, and newly hatched chicks as the recipients. 2. The distribution of antibody titers in recipients of cells from random donors was bimodal, with about 30 per cent showing no detectable titer and the remainder distributed normally. 3. Variability of titer was reduced significantly in subgroups receiving cells from a single donor, indicating that the primary source of variability was the genetic capacity of discrete cell populations to respond to antigen. 4. In serial passage studies, activity of donor cell populations was lost rapidly: antibody was not demonstrated after the second passage, and the graft versus host reaction (splenomegaly) was not demonstrated after the third passage. Results were similar with in vitro antigenic stimulation at the time of the first passage only and with additional stimulation at the time of subsequent transfers. 5. The thesis that,the homograft reaction of the newly hatched recipients had contributed significantly to the variability in the single transfer studies and to the rapid loss of activity in the serial transfer experiments was confirmed by the results of transfers following alteration of the lymphoreticular system of the host by thorotrast administration, splenectomy, and treatment with 19-nortestosterone during embryogenesis. All three favored the survival and function of transferred cells, raising the average antibody titer and virtually eliminating the no-response category. The inhibition of homograft immunity was most pronounced in the 19-nortestosterone group.
Randomised controlled trials in general practice
Authors: M. Pringle, R. Churchill
Journal: BMJ (1995)

Gold standard or fool's gold?

Randomised controlled trials are a widely accepted means of applying experimental methods to a clinical setting and have been advocated as the gold standard for comparing and evaluating different treatments.1 2 General practice has been promoted as an appropriate arena for evaluating interventions ranging from drug treatment to developments in services3 4: nine out of 10 health service consultations take place here; it is the point of first contact for most medical conditions; and existing population registers and computer systems allow potential access to large amounts of clinical data. An increasing number of randomised controlled trials are being performed in this setting to contribute to the culture of evidence based medicine.5 But despite the theoretical attractions, applying experimental methods in clinical practice presents problems that, if not properly addressed or acknowledged, may invalidate the findings.6 The particular problems of recruitment and randomisation merit consideration with respect to primary care. …
Salicylates and Reye's Syndrome-Reply
Authors: Raymond S. Greenberg
Journal: JAMA (1983)

<h3>In Reply.—</h3> We thank Dr Simmons for his suggestion of a further scientific uncertainty connected with the studies of salicylate use and Reye's syndrome. In our<i>JAMA</i>review article and also in the original case-control studies,<sup>1-3</sup>the term<i>salicylate</i>was used as a general label for compounds that are structurally related to salicylic acid. This class of compounds includes acetylsalicylic acid and sodium salicylate as well as other agents such as bismuth subsalicylate. The use of the term<i>salicylate</i>in this general manner is supported by standard pharmacologic references.<sup>4</sup> Dr Simmons speculates that Reye's syndrome may be related to aspirin intake but not to that of other salicylates. At present, there are insufficient data available to assess this hypothesis. Indeed, aspirin was the most commonly administered salicylate in the children with Reye's syndrome,<sup>1-3</sup>but the study sample sizes were too small to detect significant effects for any
Characteristics of electrograms recorded at reentry circuit sites and bystanders during ventricular tachycardia after myocardial infarction
Authors: Dusan Z Kocovic, Tomoo Harada, Peter L Friedman, William G Stevenson
Journal: Journal of the American College of Cardiology (1999)

The purpose of this study was to determine the relation of isolated potentials (IPs) recorded during ventricular tachycardia (VT) to reentry circuit sites identified by entrainment.Reentry circuits causing VT late after myocardial infarction are complex. Both IPs and entrainment have been useful for identifying successful ablation sites, but the relation of IPs to the location in the reentry circuit as determined by entrainment has not been completely defined.Data from catheter mapping of 70 monomorphic VTs in 36 patients with prior myocardial infarction were retrospectively analyzed. Entrainment followed by radiofrequency current (RF) ablation was performed at 384 sites. On the basis of entrainment, sites were classified as reentry circuit exit, central-proximal, inner or outer loop sites. Sites outside the circuit were divided into remote and adjacent bystanders.Isolated potentials were recorded at 50% (51 of 101) of reentry circuit exit, central and proximal sites as compared with only 8% (11 of 146, p < 0.001) of inner loop and outer loop sites and only 1.8% (2 of 106) of remote bystander sites (p < 0.001). Isolated potentials were also present at 45% of adjacent bystander sites. At central and proximal sites the presence of an IP increased the incidence of tachycardia termination by RF to 47.5% from 24% (p = 0.05). At exit sites tachycardia termination occurred frequently regardless of the presence or absence of IPs (45% vs. 48%, p = NS). Isolated potentials at exit, central and proximal sites had a shorter duration at sites where ablation terminated VT than at sites without termination (20.9 +/- 9.6 ms vs. 35.7 +/- 15.3 ms, p < 0.001).Isolated potentials are a useful guide to sites in the central-proximal region of the reentry circuit, but often fail to identify exit sites where ablation is successful. Entrainment and analysis of electrograms provide complementary information during mapping of VT.
An unfortunate mistake: A heartbeat too many
Authors: M J Weston
Journal: BMJ (1997)

Torsade de pointes, torsade de pointes. The phrase kept floating through the back of my mind as I stood on the tenth tee during the golf club's charity day two years ago in May, experiencing runs of fast heart beats which seemed to ebb and flow.

I had been used to tachycardias since my teenage years when a visit to the town's library had led me to suspect Wolf Parkinson White syndrome, later …