tbuckley/cabot-search huggingface dataset:
$89m award likely to go to appeal in US
Authors: F B Charatan
Journal: BMJ (1994)

An $89m (pounds sterling 59m) award made by a Californian jury to the family of a woman who died of breast cancer is likely to be contested in the appeal courts, legal experts said last week. The woman, Nelene Fox, was refused insurance cover for bone marrow transplantation on the grounds that it was of unproved value.

Mrs Fox was found to have breast cancer at the age of 38 in 1991. She had bilateral mastectomies and chemotherapy but developed bony metastases. When she sought a bone marrow …
Occurrence of Growth-Hormone Deficiency in Acromegaly as a Result of Pituitary Apoplexy
Authors: Robert S. Rigolosi, Ernest Schwartz, Seymour M. Glick
Journal: New England Journal of Medicine (1968)

HEMORRHAGIC necrosis is a well documented complication of pituitary tumor, thought by some to occur more frequently in eosinophilic adenomas than in chromophobe adenomas,1 and occasionally related to radiotherapy.2 , 3 We have been able to find in the literature endocrinologic evaluations of four acromegalic patients who survived apparent pituitary apoplexy. Two of these patients were observed to have regression of acromegalic signs, associated with improvement of diabetes mellitus in one patient4 and with the development of hypopituitarism in the other.5 In two other acromegalic patients hypopituitarism6 and amelioration of diabetes mellitus7 were observed to develop respectively, but the subsequent course of . . .
ATYPICAL MASTOIDITIS: CASE WITH DEEP ABSCESS IN TEMPORAL FOSSA, BEGINNING AS SUSPECTED PAROTITIS
Authors: Ewald Hermann
Journal: JAMA (1930)

A girl, aged 8 years, with irrelevant history, during the past winter had had occasional attacks of pain in both ears, with more in the left. April 28, she was awakened from sleep about 11 o'clock with sharp pains in the left ear. The family physician saw her the next morning and on the second day the ear spontaneously began discharging freely. A boric acid irrigation was used twice a day, and after five days the discharge stopped. However, the pain continued and all this time there was a variable, fluctuating temperature as high as 102 F. There was no swelling or tenderness over the mastoid. Sodium salicylate and acetylsalicylic acid were prescribed for pain and the control of fever. As soon as the discharge stopped, a swelling was noticed just in front of and on a level with the external auditory canal. This swelling extended anteriorly upward and above
Automatic and triggered impulse initiation in canine subepicardial ventricular muscle cells from border zones of 24-hour transmural infarcts. New mechanisms for malignant cardiac arrhythmias?
Authors: K H Dangman, K P Dresdner, S Zaim
Journal: Circulation (1988)

With standard microelectrode techniques, electrical activity of cells in the epicardial border zones of infarcts in the canine heart were studied. Either automaticity or triggered activity (or both) occurred in each of the 12 preparations studied from 24-hour infarcts. One 24-hour preparation had continuous activity indistinguishable from low-potential (abnormal) automaticity. This automaticity was not effected by flecainide 1-5 mg/l. Two other 24-hour subepicardial muscle preparations also were automatic. However, nine preparations from the subepicardium were not automatic during superfusion with standard Tyrode's solution. Delayed afterdepolarizations (DADs) and triggered activity could be induced in all of these preparations by treatment with catecholamines. The amplitude of these DADs was directly related to the stimulus rate of the train of impulses used to elicit them, and their coupling interval was inversely related to this rate of stimulation. Triggered activity occurred from maximal diastolic potentials of -58 to -88 mV in the 24-hour infarct zone preparations. In seven preparations from 72-96-hour infarct zones, the epicardial muscle cells did not show triggered activity after treatment with catecholamines. In one preparation from a 72-hour infarct, however, 3-5-mV DADs occurred. No DADs or triggered impulses occurred in subepicardial muscle from normal, noninfarcted hearts. Thus, triggered impulses and low-potential automaticity could contribute to arrhythmias occurring in the canine heart 24 hours after coronary ligation.
Spontaneous production of an interleukin 1-like factor by cloned rheumatoid synovial cells in long-term culture.
Authors: M Goto, M Sasano, H Yamanaka, N Miyasaka, N Kamatani, K Inoue, K Nishioka, T Miyamoto
Journal: Journal of Clinical Investigation (1987)

We have cloned adherent synovial cells from rheumatoid synovitis. These can be generally divided into three types, including cells that have the characteristic features of dendritic cells (DCs), macrophagelike cells (MCs) and fibroblastlike cells (FCs), as classified by morphology and immunofluorescent staining. The cloned cells were able to divide and were cultured for up to 11 mo without any significant morphological changes. All the cloned cells were HLA-DR+ after gamma-interferon treatment. Spontaneous production of a factor with interleukin 1 activity by the cloned cells was detected even after long-term culture (the ability, on a per cell basis, being in the following order: DC greater than MC greater than FC). These synovial cells may be important for bony destruction in rheumatoid joints.
Relationship Between Resistance to Insulin-Mediated Glucose Uptake, Urinary Uric Acid Clearance, and Plasma Uric Acid Concentration
Authors: Francesco Facchini
Journal: JAMA (1991)

<h3>Objective.</h3> —To define the relationship, if any, between insulin-mediated glucose disposal and serum uric acid. <h3>Design.</h3> —Cross-sectional study of healthy volunteers. <h3>Setting.—</h3> General Clinical Research Center, Stanford (Calif) University Medical Center. <h3>Participants.</h3> —Thirty-six presumably healthy individuals, nondiabetic, without a history of gout. <h3>Measurements.</h3> —Obesity (overall and regional), plasma glucose and insulin responses to a 75-g oral glucose load, fasting uric acid concentrations, plasma triglyceride and high-density lipoprotein—cholesterol concentrations, systolic and diastolic blood pressure, insulin-mediated glucose disposal, and urinary uric acid clearance. <h3>Results.</h3> —Magnitude of insulin resistance and serum uric acid concentration were significantly related (<i>r</i>=.69;<i>P</i>&lt;.001), and the relationship persisted when differences in age, sex, overall obesity, and abdominal obesity were taken into account (<i>r</i>=.57;<i>P</i>&lt;.001). Insulin resistance was also inversely related to urinary uric acid clearance (<i>r</i>= -.49;<i>P</i>&lt;.002), and, in addition, urinary uric acid clearance was inversely related to serum uric acid concentration (<i>r</i>= -.61;<i>P</i>&lt;.001). <h3>Conclusions.</h3> —Urinary uric acid clearance appears to decrease in proportion to increases in insulin resistance in normal volunteers, leading to an increase in serum uric acid concentration. Thus, it appears that modulation of serum uric concentration by insulin resistance is exerted at the level of the kidney. (<i>JAMA</i>. 1991;266:3008-3011)
Polymerase chain reaction for the diagnosis of viral hepatitis B and C.
Authors: C Brechot
Journal: Gut (1993)

Polymerase chain reaction is a highly sensitive technique for the detection of hepatitis B virus-DNA and hepatitis C virus-RNA in serum, liver tissue, and peripheral mononuclear blood cells. In chronic hepatitis B, it is particularly useful for identification of infectious subjects who are hepatitis B surface antigen positive and anti-hepatitis B e antigen antibody-positive, and for follow up of hepatitis B virus infections in liver transplantation programmes. Polymerase chain reaction detection of hepatitis C virus-RNA in serum may be the only means of confirming acute hepatitis C infection and also of identifying viraemia in the chronic disease, particularly in anti-hepatitis C virus antibody-negative individuals. It can also be used for direct evaluation of mother to child hepatitis C virus transmission. As in hepatitis B, polymerase chain reaction can be used for monitoring reinfection with hepatitis C virus after liver transplant, and has proved invaluable in identification of different hepatitis C virus genotypes. The efficacy of antiviral treatment can also be monitored using polymerase chain reaction. Polymerase chain reaction has thus shown numerous advantages for disease detection and monitoring despite the limitations imposed, for example, by possible contamination problems and semiquantitative evaluations.
Breast screening: time for a rethink?
Authors: M. M. Roberts
Journal: BMJ (1989)

4 Hl Ic A [lI .9i..1 rt.ltIr otIihi e nini rar.LoIndiiii: 1H1 '(d 5(Cooper J1liN Bwnowcr RS, Kit/ RJ.An anal.sisritajior crror', and cquipcinci i/i
Is Volume Related to Outcome in Health Care? A Systematic Review and Methodologic Critique of the Literature
Authors: Ethan A. Halm, Clara Lee, Mark R. Chassin
Journal: Annals of Internal Medicine (2002)

Purpose: To systematically review the methodologic rigor of the research on volume and outcomes and to summarize the magnitude and significance of the association between them. Data Sources: The authors searched MEDLINE from January 1980 to December 2000 for English-language, population-based studies examining the independent relationship between hospital or physician volume and clinical outcomes. Bibliographies were reviewed to identify other articles of interest, and experts were contacted about missing or unpublished studies. Study Selection: Of 272 studies reviewed, 135 met inclusion criteria and covered 27 procedures and clinical conditions. Data Extraction: Two investigators independently reviewed each article, using a standard form to abstract information on key study characteristics and results. Data Synthesis: The methodologic rigor of the primary studies varied. Few studies used clinical data for risk adjustment or examined effects of hospital and physician volume simultaneously. Overall, 71% of all studies of hospital volume and 69% of studies of physician volume reported statistically significant associations between higher volume and better outcomes. The strongest associations were found for AIDS treatment and for surgery on pancreatic cancer, esophageal cancer, abdominal aortic aneurysms, and pediatric cardiac problems (a median of 3.3 to 13 excess deaths per 100 cases were attributed to low volume). Although statistically significant, the volume–outcome relationship for coronary artery bypass surgery, coronary angioplasty, carotid endarterectomy, other cancer surgery, and orthopedic procedures was of much smaller magnitude. Hospital volume–outcome studies that performed risk adjustment by using clinical data were less likely to report significant associations than were studies that adjusted for risk by using administrative data. Conclusions: High volume is associated with better outcomes across a wide range of procedures and conditions, but the magnitude of the association varies greatly. The clinical and policy significance of these findings is complicated by the methodologic shortcomings of many studies. Differences in case mix and processes of care between high- and low-volume providers may explain part of the observed relationship between volume and outcome.
Thrombus Formation on Atherosclerotic Plaques: Pathogenesis and Clinical Consequences
Authors: Ursula Rauch, Julio I. Osende, Valentin Fuster, Juan J. Badimon, Zahi Fayad, James H. Chesebro
Journal: Annals of Internal Medicine (2001)

Purpose: To describe the characteristics of thrombus formation on atherosclerotic plaques, the clinical expression of atherothrombosis in vascular disease, and some of the most recent therapeutic approaches in cardiovascular disease. Data Sources: MEDLINE search for English-language articles on thrombosis and atherosclerosis published up to January 2000. Abstracts of recent international meetings on new aspects of thrombus formation and new therapeutic options were reviewed, and references from identified articles were selected and reviewed. Study Selection: Experimental, basic, clinical, and epidemiologic studies related to the pathophysiology of thrombosis on atherosclerotic lesions. Therapeutic approaches were obtained from experimental studies and large clinical investigations. Data Extraction: Arterial vessel wall substrate, rheologic conditions, and blood thrombogenicity influence the process of thrombus formation in arteries. Thrombus formation on disrupted atherosclerotic plaques or arterial erosions frequently causes acute coronary syndromes. Severe atherosclerosis of the aorta has been identified as an important morphologic indicator of an increased risk for thromboembolism. Current antithrombotic therapies available as long-term treatment for patients with cardiovascular disease are often not effective enough to prevent acute thrombotic events and deterioration of atherosclerosis. Data Synthesis: Improved understanding of the pathophysiology of thrombus formation on atherosclerotic plaques has led to the development of new therapeutic approaches. Glycoprotein IIb/IIIa, tissue factor, factor Xa, and thrombin inhibitors as well as combined antithrombotic therapy, such as aspirin plus a thienopyridine plus warfarin, are being evaluated as new possible options for the treatment of arterial thrombosis. Conclusions: Long-term treatment with potent antithrombotic drugs, such as tissue factor or factor Xa inhibitors, that effectively block thrombosis without causing bleeding complications could help reduce death from cardiovascular disease.
Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function
Authors: Vassilios Papadopoulos, Mario Baraldi, Tomás R. Guilarte, Thomas B. Knudsen, Jean-Jacques Lacapère, Peter Lindemann, Michael D. Norenberg, David Nutt, Abraham Weizman, Ming-Rong Zhang, Moshe Gavish
Journal: Trends in Pharmacological Sciences (2006)
Targeting Axl With an High-affinity Inhibitory Aptamer
Authors: Laura Cerchia, Carla L Esposito, Simona Camorani, Anna Rienzo, Loredana Stasio, Luigi Insabato, Andrea Affuso, Vittorio de Franciscis
Journal: Molecular Therapy (2012)

Axl is a tyrosine kinase receptor that was first identified as a transforming gene in human myeloid leukemia. Recent converging evidence suggests its implication in cancer progression and invasion for several solid tumors, including lung, breast, brain, thyroid, and pancreas. In the last decade, Axl has thus become an attractive target for therapeutic development of more aggressive cancers. An emerging class of therapeutic inhibitors is now represented by short nucleic acid aptamers. These molecules act as high affinity ligands with several advantages over conventional antibodies for their use in vivo, including their small size and negligible immunogenicity. Furthermore, these molecules can easily form conjugates able to drive the specific delivery of interfering RNAs, nanoparticles, or chemotherapeutics. We have thus generated and characterized a selective RNA-based aptamer, GL21.T that binds the extracellular domain of Axl at high affinity (12 nmol/l) and inhibits its catalytic activity. GL21.T blocked Axl-dependent transducing events in vitro, including Erk and Akt phosphorylation, cell migration and invasion, as well as in vivo lung tumor formation in mice xenografts. In this respect, the GL21.T aptamer represents a promising therapeutic molecule for Axl-dependent cancers whose importance is highlighted by the paucity of available Axl-specific inhibitory molecules.
Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: A study using adenovirus-mediated antisense targeting
Authors: Ramiro Jover, Roque Bort, María J. Gómez‐Lechón, José V. Castell
Journal: Hepatology (2001)

Hepatocyte nuclear factor 4 (HNF4) is a member of the nuclear receptor super-family that has shown activating effects on particular cytochrome P450 (CYP) promoters from several species. However, its role in the regulation of human CYPs in the liver is still poorly understood, as no comprehensive studies in human-relevant models have been performed. In the present study, we have investigated whether HNF4 plays a general role in the expression of 7 major CYP genes in primary cultured human hepatocytes. To this end, we developed an adenoviral vector for efficient expression of HNF4 antisense RNA. Transduction of human hepatocytes with the recombinant adenovirus resulted in a time-dependent increase in the antisense transcript, followed by a concomitant decrease in apolipoprotein C III mRNA (a target gene of HNF4). Specificity was confirmed by showing that increasing levels of HNF4 antisense RNA resulted in the reduction of HNF4 protein, whereas retinoic X receptorα-(RXRα), the closest homologous member of the nuclear receptor super-family, was unaffected. Analysis of CYP gene expression in human hepatocytes transfected with HNF4 antisense RNA revealed singular behaviors: (1) CYP3A4, CYP3A5, and CYP2A6 showed an important, dose-dependent down-regulation on blockage of HNF4 translation; (2) a moderate inhibition of CYP2B6, CYP2C9, and CYP2D6 expression was observed (40%-45% reduction); (3) the levels of CYP2E1 were not affected even in the absence of this transcription factor. In conclusion, using an original strategy (efficient antisense RNA expression vector), our study shows that HNF4 is a general regulator supporting the expression of major drug-metabolizing CYPs in human hepatocytes.
P175 Mantoux or gamma Interferon (IGRA)--which test is best in children?
Authors: C. Mount, M. Helbert, C. Bell, C. Murray, F. Child
Journal: Thorax (2011)

<h3>Introduction</h3> NICE guidelines recommend a Mantoux threshold of 15 mm induration to trigger investigation for tuberculosis (TB), with IGRA tests used as second line in selected groups. Little data are available about the role of the two tests in the diagnosis of active TB. Emerging evidence suggests IGRA tests may be more sensitive in identifying TB infection in children. <h3>Aim</h3> To explore the relationship between Mantoux and IGRA in children attending a paediatric TB clinic in Manchester. <h3>Hypothesis</h3> A Mantoux threshold of ≥15 mm induration underestimates TB infection in children. <h3>Method</h3> All children aged 0–17 years referred to the TB service at Central Manchester Foundation Trust between Jan 2009 and May 2011 were included. Initial screening included symptom review and Mantoux testing. Based on induration at 48–72 h, Mantoux tests were defined as negative &lt;6 mm or positive ≥6 mm for those with no prior BCG, and negative &lt;10 mm, borderline 10 to ≥15 mm or positive ≥15 mm for those with prior BCG. Children with borderline or positive Mantoux test results, or in whom there was clinical concern, were referred for consultant assessment and/or IGRA (Quantiferon Gold). Data were collected retrospectively from case notes. <h3>Results</h3> 976 children were referred. 756 completed initial assessment (388 (51%) male, mean age 6.2±4.6 years, range 0.16–16.36 years). BCG history was known in 754 (99.7%; 516 BCG). 403 patients were discharged without intervention, 63 were offered BCG vaccination, two were referred elsewhere and 288 were referred for consultant assessment. Of these 288, 108 were notified with TB, 46 received chemoprophylaxis, 117 received no treatment, 5 received BCG and 12 failed to attend. 252 children had paired Mantoux and IGRA. Of these, 18/44 (41%) of those with a borderline Mantoux had a positive IGRA. 126/252 had TB infection (91 active and 35 latent TB)—see Abstract P175 table 1. A Mantoux threshold of ≥15 mm identified 77 (61%) children with TB infection, IGRA identified 92 (73%) and the two tests combined identified 100 (79%) children. <h3>Conclusion</h3> Using a Mantoux threshold of ≥15 mm induration significantly underestimates the number of children with TB infection compared with using Mantoux and IGRA together.
Total cholesterol and lipoproteins in school children: prediction of coronary heart disease in adult relatives.
Authors: P P Moll, C F Sing, W H Weidman, H Gordon, R D Ellefson, P A Hodgson, B A Kottke
Journal: Circulation (1983)

The distribution of risk factors and the prevalence of coronary heart disease (CHD) were studied in 850 first- and second-degree relatives of 98 healthy index cases selected from 3666 school children surveyed for lipid levels in Rochester, Minnesota. Three groups of families were based on an index child's total plasma cholesterol level: 18 families with a child in less than the fifth percentile (low-cholesterol group), 47 with a child in the fifth to ninety-fifth percentiles (middle-cholesterol group) and 33 with a child in greater than the ninety-fifth percentile (high-cholesterol group). The children's cholesterol levels clustered with those of their relatives; mortality due to CHD before age 65 was increased by 2.5 times in grandfathers of index cases in the high-cholesterol group compared with those of the middle-cholesterol group (p less than 0.016). The prevalence of CHD in all the grandfathers was associated with an index child's total cholesterol, more strongly associated with an index child's low-density lipoprotein cholesterol level and most strongly associated with an index child's high-density lipoprotein cholesterol level as a fraction of total cholesterol. This study establishes that childhood lipid and lipoprotein levels from a single cross-sectional survey identify families at elevated risk for CHD.
A piece of my mind. Yomin's star
Authors: A. Burrows
Journal: JAMA (1989)

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