tbuckley/cabot-search huggingface dataset:
Initial and Maintenance Digitalization-Reply
Authors: Harold Rosenblum
Journal: JAMA (1963)

<h3>To the Editor:</h3> —Dr. Silber writes that it has been his practice routinely to redigitalize, in 3 or 4 days, those patients who received rapid initial digitalization in the hospital. He states, however, that "When this technique is employed, the incidence of side effects is no greater than when initial digitalization is carried out by conventional methods with oral long-acting glycosides alone." Surely, it must be the aim of the clinician to plan a digitalis-therapy regimen which has the greatest likelihood of avoidance of these potentially serious side effects. Every thoughtful physician knows that the problems of congestive heart failure are not usually solved permanently by a single hospital admission no matter how careful or precise a regimen is planned and recommended. It is pointed out in my study that all such management must be individualized for maximum benefit, and the results obtained were not projected by me into the
The crowd is self-aware
Authors: Judith E. Fan, Jordan W. Suchow
Journal: Behavioral and Brain Sciences (2014)

Abstract Bentley et al.’s framework assigns phenomena of personal and collective decision-making to regions of a dual-axis map. Here, we propose that understanding the collective dynamics of decision-making requires consideration of factors that guide movement across the map. One such factor is self-awareness , which can lead a group to seek out new knowledge and re-position itself on the map.
Helicobacter pyloriinfection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis
Authors: Alexis García, Yan Feng, Nicola MA Parry, Amanda McCabe, Melissa W Mobley, Kvin Lertpiriyapong, Mark T Whary, James G Fox
Journal: Gut Microbes (2013)

Helicobacter pylori (H. pylori) and hepatitis C virus (HCV) infect millions of people and can induce cancer. We investigated if H. pylori infection promoted HCV-associated liver cancer. Helicobacter-free C3B6F1 wild-type (WT) and C3B6F1-Tg(Alb1-HCVN)35Sml (HT) male and female mice were orally inoculated with H. pylori SS1 or sterile media. Mice were euthanized at ~12 mo postinoculation and samples were collected for analyses. There were no significant differences in hepatocellular tumor promotion between WT and HT mice; however, HT female mice developed significantly larger livers with more hepatic steatosis than WT female mice. H. pylori did not colonize the liver nor promote hepatocellular tumors in WT or HT mice. In the stomach, H. pylori induced more corpus lesions in WT and HT female mice than in WT and HT male mice, respectively. The increased corpus pathology in WT and HT female mice was associated with decreased gastric H. pylori colonization, increased gastric and hepatic interferon gamma expression, and increased serum Th1 immune responses against H. pylori. HT male mice appeared to be protected from H. pylori-induced corpus lesions. Furthermore, during gastric H. pylori infection, HT male mice were protected from gastric antral lesions and hepatic steatosis relative to WT male mice and these effects were associated with increased serum TNF-α. Our findings indicate that H. pylori is a gastric pathogen that does not promote hepatocellular cancer and suggest that the HCV transgene is associated with amelioration of specific liver and gastric lesions observed during concurrent H. pylori infection in mice.
The duodenum: a conduit or a pump?
Authors: MICHAEL CAMILLERI
Journal: Gut (1997)

See article on page624 

In the article by Nguyen et al in this issue (see page 624), a novel impedance method was used to characterise the transport of chyme in the duodenum in the postprandial period. The authors suggest that abnormal postprandial transport of chyme in the duodenum may be a factor that results in impairment of gastric emptying in patients with long-standing type I diabetes mellitus. The paper raises a number of interesting issues.

The first question is: does the human duodenum actually perform any hydrostatic or pumping function? In a previous in vitro model, Weems1 suggested that the cat duodenum was incapable of hydrostatic function, in contrast to the ileum. This observation was supported by the very different nature of contractions observed in the mammalian upper small …
3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling
Authors: Daniel G. Sedding, Monique Tröbs, Fabian Reich, Gerhard Walker, Ludger Fink, Werner Haberbosch, Wigbert Rau, Harald Tillmanns, Klaus T. Preissner, Rainer M. Bohle, Alexander C. Langheinrich
Journal: Circulation Research (2009)

3-Deazaadenosine (c3Ado) is a potent inhibitor of S-adenosylhomocysteine hydrolase, which regulates cellular methyltransferase activity. In the present study, we sought to determine the effect of c3Ado on vascular smooth muscle cell (VSMC) function and neointima formation in vivo. c3Ado dose-dependently prevented the proliferation and migration of human coronary VSMCs in vitro. This was accompanied by an increased expression of the cyclin-dependent kinase inhibitors p21(WAF1/Cip1), p27(Kip1), a decreased expression of G(1)/S phase cyclins, and a lack of retinoblastoma protein hyperphosphorylation. In accordance with these findings, fluorescence-activated cell-sorting analysis of propidium iodide-stained cells indicated a cell cycle arrest in the G(0)/G(1) phase. Importantly, c3Ado did not affect the number of viable (trypan blue exclusion) or apoptotic cells (TUNEL). Mechanistically, c3Ado prevented FCS-induced Ras carboxyl methylation and membrane translocation and activity by inhibiting isoprenylcysteine carboxyl methyltransferase and reduced FCS-induced extracellular signal-regulated kinase (ERK)1/2 and Akt phosphorylation in a dose-dependent manner. Conversely, rescuing signal transduction by overexpression of a constitutive active Ras mutant abrogated c3Ado's effect on proliferation. For in vivo studies, the femoral artery of C57BL/6 mice was dilated and mice were fed a diet containing 150 microg of c3Ado per day. c3Ado prevented dilation-induced Ras activation, as well as ERK1/2 and Akt phosphorylation in vivo. At day 21, VSMC proliferation (proliferating-cell nuclear antigen [PCNA]-positive cells), as well as the neointima/media ratio (0.7+/-0.2 versus 1.6+/-0.4; P<0.05) were significantly reduced, without any changes in the number of apoptotic cells. Our data indicate that c3Ado interferes with Ras methylation and function and thereby with mitogenic activation of ERK1/2 and Akt, preventing VSMC cell cycle entry and proliferation and neointima formation in vivo. Thus, therapeutic inhibition of S-adenosylhomocysteine hydrolase by c3Ado may represent a save and effective novel approach to prevent vascular proliferative disease.
Human rights groups plead for protection for hospital patients in Gaza
Authors: Merav Sarig
Journal: BMJ (2007)

<h3>Background</h3> Raltitrexed is approved for the treatment of advanced colorectal cancer when there is a contraindication to fluoropyrimidines. Compared to different regimens of 5-fluorouracil and folinic acid, no better results were observed in terms of overall survival (OS). However, it was associated with greater toxicity and worse quality of life. <h3>Purpose</h3> To assess the use of raltitrexed in the treatment of metastatic colorectal cancer. <h3>Material and methods</h3> Observational, retrospective study of patients treated with raltitrexed in monotherapy from January 2014 to June 2017. The data collected, obtained from the chemotherapy prescription programme and the electronic medical record, were: sex, age, previous chemotherapy regimens, treatment duration and reason for discontinuation, adverse events (AEs), dose modifications and death date. Efficacy was measured in terms of progression-free survival (PFS) and OS. <h3>Results</h3> Forty patients, 29 males (72.5%), with a median age of 66 years (43–85) were treated with raltitrexed in monotherapy. The medians of previous chemotherapy regimens, administered cycles and duration of treatment were respectively: 3 (0–5); 3 (1–10) and 48 days (23–283). Reasons for interruption were: progression (n=30 (70%), six of which were sent to the palliative care unit), bad performance status (n=7 (17.5%)) and serious toxicity (asthaenia n=2 (5%); and neutropaenia grade 4 n=1 (2.5%)). The median PFS was 1.6 months (0.9–2.8) and the median OS was 6.6 months (4.3–12.1). The reported AEs were: anaemia (n=12 (30%)), vomiting and diarrhoea (n=5 (12.5%)), asthaenia (n=4 (10%)), neutropaenia (n=3 (7.5%)), thrombocytopaenia (n=2 (5%)) and liver enzymes alteration (n=2 (5%)). Dose reduction was required due to AEs in six patients (15%). Seventeen patients (42.5%) suffered some type of haematological toxicity of any degree. <h3>Conclusion</h3> The predominance of males in this study matches the highest incidence in this sex. AEs were similar to those described in the literature, with a higher incidence of haematological toxicity. The large percentage of patients with any AE, the reasons for treatment discontinuation and dose reductions may be related to the high number of previous regimens administered. All this invites reflection on the use of chemotherapy in situations where support treatment would be indicated. <h3>References and/or acknowledgements</h3> Popov I, et al. Raltitrexed versus standard leucovorin-modulated bolus 5-fluorouracil: PETACC-1. <i>Eur J Cancer</i> 2008;44:2204–11. No conflict of interest.
Otx dose-dependent integrated control of antero-posterior and dorso-ventral patterning of midbrain
Authors: Eduardo Puelles, Dario Acampora, Emmanuel Lacroix, Massimo Signore, Alessandro Annino, Francesca Tuorto, Stefania Filosa, Giorgio Corte, Wolfgang Wurst, Siew-Lan Ang, Antonio Simeone
Journal: Nature Neuroscience (2003)
Diaschisis as the Presenting Feature in Sporadic Creutzfeldt-Jakob Disease
Authors: Daryl Wile, Harinder Dhaliwal, Justyna R. Sarna, Christine P. Molnar, James N. Scott, Fiona Costello, Sarah Furtado, Jeffrey T. Joseph
Journal: JAMA Neurology (2013)

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The Association of Radiographically Detected Vertebral Fractures with Back Pain and Function: A Prospective Study
Authors: Michael C. Nevitt
Journal: Annals of Internal Medicine (1998)

Background: Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of these fractures remains uncertain. Objective: To determine the association of new vertebral fractures with back pain and back-related functional limitation in older women. Design: Prospective observational study. Setting: Multicenter Study of Osteoporotic Fractures. Participants: 7223 white women aged 65 years and older. Measurements: Lateral spine radiographs were obtained at baseline and at a follow-up examination an average of 3.7 years later. Prevalent and incident radiographic vertebral fractures were assessed by quantitative morphometry. Frequency and severity of back pain, disability in doing six activities involving the back, and days of bed rest and days of limited activity due to back pain were assessed annually by questionnaire during follow-up. Results: Among women without a vertebral fracture at baseline, those with at least one incident vertebral fracture were more likely to have increased back pain (odds ratio [OR], 2.4 [95% CI, 1.7 to 3.3]) and back disability (OR, 2.6 [CI, 1.9 to 3.7]) and at least 1 day of bed rest due to back pain (OR, 6.7 [CI, 4.4 to 10.2]) and 7 days of limited activity due to back pain per year (OR, 3.8 [CI, 2.7 to 5.0]). Among women with a fracture at baseline, those with an incident vertebral fracture also had a greater risk for increased back pain (OR, 2.0 [CI, 1.4 to 2.8]) and back disability (OR, 2.2 [CI, 1.5 to 3.1]) and at least 1 day of bed rest (OR, 7.9 [CI, 4.9 to 12.9]) and 7 days of limited activity per year (OR, 3.5 [CI, 2.4 to 5.0]). Women with incident fracture had about 10 additional limited-activity days and 1 to 2 days of bed rest per year. New vertebral fractures that did not come to medical attention were associated with increased back pain and functional limitation. Conclusion: New vertebral fractures, even those not recognized clinically, are associated with substantial increases in back pain and functional limitation due to back pain in older white women. Prevention of new vertebral fractures should reduce the burden of back pain and functional limitation in women with vertebral osteoporosis.
Should folic acid fortification be mandatory? Yes
Authors: Nicholas J Wald, Godfrey P Oakley
Journal: BMJ (2007)

The UK9s Food Standards Agency recently recommended mandatory folic acid fortification of some foods. <b>Nicholas Wald</b> and <b>Godfrey Oakley</b> argue that it9s a safe effective way of preventing spina bifida and anencephaly—but <b>Richard Hubner and colleagues</b> say that more research into the harms is needed
Amyotrophic Lateral Sclerosis and Glutamate — Too Much of a Good Thing?
Authors: Dennis W. Choi
Journal: New England Journal of Medicine (1992)

The dicarboxylic amino acid glutamate is not only an essential amino acid but also a signaling substance, serving as a workhorse neurotransmitter at many excitatory synapses in the central nervous system. Glutamate is present in millimolar concentrations throughout the brain and spinal cord, mostly in the presynaptic terminals of excitatory neurons, and it exerts a powerful neuroexcitant action on virtually all central neurons. Normally, glutamatergic transmission is a closely controlled process; the release and cellular reuptake of glutamate are carefully regulated, so that neurons are exposed to it only briefly and at low levels appropriate for synaptic neurotransmission or neurotrophic . . .
Self-Support of Medical Sciences Through Patents
Authors: Gilbert Dalldorf
Journal: JAMA (1976)

THE ASSETS of many foundations are shrinking at a time when federal dispensations have tightened. As a result, wholly independent resources for support of medical research are now more attractive, if not more essential, than ever. An opportunity for self-support that is often neglected is income from commercially useful discoveries. An example is the substantial royalty income realized from nystatin, a patented antibiotic. Nystatin had been discovered in the laboratories of the Division of Laboratories and Research of the New York State Department of Health by two members of the scientific staff, Elizabeth Hazen, PhD, a mycologist, and Rachel Brown, PhD, a biochemist. They had christened it nystatin to commemorate its parent, the New York state laboratory. It is better known by one of its trade names, Mycostatin, suggested by the manufacturer to signify its cardinal activity, the inactivation of various fungi. The discovery raised various technical problems and one
Molecular Analysis of the High-Hemoglobin-F Phenotype in Saudi Arabian Sickle Cell Anemia
Authors: Barbara A. Miller, Nancy Olivieri, Mohammed Salameh, Mohammed Ahmed, Giovanna Antognetti, Titus H.J. Huisman, David G. Nathan, Stuart H. Orkin
Journal: New England Journal of Medicine (1987)

Patients from the eastern province of Saudi Arabia who have sickle cell anemia have high circulating levels of fetal hemoglobin (hemoglobin F, 17 percent), and they therefore have a mild form of the disease. To examine the molecular basis of the elevated production of hemoglobin F, we searched for mutations in the promoter regions of the two hemoglobin F gamma-globin genes (G gamma and A gamma). The DNA sequences 450 bp (base pairs) upstream of both the G gamma and A gamma globin genes were normal except for a single-base cytosine-to-thymidine (C----T) substitution at -158 bp 5' to the cap (preinitiation) site of the G gamma-globin gene of the high-hemoglobin-F chromosome. We searched for an association between this -158 C----T substitution and the production of hemoglobin F and G gamma in normal Saudis and Saudis with sickle cell disease or trait. The substitution was present in nearly 100 percent of the patients with sickle cell disease or trait, and in 22 percent of the normal Saudis. Homozygosity for this mutation had no demonstrable effect on hemoglobin F production in the normal Saudi population. We conclude that this mutation is not uniquely responsible for the increase in hemoglobin F in Saudi patients. It may nevertheless have an important role in regulating hemoglobin F production, but its expression is complex and requires interaction with additional factors, such as hemolytic stress or other molecular determinants, possibly linked to the sickle cell gene.
ABC of clinical haematology: Chronic myeloid leukaemia
Authors: J. Goldman
Journal: BMJ (1997)

Chronic myeloid leukaemia is a clonal malignant myeloproliferative disorder believed to originate in a single abnormal haemopoietic stem cell.The progeny of this abnormal stem cell proliferate over months or years such that, by the time the leukaemia is diagnosed, the number of leucocytes is greatly increased in the peripheral blood.Normal blood cell production is almost completely replaced by leukaemia cells, which, however, still function almost normally.Chronic myeloid leukaemia has an annual incidence of 1 to 1.5 per 100 000 of the population in the United Kingdom (about 700 new cases each year), with no clear geographical variation.Presentation may be at any age, but the peak incidence is at age 40-60 years, with a slight male predominance.This leukaemia is very rare in children.Most cases of chronic myeloid leukaemia occur sporadically.The only known predisposing factor is irradiation, as shown by studies of Japanese survivors of the atomic bomb and in patients who received radiotherapy for ankylosing spondylitis.The clinical course of chronic myeloid leukaemia can be divided into a "stable" or chronic phase and an advanced phase, the latter covering both accelerated and blastic phases.Most patients present with chronic phase disease, which lasts on average four to five years.In about two thirds of patients the chronic phase transforms gradually into an accelerated phase, characterised by a moderate increase in blast cells, increasing anaemia or thrombocytosis, or other features not compatible with chronic phase disease.After a variable number of months this accelerated phase progresses to frank acute blastic transformation.The remaining one third of patients move abruptly from chronic phase to an acute blastic phase (or blastic crisis) without an intervening phase of acceleration.
Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody.
Authors: J Lesley, Q He, K Miyake, A Hamann, R Hyman, P W Kincade
Journal: The Journal of Experimental Medicine (1992)

The CD44-negative T lymphoma AKR1 (CD44.2 genotype) was transfected with a CD44.1 cDNA. The intact cDNA conferred on the transfected cells the ability to bind hyaluronic acid (HA) both from solution and immobilized on culture plates. It also conferred a CD44-dependent and hyaluronidase-sensitive increase in adhesion to a lymph node endothelial cell line. A mutant cDNA which codes for a CD44 molecule lacking most of the cytoplasmic domain of CD44 was also transfected into AKR1, and cell sorting was used to select transfectants expressing levels of cell surface CD44 expression comparable with the line transfected with the wild-type CD44 cDNA. The cells transfected with the mutant construct bound fluoresceinated HA from solution very poorly, but did adhere to immobilized HA, though less well than cells transfected with the wild-type construct. This result indicates that the cytoplasmic domain of CD44 is necessary for binding of HA from solution but is not required for binding to immobilized HA, although it may contribute to adhesion following ligand recognition. A monoclonal antibody (mAb), IRAWB 14, which reacts with CD44 on all CD44+ cells dramatically induced HA binding by some CD44+ cell lines that did not constitutively bind HA. The transfectant expressing a CD44 molecule with a truncated cytoplasmic domain could be induced by this antibody to bind fluoresceinated-HA from solution. Splenic T cells did not bind fluoresceinated HA constitutively. In the presence of the IRAWB 14 mAb, virtually all CD44+ splenic T cells bound HA. Induction was immediate and occurred equally well at room temperature and at 4 degrees C, indicating that the new HA-binding activity was due to preexistent CD44 molecules. These results are compatible with an antibody-induced activation of CD44 by either a conformational change in the CD44 molecule or a change in the distribution of CD44 molecules on the cell surface.
APPEARANCE OF ANTI-ACETYLCHOLINE RECEPTOR ANTIBODIES COINCIDENT WITH ONSET OF MYASTHENIC WEAKNESS IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Guido Valesini, Rosella Pastore, Pier Guiseppe De Berardinis, Umberto Serafini, Angela Vincent, Gian Franco Bottazzo
Journal: The Lancet (1983)
Noncultured, Autologous, Skeletal Muscle Cells Can Successfully Engraft Into Ovine Myocardium
Authors: Nicolas Borenstein, Patrick Bruneval, Mehrak Hekmati, Christophe Bovin, Luc Behr, Christian Pinset, François Laborde, Didier Montarras
Journal: Circulation (2003)

Background— There is compelling evidence showing that cellular cardiomyoplasty can improve cardiac function. Considering the potential benefit of using noncultured muscle cells (little time, lower cost, reduced risk of contamination), we investigated the feasibility of grafting cells obtained directly after enzymatic dissociation of skeletal muscle biopsies into ovine myocardium. We hypothesized that those noncultured muscle cells would engraft massively. Methods and Results— Autologous, intramyocardial skeletal muscle cell implantation was performed in 8 sheep. A skeletal muscle biopsy sample (≈10 g) was explanted from each animal. The sheep were left to recover for ≈3 hours and reanesthetized when the cells were ready for implantation. A left fifth intercostal thoracotomy was performed, and 10 epicardial injections of the muscle preparation (between 10 and 20 million cells) were carried out. All sheep were euthanized 3 weeks after myocardial implantation. Immunohistochemistry was performed with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. Skeletal myosin heavy-chain expression was detected in all slides at 3 weeks after implantation in 8 of 8 animals, confirming engraftment of skeletal muscle cells. Massive areas of engraftment (from 2 to 9 mm in diameter) or discrete loci were noted within the myocardial wall. Conclusions— Our results indicate that noncultured skeletal muscle cells can successfully and massively engraft in ovine myocardium. Thus, avoiding the cell culture expansion phase is feasible and could become a promising option for cellular cardiomyoplasty.