tbuckley/cabot-search huggingface dataset:
Plasma cholesterol, coronary heart disease, and cancer: Authors' reply
Authors: C G Isles, D J Hole, C R Gillis, V M Hawthorne, A F Lever
Journal: BMJ (1989)

associations between a putative risk factor and multifactorial diseases, there are at least two points worth comment.The authors discount the possibility that premature death from ischaemic heart disease accounted for the negative association between cholesterol concentrations and cancer, stating that the average age at death from each cause was similar for each concentration of plasma cholesterol.Thus it seems that the ages at death from cancer in their population followed the same pattern as the ages at death from ischaemic heart disease when grouped according to the plasma cholesterol concentration: those with low cholesterol concentrations lived longer before developing cancer, a curious finding if the negative association is true.Also, the direct relation between smoking and cancer should be addressed, particularly in view of the predominance of lung cancer.It is important to know whether those developing cancer were more likely to be smokers and, if so, whether they had high' or low plasma cholesterol concentrations; these concentrations if compared with those from smokers without cancer, matched for other risk factors, age, and sex, might show whether a low plasma cholesterol concentration is an additional risk factor.No evidence is given that the association is causal, and it should not affect the advice on health matters offered by doctors, especially to patients with other risk factors for cardiovascular disease.Public awareness will make the work of those attempting to reduce the incidence of ischaemic heart disease in "at risk" groups even harder.
Prefrontal Lobotomy in the Chronic Depressive States of Old Age
Authors: Abraham Myerson, Paul G. Myerson
Journal: New England Journal of Medicine (1947)

THE operation known as prefrontal lobotomy was first performed by Moniz1 in 1936. Since that time, the procedure has been widely employed in many types of mental illness in which the course of the disease has been prolonged and the outlook desperate. The operation consists of the cutting of a part of the fibers between the thalamus and prefrontal lobes.2 , 3 The rationale has been to disassociate, by surgical means, pathologic thinking from its emotional reverberation. This, of course, is a vast oversimplification of an extremely complex psychologic and neurophysiologic event. The results, when successful, have relieved patients of overwhelming anxiety, . . .
Current Metabolic-Genetic Interrelationship in Human Atherosclerosis
Authors: PETER T. KUO
Journal: Annals of Internal Medicine (1968)

A few simple laboratory methods have been suggested for phenotyping of clinical hyperlipidemias. Proper classification of plasma lipid abnormalities would provide the physician with an insight into the basic metabolic disorder in hyperlipidemia and atherosclerosis. One of the more important developments has been the demonstration that increased sensitivity to dietary carbohydrate as manifested in hyperpre-beta-lipoproteinemia (rich in both cholesterol and triglycerides) may be quite widespread among apparently healthy persons while the process is exaggerated in the majority of atherosclerotic patients. Evidence is accumulating rapidly to support the concept for disorder in carbohydrate metabolism as the major etiological factor in human atherosclerosis. Although hyperlipidemia is frequently encountered in diabetes mellitus, patients with abnormal sensitivity to carbohydrate are characterized primarily by increased endogenous lipogenesis. Preliminary data suggest that this disorder is initiated and sustained by an abnormal insulin mechanism with high plasma insulin-like activities, but normal blood sugar response to carbohydrate meals. The current status of several promising chemotherapeutic agents is reviewed. Their effects upon the control of this special form of disorder in carbohydrate metabolism are being actively investigated. Tentatively, a sugar-restrictive 125-g carbohydrate diet seems to be useful for the control of the metabolic disorder.
Alternans of Atrial Action Potentials During Atrial Flutter as a Precursor to Atrial Fibrillation
Authors: Sanjiv M. Narayan, Frank Bode, Pamela L. Karasik, Michael R. Franz
Journal: Circulation (2002)

The mechanisms underlying the transition of typical atrial flutter (Afl) to fibrillation (AF) remain unclear. We set out to test the hypothesis that Afl disorganizes to AF via alternans of atrial action potentials.In 38 patients with Afl, monophasic action potentials (MAPs) were recorded at the isthmus and either high or low right atrium (HRA, LRA) during overdrive pacing to 160 ms or to the initiation of AF, whichever came first. MAP duration measured at 90% repolarization was longer at the isthmus in all patients, and failed to shorten with rate, compared with the HRA (n=38) or LRA (n=5). In 20 patients who developed AF, progressive pacing first caused alternans of isthmus MAP duration and amplitude at mean cycle length of 219+/-45 ms, followed by AF at a mean onset cycle length of 184+/-38 ms. Subsets of this group showed spontaneous action potential duration alternans at the isthmus (11 of 20 patients) and 2:1 isthmus conduction block immediately preceding AF (4 of 20 patients). In the 18 patients who did not develop AF, MAP alternans was less common (9 of 18 patients; P<0.0003), and occurred only at faster pacing (cycle length=169+/-25 ms; P<0.05).In patients with typical Afl, action potential duration rate maladaptation at the isthmus may lead to action potential duration alternans and conduction block preceding the transition to AF. These isthmus characteristics may enable the spontaneous initiation of AF through wavefront fractionation and may explain the benefits of isthmus ablation in preventing AF recurrence.
Significance of the Changes in the Respiratory System Pressure–Volume Curve during Acute Lung Injury in Rats
Authors: LAURENT MARTIN-LEFÈVRE, JEAN-DAMIEN RICARD, ERIC ROUPIE, DIDIER DREYFUSS, GEORGES SAUMON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The hypothesis that the changes in the respiratory system pressure– volume (PV) curve during pulmonary edema mainly reflect distal airway obstruction was investigated in rats. Normal rats had a well-defined upper inflection point (UIP) at low airway pressure. Airway occlusion by liquid instillation decreased compliance (Crs) and the volume (Vuip) of the UIP, and increased end-inspiratory pressure. The same changes were observed during the progression of edema produced by high volume ventilation (HV). Changes in Vuip and in Crs produced by HV were correlated with edema severity in normal rats or rats with lungs preinjured with α -naphthylthiourea. Vuip and Crs changes were proportional, reflecting compression of the PV curve on the volume axis and suggesting reduction of the amount of ventilatable lung at low airway pressure. In keeping with this explanation, the lower Vuip and Crs were before HV, the more severe HV-induced edema was in α -naphthylthiourea-injected rats. When edema was profuse, PV curves displayed a marked lower inflection point (LIP), the UIP at low pressure disappeared but another was seen at high volume above the LIP, and the correlation between Vuip changes and edema severity was lost. These observations may have clinical relevance in the context of the “open lung” strategy.Keywords: ventilator-induced lung injury; respiratory mechanics; acute respiratory distress syndrome
Delayed G‐CSF stimulation after PBSCT does not seem to modify the biological parameters of bone marrow recovery
Authors: Jean-Christophe Ianotto, Adrian Tempescul, Pascal Delepine, Gaelle Guillerm, Elisabeth Hardy, Jean-Richard Eveillard, Christian Berthou
Journal: American Journal of Hematology (2011)

There are currently no recommendations indicating when stimulation should begin after autologous peripheral blood stem cell transplantation (PBSCT). We compared the outcome following between two treatment groups, in which daily granulocyte colony stimulating factor (G-CSF) administration began on either the fifth or the eighth day after PBSCT in lymphoma and myeloma patients. We studied eight clinical parameters: number of G-CSF injections, number of days of hospitalization, of red blood cell or platelet transfusions; days when body temperature exceeds 38°C; days of parenteral nutrition; weight loss and hospitalization costs. We studied also four biological parameters: number of CD34+ cells, days with leucocytes less than 1 × 10(9) /L, days with hemoglobin less than 90 g/L or with less than 50 × 10(9) /L of platelets. There were no statistical significant differences between the study arms. It seems that delayed stimulation by G-CSF after PBSCT is safety and does not seem to modify bone marrow recovery timing.
Chronic diarrhoea with thickening of the colonic wall
Authors: K Kishimoto, A Hokama, S Irei, H Aoyama, R Tomiyama, T Hirata, F Kinjo, J Fujita, M Sakiyama
Journal: Gut (2006)

A 36-year-old woman who had a seven-year medical history of type 1 diabetes mellitus presented with diarrhoea of 1-month duration. She denied abdominal pain …
Effect of the Transformation of the Veterans Affairs Health Care System on the Quality of Care
Authors: Ashish K. Jha, Jonathan B. Perlin, Kenneth W. Kizer, R. Adams Dudley
Journal: New England Journal of Medicine (2003)

In the mid-1990s, the Department of Veterans Affairs (VA) health care system initiated a systemwide reengineering to, among other things, improve its quality of care. We sought to determine the subsequent change in the quality of health care and to compare the quality with that of the Medicare fee-for-service program.Using data from an ongoing performance-evaluation program in the VA, we evaluated the quality of preventive, acute, and chronic care. We assessed the change in quality-of-care indicators from 1994 (before reengineering) through 2000 and compared the quality of care with that afforded by the Medicare fee-for-service system, using the same indicators of quality.In fiscal year 2000, throughout the VA system, the percentage of patients receiving appropriate care was 90 percent or greater for 9 of 17 quality-of-care indicators and exceeded 70 percent for 13 of 17 indicators. There were statistically significant improvements in quality from 1994-1995 through 2000 for all nine indicators that were collected in all years. As compared with the Medicare fee-for-service program, the VA performed significantly better on all 11 similar quality indicators for the period from 1997 through 1999. In 2000, the VA outperformed Medicare on 12 of 13 indicators.The quality of care in the VA health care system substantially improved after the implementation of a systemwide reengineering and, during the period from 1997 through 2000, was significantly better than that in the Medicare fee-for-service program. These data suggest that the quality-improvement initiatives adopted by the VA in the mid-1990s were effective.
The Church of Saint Séverin
Authors: Harold A. Burnham
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The interesting description (238:2692, 1977) on the<i>Church of Saint Séverin</i>on the cover of the June 20, 1977, issue ofThe Journalomitted part of the medical history associated with this remarkable edifice.<sup>1</sup>The galleries referred to in the cover article are the present day remains of a charnel house that surrounded a burial ground. A charnel house is a structure attached to a church, whereas an ossuary is not necessarily located on church grounds. The galleries of Saint Séverin Church look much as they did during the 15th century. As the burial ground became congested, the charnel house walls, essentially hollow spaces, were filled with the bones of the dead taken from their graves. According to the known history of Saint Séverin Church, it was on this burial ground that the first recorded operation for gallstones was performed in France. In 1474 a surgeon
Allergic Complications of Meningococcal Disease I--Clinical Aspects
Authors: H. C. Whittle, M. T. Abdullahi, F. A. Fakunle, B. M. Greenwood, A. D. M. Bryceson, E. H. O. Parry, J. L. Turk
Journal: BMJ (1973)

Out of 717 patients with meningococcal disease 53 showed one or more of the three allergic complications: 47 (6.6%) developed arthritis, 12 (1.7%) developed cutaneous vasculitis, and 6 developed episcleritis. These complications, which were often multiple, occurred six to nine days after the beginning of the illness and three to six days after the start of successful antibiotic therapy. Those patients with severe systemic disease were prone to the complications.Histological and bacteriological study of the arthritis and vasculitis showed that these lesions were probably not due to persisting infection and suggested that they might be due to immune complex disease.
Gorhamʼs Syndrome
Authors: BRIAN J. IGEL, HEMENDRA SHAH, MICHAEL R. WILLIAMSON, JAMES J. SELL
Journal: Clinical Nuclear Medicine (1994)

The authors present a case of Gorham's syndrome involving the mandible in a 52-year-old man demonstrated by multiple imaging modalities. Gorham's Syndrome (disappearing bone disease, massive osteolysis) is a rare idiopathic disorder of bone characterized radiographically by progressive bony resorption. The process is usually monostotic in the initial phase with involvement of adjacent bones by direct spread across joint spaces. The clinical course is unpredictable with spontaneous arrest of the osteolysis being common.
Unlicensed and off label drug use in paediatric wards: prospective study
Authors: S. Turner, A. Longworth, A. J Nunn, I. Choonara
Journal: BMJ (1998)

To determine the extent of use in children in hospital of drugs that are not specifically licensed for use in children (unlicensed) and of drugs that are used outside the terms of their product licence that apply to indication, age, dose, or route of administration (off label).Prospective study of drugs administered on paediatric medical and surgical wards for 13 weeks.Regional children's hospital.Paediatric inpatients in medical and surgical wards.Comparison of the use of each drug with its product licence to determine whether the drug was used in an unlicensed or off label manner.2013 courses of drugs were administered to 609 paediatric patients in 707 admissions. 506 (25%) of the drug courses (prescriptions) were either unlicensed (139) or off label (367) uses. In 256 (36%) of the 707 admissions patients received one or more courses of an unlicensed or off label treatment in hospital.Use of drugs in an off label or unlicensed manner to treat children is widespread. Drugs are more likely to be used in an off label manner than in an unlicensed manner.
FUNCTIONAL HETEROGENEITY OF MURINE LYMPHOID CELLS
Authors: John D. Stobo, Alan S. Rosenthal, William E. Paul
Journal: The Journal of Experimental Medicine (1973)

An appreciable percent (3-14%) of the lymphocyte-like cells of the mouse spleen lack both the theta-isoantigen and sufficient surface immunoglobulin to be detected by conventional immunofluorescence or autoradiographic procedures. These theta(-),Ig(-) cells are increased in frequency after treatment of mice with antithymocyte serum or in mice that have been thymectomized, irradiated (850 R), and reconstituted with bone marrow cells. Moreover, in chimeric C57BL/6 mice in which the T cells are derived from (BALB/c x C57BL/6)F(1) donors, theta(-),Ig(-) cells also lack BALB/c histocompatibility antigens. These experiments indicate that theta(-),Ig(-) cells are not theta(-) T lymphocytes. Removal of complement receptor lymphocytes from spleen cell populations increases the frequency of theta(-),Ig(-) cells, indicating that such cells lack the complement receptor. Partially purified populations of theta(-),Ig(-) cells have been obtained by cytolysis by anti-theta- and anti-kappa-antibody and complement and by density gradient ultracentrifugation. These cells closely resemble lymphocytes in morphology. The only exceptional feature is the existence of prominent nucleoli. The theta(-),Ig(-) cells lack hemoglobin and endogenous peroxidases, are not actively phagocytic, and do not adhere to glass. This suggests they are not of the erythroid, myeloid, or monocytoid lines. [(3)H]Thymidine labeling studies indicate that theta(-),Ig(-) cells are members of a relatively slowly dividing cell pool. Whether theta(-),Ig(-) cells are members of the "classical" B lymphocyte line or belong to another, as yet undescribed, lineage is not yet certain.
Selective increase in plasma luteinising hormone concentrations in drug free young men with mania.
Authors: L J Whalley, J E Christie, J Bennie, H Dick, I M Blackburn, D Blackwood, G Sanchez Watts, G Fink
Journal: BMJ (1985)

The hypothalamic-pituitary-gonadal system was investigated in drug free young men with either mania or acute schizophrenia and in age matched controls by measuring, at frequent intervals during a 17 hour "neuroendocrine day," plasma concentrations of luteinising hormone (LH), follicle stimulating hormone, prolactin, testosterone, sex hormone binding globulin (SHBG), and cortisol. Plasma LH in mania was significantly increased compared with the control value at all time periods and increased in the morning and evening samples compared with values in the schizophrenic patients. Plasma prolactin and cortisol concentrations were significantly greater in mania and schizophrenia compared with control values at several times during the day, but there were no significant between group differences in plasma testosterone or SHBG. These results show that in young men with mania there is a major disturbance in the central mechanisms that control the release of LH, the control of prolactin and cortisol secretion is abnormal in mania and acute schizophrenia, and plasma LH concentrations may provide a useful hormonal diagnostic test for mania.
Abstract B29: TGF-β2 induction in head and neck squamous cell carcinoma cell lines upon treatment with tyrosine kinase inhibitors as a mechanism of acquired resistance
Authors: Emily K. Kleczko, Lydia Heasley, Lynn E. Heasley
Journal: Clinical Cancer Research (2012)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide, with 600,000 new diagnoses each year. Due to the fact that over 90% of HNSCC tumors overexpress the epidermal growth factor receptor (EGFR), molecularly targeted therapy against EGFR was approved to treat HNSCC. However, the 5-year survival rate for HNSCC patients, largely unchanged over the past several decades, remains at a dismal 40–50%, and the use of cetixumab, an EGFR-specific monoclonal antibody, has only had a marginal effect on overall survival. Likewise, the use of tyrosine kinase inhibitors (TKIs) that target EGFR has not resulted in an increased survival among HNSCC patients. The modest effect of these drugs on overall survival in HNSCC patients may be a result of tumors becoming resistant to treatment in responding patients. Acquired drug resistance has become a significant limitation to the efficacy of targeted therapeutics. Previously, our lab has identified fibroblast growth factor 2 (FGF2) and its receptor (FGFR) as being involved in an autocrine loop in gefitinib-insensitive cell lines, indicating that the FGFR pathway plays an important role in HNSCC as well. However, targeting FGFR with TKIs will almost undoubtedly lead to drug resistance in these FGFR-dependent cell lines, just as it does when targeting EGFR. To identify pathways important in acquired resistance to TKIs, our lab performed an Affymetrix GeneChip screen in which the cell lines UMSCC25, 584-A2, and Ca9-22 were treated for 4 days with 0.3μM AZ8010, a TKI selective for FGFRs, and/or 0.1μM gefitinib, an EGFR-selective TKI. TGF-β2 was consistently upregulated after treatment with TKIs that inhibited the dominant growth pathway in the HNSCC cell lines. Both ELISA and qRT-PCR confirmed this induction of TGF-β2 in these three cell lines. Treatment with a TGF-β2 neutralizing antibody and with small-molecule TGF-β receptor inhibitors provided additive reduction of growth in response to TKIs. Additionally, silencing TGF-β2 with shRNA in the cell line UMSCC25 leads to decreased clonogenic growth in combination with TKIs compared to a non-silencing control (NSC). Moreover, we found that an induction of NF-kB activity occurs in response to treatment with TKIs, and this induction is mitigated by the addition of a TGF-β2 neutralizing antibody. Furthermore, the cell lines UMSCC25 and UMSCC22A were chronically adapted to gefitinib over the course of several months, and we have observed a stable, prolonged increase in TGF-β2 mRNA expression in the resistant lines compared to the DMSO control lines. Taken together, this data suggests that TGF-β2 induction may provide a novel mechanism of acquired resistance to TKIs, and possibly contributes to oncogene switching programs in HNSCC.
Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia
Authors: Jerome Tamburini, Alexa S. Green, Valerie Bardet, Nicolas Chapuis, Sophie Park, Lise Willems, Madalina Uzunov, Norbert Ifrah, François Dreyfus, Catherine Lacombe, Patrick Mayeux, Didier Bouscary
Journal: Blood (2009)
[25] IDENTIFICATION OF HLA-DR3 RESTRICTED CD4 T-CELL EPITOPES ON SOLUBLE LIVER ANTIGEN IN AUTOIMMUNE HEPATITIS TYPE 1
Authors: F. Meda, P. Wang, M.S. Longhi, D.P. Bogdanos, G. Mieli-Vergani, D. Vergani, Y. Ma
Journal: Journal of Hepatology (2007)
The South Asian Earthquake Six Months Later — An Ongoing Crisis
Authors: Richard J. Brennan, Ronald J. Waldman
Journal: New England Journal of Medicine (2006)

The magnitude 7.6 earthquake that struck northern Pakistan and India on October 8, was the world's third-deadliest natural disaster of the past 25 years. Today only 66 percent of the “flash appeal” issued by the United Nations has been funded. Drs. Richard Brennan and Ronald Waldman write that important needs remain unmet.
Immunoglobulin VH genes are transcribed by T cells in association with a new 5' exon.
Authors: R Baer, A Forster, I Lavenir, T H Rabbitts
Journal: The Journal of Experimental Medicine (1988)

We previously detected mRNAs in a number of human T cell lines with a probe from within the Ig VH gene locus. We now show these mRNAs consist of Ig VH genes expressed in T cells. In one human T cell line, two RNA species have been studied and found to come from transcripts of unrearranged VH segments in which the leader exon, normally associated with VH transcripts in B cells, is replaced by a novel 5' exon (ET) not encoding a hydrophobic leader peptide. In genomic DNA, this new ET exon is adjacent to a pseudo-VH gene that has not been observed in mature mRNA. This implies that RNA splicing controls association of the new exon with the expressed VH segments. Hence, VH transcription does indeed occur in T cells, but is qualitatively different from that in B cells.