tbuckley/cabot-search huggingface dataset:
A Tiny Step Closer to Personalized Risk Prediction for Breast Cancer
Authors: Peter Devilee, Matti A. Rookus
Journal: New England Journal of Medicine (2010)

The completion of the first draft sequence of the Human Genome Project in 2001 heralded the arrival of personalized medicine, in which the risk and course of a disease can be predicted on the basis of a person's genotype. During the past 5 years, several genomewide association studies have reported associations between single-nucleotide polymorphisms (SNPs) and common (or "complex") diseases such as diabetes, cardiovascular diseases, and cancer. More recently, however, the promises of these studies have been tempered by disappointment and caution.1,2 A case in point is breast cancer. In this issue of the Journal, Wacholder et al.3 report . . .
Glucose reabsorption from bile. Evidence for a biliohepatic circulation.
Authors: P Guzelian, J L Boyer
Journal: Journal of Clinical Investigation (1974)

Glucose is absent from human bile and present in low concentrations in bile from the rat. To study the mechanisms of this blood-bile glucose concentration difference, infusions of glucose were administered i.v. to 300-400 g male Sprague-Dawley rats with ligated renal pedicles and to two postcholecystectomy patients with indwelling t-tubes. Glucose was assayed in plasma, bile, and rat liver by a hexokinase method specific for D-glucose. In man, glucose was detected in bile when plasma glucose increased above 350 mg/100 ml. In animals studies, low concentrations of bile glucose were observed at plasma levels between 100 and 300 mg/100 ml. However, when plasma concentrations increased between 400 and 900 mg/100 ml, glucose appeared more rapidly in bile, defining by extrapolation an apparent plasma glucose threshold of 280 mg/100 ml. Intraportal phlorizin, a competitive inhibitor of glucose transport, significantly increased bile glucose concentrations. Plasma-bile concentration differences were also observed in rats after i.v. [3-14C]O-methyl glucose (3-O-MG) but not after [3H]mannitol. Hepatic glucose levels were never lower than plasma levels and liver-plasma 3-O-MG ratios were 0.92 +/- 0.22 indicating that entry of glucose and 3-O-MG into hepatocyte water was not limiting. Furthermore, when sodium dehydrocholate augmented canalicular secretion, biliary glucose excretion increased proportionally suggesting that glucose entry into bile was not impeded. When estimates of hepatic glucose secretion were compared with biliary glucose excretion, the latter increased progressively when estimated secretion rates exceeded 50 micrograms/min or when phlorizin was given. Finally, during bile stop-flow experiments, [3-14C]O-MG and [14C]glucose were selectively removed from bile compared with [3H]mannitol. The findings suggest that glucose and 3-O-MG are reabsorbed from bile after entry at the hepatocyte, accounting for their low bile-plasma ratio. The biliary glucose transport process may be described by Michaelis-Menten kinetics and is analogous to recently defined kinetics for renal tubular reabsorption of glucose. These studies provide evidence that certain products of bile secretion may undergo a "biliohepatic" circulation.
Points from letters: Removal of impacted rectal foreign body with obstetric forceps
Authors: H G Penman
Journal: BMJ (1976)

indicates that consultants in teaching hospitals are on average of higher quality than those in peripheral hospitals and that similar considerations apply respectively to those working in the South and the North of England and also to physicians and surgeons as opposed to geriatricians and psychiatrists.If Drs Bruggen and Bourne do not believe this they should say why.There are, of course, people who believe that merit should not be financially rewarded as the work involved is cleaner and more interesting than unskilled work.There are also people who believe that it is impossible to assess merit and it would appear from the Points from LettersClinical or administrative postal addresses ?
Public health agency needed for Britain
Authors: J. Wise
Journal: BMJ (1997)

Leading figures in health and public policy have called on the government to set up a dedicated public health agency to tackle heart disease in Britain. The agency would assess the health impact of all government policies–from transport to social services–and link national policies with local community health initiatives to ensure a fully integrated approach.

The National Heart Forum said that, although mortality from heart disease had fallen by a third since the 1970s, the reduction in death rates in Britain was not as great as in other Western countries, such as the United States and Australia, where there has been a more vigorous national commitment to tackling …
Diagnosis and management of irritable bowel syndrome in adults in primary care: summary of NICE guidance
Authors: J Dalrymple, I Bullock
Journal: BMJ (2008)

Irritable bowel syndrome (IBS) is a chronic, relapsing, and often lifelong condition of unknown aetiology,1 often associated with non-colonic symptoms. In clinical practice IBS is often diagnosed by the exclusion of more serious illnesses by unnecessary investigations and inappropriate referral. This article summarises the most recent guidance on IBS from the National Institute for Health and Clinical Excellence (NICE); the guidelines cover the diagnosis and management of the syndrome, reflecting the complete patient journey from presentation to positive diagnosis and management.2 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the guideline development group's opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Assessment
Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man.
Authors: N Nurjhan, A Bucci, G Perriello, M Stumvoll, G Dailey, D M Bier, I Toft, T G Jenssen, J E Gerich
Journal: Journal of Clinical Investigation (1995)

To compare glutamine and alanine as gluconeogenic precursors, we simultaneously measured their systemic turnovers, clearances, and incorporation into plasma glucose, their skeletal muscle uptake and release, and the proportion of their appearance in plasma directly due to their release from protein in postabsorptive normal volunteers. We infused the volunteers with [U-14C] glutamine, [3-13C] alanine, [2H5] phenylalanine, and [6-3H] glucose to isotopic steady state and used the forearm balance technique. We found that glutamine appearance in plasma exceeded that of alanine (5.76 +/- 0.26 vs. 4.40 +/- 0.33 mumol.kg-1.min-1, P < 0.001), while alanine clearance exceeded glutamine clearance (14.7 +/- 1.3 vs. 9.3 +/- 0.8 ml.kg-1.min-1, P < 0.001). Glutamine appearance in plasma directly due to its release from protein was more than double that of alanine (2.45 +/- 0.25 vs. 1.16 +/- 0.12 mumol.kg-1.min-1, P < 0.001). Although overall carbon transfer to glucose from glutamine and alanine was comparable (3.53 +/- 0.24 vs 3.47 +/- 0.32 atoms.kg-1.min-1), nearly twice as much glucose carbon came from protein derived glutamine than alanine (1.48 +/- 0.15 vs 0.88 +/- 0.09 atoms.kg-1.min-1, P < 0.01). Finally, forearm muscle released more glutamine than alanine (0.88 +/- 0.05 vs 0.48 +/- 0.05 mumol.100 ml-1.min-1, P < 0.01). We conclude that in postabsorptive humans glutamine is quantitatively more important than alanine for transporting protein-derived carbon through plasma and adding these carbons to the glucose pool.
The clinical course of patients with IgG4-related kidney disease
Authors: Takako Saeki, Mitsuhiro Kawano, Ichiro Mizushima, Motohisa Yamamoto, Yoko Wada, Hitoshi Nakashima, Noriyuki Homma, Yutaka Tsubata, Hiroki Takahashi, Tomoyuki Ito, Hajime Yamazaki, Takao Saito, Ichiei Narita
Journal: Kidney International (2013)
Key players agree to share viruses and vaccines to expedite response to future pandemic influenza
Authors: J. Zarocostas
Journal: BMJ (2011)

Influenza virus samples will be shared worldwide through the World Health Organization system in exchange for a fairer distribution of the benefits, including vaccines to poorer countries, under a new global accord to improve pandemic preparedness agreed in Geneva on 16 April.

Margaret Chan, WHO’s director general called the agreement “a very significant victory for public health.”

Bente Angell-Hansen, Norway’s ambassador who co-chaired the WHO sponsored talks with Mexico’s ambassador, told the BMJ “The world needed an improved system in this area.”

The pandemic influenza preparedness framework includes binding legal regimes for WHO, national influenza laboratories around the world, and industry partners in rich and poor countries to boost …
GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling
Authors: Emira Ayroldi, Ornella Zollo, Alessandra Bastianelli, Cristina Marchetti, Massimiliano Agostini, Rosa Di Virgilio, Carlo Riccardi
Journal: Journal of Clinical Investigation (2007)

Tsc22d3 coding for glucocorticoid-induced leucine zipper (GILZ) was initially identified as a dexamethasone-responsive gene involved in the control of T lymphocyte activation and apoptosis. However, the physiological role of this molecule and its function in the biological activity of glucocorticoids (GCs) has not been clarified. Here, we demonstrate that GILZ interacts directly with Ras in vitro and in vivo as shown by GILZ and Ras coimmunoprecipitation and colocalization upon PMA activation in primary mouse spleen T lymphocytes and thymus cells. The analysis of GILZ mutants showed that they bound Ras through the tuberous sclerosis complex box (TSC) and, depending on the Ras activation level, formed a trimeric complex with Ras and Raf, which we previously identified as a GILZ binder. As a consequence of these interactions, GILZ diminished the activation of Ras and Raf downstream targets including ERK1/2, AKT/PKB serine/threonine kinase, and retinoblastoma (Rb) phosphorylation and cyclin D1 expression, leading to inhibition of Ras- and Raf-dependent cell proliferation and Ras-induced NIH-3T3 transformation. GILZ silencing resulted in an increase in concanavalin A-induced T cell proliferation and, most notably, inhibition of dexamethasone antiproliferative effects. Together, these findings indicate that GILZ serves as a negative regulator of Ras- and Raf-induced proliferation and is an important mediator of the antiproliferative effect of GCs.
Dispersion of refractoriness in normal and ischaemic canine ventricle: effects of sympathetic stimulation
Authors: T. Opthof, R. Coronel, J. T Vermeulen, H. J Verberne, F. J L van Capelle, M. J Janse
Journal: Cardiovascular Research (1993)

Dispersion in refractoriness is considered a major factor in induction and persistence of cardiac arrhythmias. The sympathetic nervous system is known to modulate refractoriness. An index of refractoriness has therefore been assessed in normal and ischaemic myocardium simultaneously at multiple sites, with and without sympathetic stimulation.In six dogs on total cardiopulmonary bypass the average interval between local activations was measured during artificially induced ventricular fibrillation from extracellular electrograms simultaneously recorded from 32 ventricular sites. These local ventricular fibrillation intervals may be used as an index of local refractoriness.During regional ischaemia, ventricular fibrillation intervals of ischaemic sites could prolong by up to 60% after 3 min following coronary occlusion. Left stellate ganglion stimulation during ischaemia produced either no response or prolonged the ventricular fibrillation intervals even further at ischaemic sites, whereas ventricular fibrillation intervals at non-ischaemic sites shortened. Dispersion in refractoriness across the ischaemic border increased by 14-59% in individual hearts following sympathetic stimulation during acute, regional ischaemia.Due to opposite effects on normal and ischaemic myocardium, sympathetic stimulation increases the difference in refractoriness over the ischaemic border. This may enhance the chance for regional conduction block and the propensity to re-entrant arrhythmias.
Bone-scintigraphic examinations in patients treated with retinoids: a prospective study
Authors: L. TOROK, L. GALUSKA, M. KASA, L. KADAR
Journal: British Journal of Dermatology (1989)

Possible early side-effects of retinoid treatment on bones were studied with the aid of bone-scintigraphy. Isotretinoin treatment (1.0 mg/kg daily for 4 months) was given to 18 patients with acne. Fifteen patients with psoriasis received etretinate treatment (0.7-1.0 mg/kg/day) for 4 months. In the group treated with isotretinoin, pathological uptake of radiolabel was found in three cases, while in the group treated with etretinate, no bone changes attributable to treatment were found. During isotretinoin treatment, a decrease in growth-plate activity was observed. Bone-scintigraphy is considered to be a suitable method for early screening for bone changes occurring in retinoid treatment.
Adverse consequences arising from misdiagnosis of food allergy.
Authors: D. A. Robertson, R. C. Ayres, C. L. Smith, R. Wright
Journal: BMJ (1988)

Triazolam, which is widely prescribed as a hypnotic, is considered to be safe even in overdose.In elderly patients, however, overdose may be fatal, particularly in patients taking concomitant drug treatment or with serious disease. Case reportsCase I-A 76 year old woman with bone pain from osteomalacia due to renal tubular acidosis had been treated with alfacalcidol, calcium supplements, sodium bicarbonate, and dihydrocodeine; she was receiving triazolam 0-25 mg as a hypnotic.'She was found dead with a note indicating her intention to take her life.Her bottle of triazolam tablets was empty, but she had not taken an overdose of the other drugs.Necropsy showed early pneumonia and chronic bowel obstruction; these lesions were considered to be capable of having caused her death.In view of the suicide note samples were referred for toxicological analysis.This showed a blood triazolam concentration of 47 nmol/l, which is substantially above mean peak therapeutic concentrations.`3The equivalent of at least five tablets was found in the stomach.Dihydrocodeine was found in therapeutic concentration; analysis for
PULMONARY TUBERCULOSIS MASQUERADING AS LARYNGITIS
Authors: JOSEPH C. DONNELLY
Journal: JAMA (1942)

My purpose in this paper is to call attention to or promote wider recognition of the fact that pulmonary tuberculosis may first be manifested by laryngeal symptoms. It is not to be construed that the tuberculous process originates in the larynx, because it is axiomatic today that laryngeal tuberculosis is always secondary to a pulmonary focus. Unlike hemoptysis, which is so alarming to the patient and significant to the physician, the presence of either chronic hoarseness or sore throat is frequently disregarded as a serious warning by both patient and consultant.  While the incidence of laryngeal symptoms antedating pulmonary or systemic signs is small, nevertheless a review of the history and laryngeal examination of 1,800 patients observed at the White Haven Sanatorium revealed that the cart came before the horse in 26 of these patients, or a frequency approximating 1.5 per cent. It would have been instructive to know the
477. Replication Deficiency: The Safety Record of a New Sendai Virus Vector Generation
Authors: Sascha Bossow, Sabine Schlecht, Marian Wiegand, Wolfgang J. Neubert
Journal: Molecular Therapy (2006)

Sendai virus (SeV) is a non-segmented negative-strand RNA virus belonging to the family Paramyxoviridae. Current development as a cytoplasmic RNA vector and pre-clinical testing indicate SeV to be a promising gene transfer system. However, future applications require the detailed characterization of safety issues for every vector system and vector generation. To prevent an unrestrained spread of vector sequences, deletions of non-essential functions in the vector backbone are necessary, thereby maintaining efficient vector- mediated transgene expression. We and others have developed recently several non-transmissible SeV vectors devoid of the viral envelope protein genes. As a new safety approach, we created SeV deletion mutants with a modified polymerase complex incapable of genome replication but showing a primary transcription of the input genome template. Recombinant SeV mutants with an altered P (non-catalytic phosphoprotein polymerase cofactor) gene were generated by either 1) deleting the entire P ORF (ΔP) or by replacing the P ORF with the coding sequences of the non-structural proteins 2) V (ΔP-V) and 3) W (ΔP-W). All ΔP variants could replicate and produce progeny particles in a helper cell line that constitutively expresses the P protein, whereas no progeny virus was released from infected host cells that did not provide P protein in trans. The P ORF-deleted recombinants performed only a weak primary RNA transcription by the virion-associated polymerase in infected host cells. In terms of optimizing the gene expression of a replication-deficient SeV vector, a fourth variant was created by deleting the N-terminal76 codons of the P ORF (PΔ2-77). SeV PΔ2-77 could be amplified on a helper cell line leading to titers only twice lower than wild-type SeV, and it was replication-deficient after infection of non-helper host cells. Moreover, SeV PΔ2-77 is capable of a secondary transcription due to de novo synthesis of truncated P protein, resulting in an only 10-fold reduced expression level compared to wild-type SeV. Over a period of 12 days after infection, a constant gene expression could be detected. These results confirm that the deletion of the first 76 amino acids of the P protein is sufficient to abrogate SeV genome replication. Uncoupling viral transcription and genome replication using the truncated P protein PΔ2-77 may render SeV a potent and safe replication-deficient viral vector with maintained gene expression.
Pre-transplant imatinib-based therapy improves the outcome of allogeneic hematopoietic stem cell transplantation for BCR–ABL-positive acute lymphoblastic leukemia
Authors: S Mizuta, K Matsuo, F Yagasaki, T Yujiri, Y Hatta, Y Kimura, Y Ueda, H Kanamori, N Usui, H Akiyama, Y Miyazaki, S Ohtake, Y Atsuta, H Sakamaki, K Kawa, Y Morishima, K Ohnishi, T Naoe, R Ohno
Journal: Leukemia (2010)
Abstract 4137: Verification of antitumor effect of γ-secretase-inhibitor and radiotherapy
Authors: Hidenori Mizugaki, Jun Konishi, Junko Kikuchi, Eiki Kikuchi, Naofumi Shinagawa, Satoshi Oizumi, Masaharu Nishimura
Journal: Cancer Research (2010)

Abstract [Background and Aim] Notch3 is a member of the Notch signaling pathway, which plays an important role in cancer development. We have already demonstrated that Notch3 is over-expressed in approximately 40% of lung cancer tumors and that inhibition of the Notch3 pathway by γ-secretase-inhibitor (GSI) induces apoptosis and suppresses tumor growth in lung cancer. Although a previous report has shown that radiation enhanced Notch1 expression in breast cancer, little is known about the relationship between radiation and Notch pathway. In this study, we attempt to elucidate the combined effect of GSI and radiotherapy in lung cancer. [Results] We used two Notch3-expressing lung cancer cell lines (HCC2429 and H460). In a MTT proliferation assay and clonogenic assay, combination of GSI and radiation suppressed the growth of lung cancer cells and colony formations compared to GSI or radiation alone. We also showed that GSI down-regulates Notch3 expression in a dose dependent manner, and radiation up-regulates Notch expression and downstream Notch target gene, Hey-1. Notch up-regulation by radiation is down-regulated by the combination. Combination of GSI and radiation reduced p-Bcl2, Bcl-XL and p-Erk compared to GSI or radiation alone, whereas no effect on p-Akt level was seen.[Conclusion] Our results suggest that combination of GSI and radiation may be clinical potential strategy in the treatment of patients with lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4137.
How Physicians Can Change the Future of Health Care
Authors: Michael E. Porter, Elizabeth Olmsted Teisberg
Journal: JAMA (2007)

Today's preoccupation with cost shifting and cost reduction undermines physicians and patients. Instead, health care reform must focus on improving health and health care value for patients. We propose a strategy for reform that is market based but physician led. Physician leadership is essential. Improving the value of health care is something only medical teams can do. The right kind of competition--competition to improve results--will drive dramatic improvement. With such positive-sum competition, patients will receive better care, physicians will be rewarded for excellence, and costs will be contained. Physicians can lead this change and return the practice of medicine to its appropriate focus: enabling health and effective care. Three principles should guide this change: (1) the goal is value for patients, (2) medical practice should be organized around medical conditions and care cycles, and (3) results--risk-adjusted outcomes and costs--must be measured. Following these principles, professional satisfaction will increase and current pressures on physicians will decrease. If physicians fail to lead these changes, they will inevitably face ever-increasing administrative control of medicine. Improving health and health care value for patients is the only real solution. Value-based competition on results provides a path for reform that recognizes the role of health professionals at the heart of the system.
Management of people who have been raped
Authors: J. Wilken
Journal: BMJ (2003)

Rape is common but under-reported, with an estimated lifetime risk of up to one in four for women.1 Definitions vary between countries; in England and Wales the term refers to non-consensual vaginal or anal penetration by a penis, of a woman or a man. Serious sequelae include psychological problems, infection, and unwanted pregnancy. People who have been raped may present, immediately or later, to general practitioners or other clinicians, not all of whom may be familiar with such situations. Here we outline the care of people who present after sexual assault; we use the relatively neutral term clients, as suggested elsewhere.2

Optimal management depends on the client's wishes and needs, time since assault, and whether involvement of the police is requested. Meticulous medical notes are essential even if involvement of the police is declined initially, as reports may be required later for legal processes or compensation. Immediate considerations include safety, management of injuries, forensic examination, and emergency contraception. In situations of domestic violence or perpetrator's physical proximity a …
Laboratory methods of assessing hearing loss.
Authors: A R Møller
Journal: Environmental Health Perspectives (1982)

Methods for assessing hearing loss in human loss in human and in animal are reviewed with special reference to the use of brainstem auditory evoked potentials (BSEP). The technique of recording and digital filtering of BSEP is described and compared with the results obtained by use of traditional analog filtering. The use of electrophysiological methods in assessing threshold shifts in studies of the effect of noise exposure on hearing in experimental animals is described for examples of results obtained in rats.