tbuckley/cabot-search huggingface dataset:
Hodgkin's Disease
Authors: Sol Levy
Journal: New England Journal of Medicine (1945)

SINCE Hodgkin's1 original description in 1832 of the disease known by his name, many papers have appeared in the medical literature that attempt to clarify both the etiology and pathology as well as the symptomatology of this illness.So far as the etiology is concerned, the cause of the disease still remains unknown, although two main theories have been put forward to explain its origin.2 The first holds that the changes in the lymphoid tissues are the result of an infection, the disease thus being a specific infective granuloma of unknown origin. The second theory, on the other hand, considers . . .
EXCISION OF DISEASED EYEBALL, FOLLOWED BY RELIEF OF REFLEX CEREBRAL SYMPTOMS.Read in the Section on Ophthalmology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: H. MOULTON
Journal: JAMA (1891)

The following case seems rather unique, hence is reported: Mr. R., æt. 40, single, and a farmer, was sent to me May 19, 1890, by Dr. Thomas, of Booneville, Ark. When 6 years old, some lye thrown into his right eye had destroyed its sight. The eye then gave no special trouble until twenty years afterwards, when it became inflamed and ruptured, discharging the lens and part of the vitreous. During the past twelve years it has been subject to occasional attacks of pain, mild at first, but becoming more severe and of greater frequency. For a year or more the patient has suffered from almost constant frontal headache. During the past eight months, insomnia and symptoms of mental aberration were added. The mental trouble assumed the form of melancholy. The patient became suspicious of his friends, fearing bodily and other injury at their hands, and attempted on several occasions
Blood lactate concentrations during incremental work before and after maximum exercise.
Authors: H. A. Davis, G. C. Gass
Journal: British Journal of Sports Medicine (1979)

Five male subjects performed three successive incremental work tests on an electronically braked cycle ergometer. The first and second tests were separated by thirty minutes of rest, the second and third by three minutes of maximum work. During the third test, venous blood lactate concentrations were still decreasing at work rates where they were increasing during the first two tests. The work rate at which rapid increases in lactate concentrations occurred during the final test coincided with the work rate where rapid increases occurred in the two initial tests. It was concluded that this point represented a threshold where a balance existed between removal and release of lactate from and into the plasma compartment, and did not coincide with the anaerobic threshold. It is postulated that steady state work at levels above this threshold would result in a continuous increase in venous lactate concentration.
Genetic effect of CCR3 and IL5RA gene polymorphisms on eosinophilia in asthmatic patients
Authors: June-Hyuk Lee, Hun Soo Chang, Ji Hyun Kim, Se-Min Park, Yong Mok Lee, Soo Taek Uh, Taiyoun Rhim, Il Yup Chung, Yong-Hoon Kim, Byung Lae Park, Choon-Sik Park, Hyoung Doo Shin
Journal: Journal of Allergy and Clinical Immunology (2007)
Should Informed Consent for Cancer Treatment Include a Discussion about Hospital Outcome Disparities?
Authors: Nadine Housri, Robert J Weil, David I Shalowitz, Leonidas G Koniaris
Journal: PLoS Medicine (2008)

Several studies have found disparities in the outcome of medical procedures across different hospitals--better outcomes have been associated with higher procedure volume. An Institute of Medicine workshop found such a "volume-outcome relationship" for two types of cancer surgery: resection of the pancreas and esophagus (http://www.iom.edu/?id=31508). This debate examines whether physicians have an ethical obligation to inform patients of hospital outcome disparities for these cancers.
Aerosols in Chronic Airway Obstruction
Authors: Charles E. Reed
Journal: New England Journal of Medicine (1986)

Clinicians treating chronic airway obstruction can now choose from so varied a menu of therapies that the choice often becomes bewilderingly difficult. Some connoisseurs are beginning to think that bronchodilators should be listed among the appetizers or side dishes rather than among the entrees, because bronchoconstriction is only one component of intrathoracic airway obstruction. Other components include edema and inflammation of the bronchial wall in asthma and chronic bronchitis, loss of elastic recoil in emphysema, mucus-gland hypertrophy in asthma and chronic bronchitis, smooth-muscle hypertrophy in asthma, and loss of function in the mucociliary escalator with an accumulation of secretions behind . . .
Epidemiology of Anencephalus and Spina Bifida
Authors: Godfrey P. Oakley
Journal: JAMA (1980)

In Western societies, congenital malformations are the leading cause of infant mortality. In some countries, we are approaching the time when improvements in infant mortality can come only from improvement in mortality associated with malformations. The vast majority of epidemiologic studies of infant mortality have sought predictors by looking for associations between various factors and total infant mortality. Infant mortality is not, however, a single disease, but many diseases. There is little wonder that our approach so far has not been productive. What would we learn of the epidemiology of the infectious diseases if we always considered them to be a single entity? We must move from studies of all infant mortality to studies of specific causes. It is heartening that the Elwood brothers have produced such a splendid example of the kind of cause-specific infant mortality epidemiology that is so badly needed. I highly recommend this volume to those
Evolution of Cryptosporidium parvum Lactate Dehydrogenase from Malate Dehydrogenase by a Very Recent Event of Gene Duplication
Authors: D. Madern
Journal: Molecular Biology and Evolution (2003)

We have expressed the L-lactate dehydrogenase (LDH) and L-malate dehydrogenase (malDH) genes from the apicomplexan Cryptosporidium parvum (CpLDH1 and CpMalDH1) as maltose-binding protein (MBP) fusion proteins in Escherichia coli. The substrate specificities, enzymatic kinetics, and oligomeric states of these two parasite enzymes have been characterized. By taking advantage of recently completed and ongoing apicomplexan genome sequencing projects, we identified additional MalDH genes from Plasmodium spp., Toxoplasma gondii, and Eimeria tenella that were previously unavailable. All apicomplexan MalDHs appeared to be cytosolic and no organellar homologs were identified from the completely sequenced P. falciparum genome and other ongoing apicomplexan genome-sequencing projects. Using these expanded apicomplexan LDH and MalDH sequence databases, we reexamined their phylogenetic relationships and reconfirmed their relationship to α-proteobacterial MalDHs. All LDH and MalDH enzymes from apicomplexans were monophyletic within the LDH-like MalDH group (i.e., MalDH resembling LDH) as a sister to α-proteobacterial MalDHs. All apicomplexan LDHs, with the exception of CpLDH1, formed a separate clade from their MalDH counterparts, indicating that these LDHs were evolved from an ancestral apicomplexan MalDH by a gene duplication coupled with functional conversion before the expansion of apicomplexans. Finally, CpLDH1 was consistently placed together with CpMalDH1 within the apicomplexan MalDH cluster, confirming an early working hypothesis that CpLDH1 was probably evolved from the same ancestor of CpMalDH1 by a very recent gene duplication that occurred after C. parvum diverged from other apicomplexans.
Effect of dl-ethionine on the intestinal absorption and transport of palmitic acid-1-14C and tripalmitin-14C. Role of intramucosal factors in the uptake of luminal lipids
Authors: Jacques I. Kessler, S. Mishkin, J. Stein
Journal: Journal of Clinical Investigation (1969)

The effect of DL-ethionine on the uptake and transport of lipid by the rat small intestine was investigated. A cottonseed oil emulsion containing (14)C-labeled tripalmitin or palmitic acid was administered intragastrically to rats pretreated with DL-ethionine, DL-ethionine plus methionine, or saline, and the rats were sacrificed 2, 4, and 6 hr later. Lipids from the plasma, the stomach, the colon, the luminal contents of the small intestine, and the wall of the small intestine were extracted, fractionated, and their radioactivity assayed. Ethionine markedly inhibited the uptake of lipids by the small intestine. This inhibition was not related to impairment of intraluminal lipolysis since analagous inhibitions were observed when palmitic acid or predigested triglyceride (TG), obtained through a jejunal fistula from normal animals, was administered instead of tripalmitin. Ethionine also inhibited the transport of lipid from the wall of the small intestine. A significant fraction of the administered lipid remained in the wall of the small intestine, and only a small fraction was transported to the blood stream. Although most of the wall radioactivity was in the form of TG, significant proportions were also found in the free fatty acid (FFA) and partial glyceride fractions, indicating a marked inhibition of mucosal reesterification to TG. The degree of inhibition of mucosal reesterification and the degree of inhibition of transport of wall lipids were directly related to the degree of inhibition of uptake of luminal radioactivity. This relationship suggests that the rate of reesterification, the level of mucosal FFA, and the rate of transport of intramucosal TG may be of importance in determining the extent of uptake of intraluminal lipid by the mucosal cells. Since a significant fraction of the wall radioactivity was in the form of TG, the decreased transport of wall lipids was attributed to an impairment of chylomicron completion due to inhibition of either the synthesis of chylomicron apoprotein or the association of preformed TG with the protein moiety of chylomicrons. Experiments with labeled amino acids support the first possibility.
PTU-128 Temporary double-dosing with infliximab: quick fix or long term solution?
Authors: P M Irving, S Shinhmar, J Duncan, M Sastrillo, S Anderson, J Sanderson, J O Lindsay
Journal: Gut (2012)

<h3>Introduction</h3> The increasing use of anti-TNF drugs in Crohn9s disease reflects their efficacy. Unfortunately, even with scheduled maintenance therapy, secondary loss of response is common affecting approximately 10%–15% of patients/year. Increasing drug levels, whether by doubling the dose or decreasing the interval, recaptures response in approximately 75% of patients. However, both of these strategies have cost implications. Anecdotal reports suggest that in patients losing response on maintenance infliximab (IFX) 5 mg/kg, a temporary increase to double doses (DD; 10 mg/kg) can lead to subsequent recapture of response at the lower dose. In a small cohort, we have previously shown that this strategy was not viable in the majority of patients. We now present an extended cohort across two centres with longer follow-up. <h3>Methods</h3> We performed a retrospective review across two tertiary centres of all patients with Crohn9s disease who had received temporary increases to DD of IFX for loss of response. Demographic data, HBI prior to the first infusion at the higher dose and prior to the first infusion at the lower dose, and ability to continue on IFX at 5 mg/kg were recorded. <h3>Results</h3> 34 patients (18M:16F, median age 24 (range 12–51)) received DD IFX for loss of response. Median disease duration was 3 years (range 0–32) and the median time to dose increase from starting IFX was 12 months (range 3–60). All had received standard induction doses of IFX at 5 mg/kg on weeks 0, 2 and 6 and were on scheduled maintenance therapy. The dose interval prior to dose increase was 8 weeks for 24 patients, 7 weeks for 1, and 6 weeks for 9. 26 patients were on concurrent immunomodulators and 8 were not. One patient received 4 DD, 27 received 2 DD and six patients 1 DD. Dose increase was effective in the short term with the median HBI falling from 6 (range 0–27) prior to the first infusion at 10 mg/kg, to 1 (0–7) prior to the first infusion back at the standard dose (5 mg/kg) (p=0.003). However, only seven patients remained on IFX at the end of follow-up (median 13 months (range 8–25)). The median interval to discontinuing IFX was 4 months after the first DD (1–19). Of those who discontinued, four had infusion reactions while the others failed to maintain a response to IFX. <h3>Conclusion</h3> Because of the limited treatment options available in Crohn9s disease, attempting to recapture response in patients on IFX is appropriate. However, while temporary double-dosing is effective in the short term, it does not deliver long term disease control after subsequent dose reduction. Whether dose reduction is possible after prolonged dose increase remains to be answered. <h3>Competing interests</h3> None declared.
Regulation of Animal Experimentation
Authors: Thomas D. Overcast
Journal: JAMA (1985)

This article examines the nature of the controversy between animal activists and the scientific community over the need for and desirability of additional regulation of animal experimentation. We critically review the existing federal and state regulatory environment and discuss a number of proposals for new federal legislation for regulating the use of animals in scientific experimentation. We identify and discuss three factors that encompass the issues that are at the core of the controversy and use these to suggest a conceptual framework in which to analyze schemes for regulating animal experimentation. Finally, we discuss the implications that such regulation will have for animal experimentation and conclude that it is neither necessary nor desirable. (<i>JAMA</i>1985;254:1944-1949)
Incipient Angiogenesis in Barrett’s Epithelium and Lymphangiogenesis in Barrett’s Adenocarcinoma
Authors: Merja I. Auvinen, Eero I.T. Sihvo, Terhi Ruohtula, Jukka T. Salminen, Aki Koivistoinen, Päivi Siivola, Ragna Rönnholm, Juhani O. Rämö, Mathias Bergman, Jarmo A. Salo
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Barrett’s esophagus (BE), a precancerous condition for Barrett’s adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barrett’s adenocarcinoma patients is the frequent development of lymph node metastases. We addressed whether onset of angiogenesis occurs in BE and if the lymphatic system might provide a route for Barrett’s adenocarcinoma cells to infiltrate regular lymph nodes. PATIENTS AND METHODS: Fifteen surgically resected Barrett’s dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used. RESULTS: The incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barrett’s epithelium, giving its ominous salmon-red color. Barrett’s epithelium–specific goblet cells express vascular endothelial growth factor (VEGF)-A. The immature blood vessels show a relative absence of smooth muscle actin (SMA)-positive mural cells and express VEGF receptor (VEGFR)-2 and matrix metalloproteinase (MMP)-9 on their exterior. Coexpression of VEGF-C and its receptor VEGFR-3 on lymphatic vessels is demonstrated. CONCLUSION: BE is strongly neovascularized not eroded. This novel concept of a molecular mechanism of the origin of BE might emphasize why precancerous BE can give rise to the more cancerous dysplasia and Barrett’s adenocarcinoma stages. In addition, adenocarcinoma cells induce lymphangiogenesis. The new lymphangiogenic vessels might provide a systemic route for adenocarcinoma cells to invade circulation and induce lymph node metastasis.
Tissue Engineering of Heart Valves
Authors: Erwin Rieder, Gernot Seebacher, Marie-Theres Kasimir, Eva Eichmair, Birgitta Winter, Barbara Dekan, Ernst Wolner, Paul Simon, Guenter Weigel
Journal: Circulation (2005)

Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction.Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88+/-0.19% versus 30.20+/-3.93% migrated cells [mean+/-SEM]; cusps, 0.10+/-0.06% versus 10.24+/-1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (wall, 5.03+/-0.14% versus 24.31+/-2.38%; cusps, 3.18+/-0.38% versus 10.24+/-1.83%). SDS-PAGE of the pulmonary heart valve tissue revealed that considerable amounts of proteins with different molecular weights that were not detected in the human equivalent remain in the decellularized porcine heart valve.We describe for the first time that the remaining potential of decellularized pulmonary heart valves to attract monocytic cells depends strongly on whether porcine or human scaffolds were used. These findings will have an important impact on further investigations in the field of heart valve tissue engineering.
Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice
Authors: Leman Yalcintepe, Arthur E. Frankel, Donna E. Hogge
Journal: Blood (2006)
Image-Guided Cardiac Cell Delivery Using High-Resolution Small-Animal Ultrasound
Authors: Martin Rodriguez-Porcel, Olivier Gheysens, Ian Y. Chen, Joseph C. Wu, Sanjiv Sam Gambhir
Journal: Molecular Therapy (2005)

Open-chest cardiac injection is the preferred delivery method for cardiac gene and stem cell therapy in small animals, but it is invasive and the operator is unable to see the actual delivery site. High-resolution ultrasound has recently been developed for small-animal imaging. We tested the hypothesis that image-guided cardiac cell delivery using high-resolution ultrasound guidance is feasible and reproducible. Sprague–Dawley rats (n = 11) were imaged using high-resolution ultrasound, and stably transfected cardiomyoblasts (plasmid–CMV–firefly luciferase) were injected into the anterior cardiac wall under ultrasound guidance (parasternal long-axis view), using a 28-gauge needle. After injection, bioluminescence imaging was performed using a cooled charged-coupled camera. Injection was successful in all animals and was associated with no mortality. The signal detected was positively correlated with the amount of cells transplanted (R2 = 0.94, P = 0.03) and highly correlated with ex vivo assays (R2 = 0.82). In addition, the optical signal could be followed longitudinally using bioluminescence imaging. Ultrasound image-guided cardiac cell delivery is an effective, safe, and reproducible way to perform cell delivery to a specific myocardial region and can be combined with assessment of cardiac function. We are confident that the use of these technologies will play a significant role in the future of gene and cell therapy.
Babies born at 37-38 weeks lag academically eight years later
Authors: J. H. Tanne
Journal: BMJ (2012)

Babies who are born “at term,” but early, lag in school achievement eight years later, concludes a study of 128 050 singleton pregnancies in New York by researchers from Columbia University.1

“Term” is usually considered to be 37-41 weeks of gestation. The researchers, led by Kimberly Noble, found that school achievement at age 8 was significantly lower among children born at 37-38 weeks than among those born at 39-41 weeks.

The retrospective study used data from New York city’s Department of Health and Mental Hygiene and Department of Education. The study included all singleton births to mothers living in New York city from 1988 to 1992 and those children who eight years later …
Deworming programme in India sparks controversy
Authors: G. Mudur
Journal: BMJ (2015)

<h3>Objective</h3> Nearly 20%–29% of patients with colorectal cancer (CRC) succumb to liver or lung metastasis and there is a dire need for novel targets to improve the survival of patients with metastasis. The long isoform of the Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1-L or CC1-L) is a key regulator of immune surveillance in primary CRC, but its role in metastasis remains largely unexplored. We have examined how CC1-L expression impacts on colon cancer liver metastasis. <h3>Design</h3> Murine MC38 transfected with CC1-L were evaluated in vitro for proliferation, migration and invasion, and for in vivo experimental liver metastasis. Using shRNA silencing or pharmacological inhibition, we delineated the role in liver metastasis of Chemokine (C-C motif) Ligand 2 (CCL2) and Signal Transducer and Activator of Transcription 3 (STAT3) downstream of CC1-L. We further assessed the clinical relevance of these findings in a cohort of patients with CRC. <h3>Results</h3> MC38-CC1-L-expressing cells exhibited significantly reduced in vivo liver metastasis and displayed decreased CCL2 chemokine secretion and reduced STAT3 activity. Down-modulation of CCL2 expression and pharmacological inhibition of STAT3 activity in MC38 cells led to reduced cell invasion capacity and decreased liver metastasis. The clinical relevance of our findings is illustrated by the fact that high CC1 expression in patients with CRC combined with some inflammation-regulated and STAT3-regulated genes correlate with improved 10-year survival. <h3>Conclusions</h3> CC1-L regulates inflammation and STAT3 signalling and contributes to the maintenance of a less-invasive CRC metastatic phenotype of poorly differentiated carcinomas.
[624] ALBUMIN INTERFERON ALFA-2b DOSED AT Q2W OR Q4W INTERVALS DEMONSTRATES COMPARABLE WEEK 12 EFFICACY RESPONSE IN IFN NAIVE, GENOTYPE-1 RAPID VIRAL RESPONDERS
Authors: A.U. Neumann, L. Rozenberg, S. Zeuzem, Y. Benhamou, J. McHutchison, E. Pulkstenis, M. Subramanian
Journal: Journal of Hepatology (2007)