tbuckley/cabot-search huggingface dataset:
Action of Thiouracil and Thyroxine Administration on Adrenal Function
Authors: J. Corvilain
Journal: BMJ (1953)

<i>Abstract</i>. Although it is widely known that many macrophages are present in glomeruli of antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis (ANCA + RV) and are believed to contribute to necrotizing extracapillary damage, their precise role is not yet completely understood, especially in humans. The goal of this study was to provide evidence of glomerular macrophage properties in human vasculitis. Twenty-five renal biopsies of ANCA + RV and 18 cases of cryoglobulinemic glomerulonephritis (cryoGN), a disease characterized by massive glomerular macrophage infiltration but absence of necrotizing extracapillary lesions, were selected, and macrophage number, adhesion, acute activation, proliferation, and apoptosis were analyzed by immunohistochemistry and <i>in situ</i> hybridization. Accumulation of macrophages in ANCA + RV was found in areas of glomerular active lesions, whereas in cryoGN, they homogeneously occupied the entire glomerular tuft. Considering the areas of accumulation, comparable macrophage numbers were detected in both diseases. Glomerular vascular cell adhesion molecule-1 was found only in ANCA + RV and only in areas of active lesions. Acute macrophage activation (HLA class II, 27E10) and proinflammatory cytokine production (tumor necrosis factor-α, interleukin-1α) were prominent in ANCA + RV, whereas in cryoGN, 30% of glomerular macrophages seemed activated and cytokine expression was limited to a few glomerular cells (<i>P</i> = 0.01). Moreover, only in ANCA + RV proliferative markers were shown on glomerular macrophages and apoptotic macrophages were found. From the data, it seems that ANCA + RV and cryoGN differ profoundly in macrophage properties, namely adhesion, proliferation, and apoptotic clearance. Moreover, acute activation and cytokine production seem to be present in a greater number of macrophages in ANCA + RV, giving this disease a stronger severity that could be taken into account for therapeutic strategies.
Evaluation of a Structured Outpatient Group Education Program for Intensive Insulin Therapy
Authors: Thomas R Pieber, Gernot A Brunner, Wolfgang J Schnedl, Susanne Schattenberg, Peter Kaufmann, Guenter J Krejs
Journal: Diabetes Care (1995)

OBJECTIVE To determine the efficacy and safety of a structured diabetes teaching and treatment program (DTTP) in patients with insulin-dependent diabetes mel-litus (IDDM) in an outpatient setting. RESEARCH DESIGN AND METHODS All patients with IDDM who completed a structured 5-day outpatient DTTP were reevaluated after a mean follow-up of 3 years. A standardized interview was used to assess frequency of severe hypoglycemia, type of insulin treatment, self-monitoring, and other diabetes-related parameters. HbA1c was measured by high-performance liquid chromatography. RESULTS Of 205 patients, 4 (2%) died during the observation period. HbA1c in the 201 surviving patients decreased significantly from 8.7 ± 2.0 to 7.5 ± 1.2% at follow-up (P &amp;lt; 0.001); frequency of severe hypoglycemia decreased from a mean of 0.46 to 0.13 per patient per year (P &amp;lt; 0.001). Hospital admission due to acute metabolic disturbances decreased from 4.5 ± 11.1 to 1.4 ± 6.7 days/patient-year (P &amp;lt; 0.001). At follow-up, intensive insulin therapy was carried out by 98% of the patients, and 80% of the patients reported three or more measurements of blood glucose per day. Diabetes-related knowledge had a positive (P &amp;lt; 0.01) and body mass index a negative (P &amp;lt; 0.02) influence on improving HbA1c assessed by multiple regression analysis. Severe hypoglycemia after DTTP was associated with a history of severe hypoglycemia before DTTP (P &amp;lt; 0.001) and the existence of overt diabetic nephrop-athy (P &amp;lt; 0.05). CONCLUSIONS A structured outpatient DTTP as used in this study is able to improve overall metabolic control and decrease the frequency of severe hypoglycemia in patients with IDDM.
FLT3 Kinase Inhibitor TTT-3002 Overcomes Both Activating and Drug Resistance Mutations in FLT3 in Acute Myeloid Leukemia
Authors: Hayley S. Ma, Bao Nguyen, Amy S. Duffield, Li Li, Allison Galanis, Allen B. Williams, Patrick A. Brown, Mark J. Levis, Daniel J. Leahy, Donald Small
Journal: Cancer Research (2014)

There have been a number of clinical trials testing the efficacy of FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) in patients with acute myeloid leukemia (AML) harboring a constitutively activating mutation in FLT3. However, there has been limited efficacy, most often because of inadequate achievement of FLT3 inhibition through a variety of mechanisms. In a previous study, TTT-3002 was identified as a novel FLT3 inhibitor with the most potent activity to date against FLT3 internal tandem duplication (FLT3/ITD) mutations. Here, the activity of TTT-3002 is demonstrated against a broad spectrum of FLT3-activating point mutations, including the most frequently occurring D835 mutations. The compound is also active against a number of point mutations selected for in FLT3/ITD alleles that confer resistance to other TKIs, including the F691L gatekeeper mutation. TTT-3002 maintains activity against patients with relapsed AML samples that are resistant to sorafenib and AC220. Studies utilizing human plasma samples from healthy donors and patients with AML indicate that TTT-3002 is only moderately protein bound compared with several other TKIs currently in clinical trials. Tumor burden of mice in a FLT3 TKI-resistant transplant model is significantly improved by oral dosing of TTT-3002. Therefore, TTT-3002 has demonstrated preclinical potential as a promising new FLT3 TKI that may overcome some of the limitations of other TKIs in the treatment of FLT3-mutant AML. Cancer Res; 74(18); 5206-17. ©2014 AACR.
Cardiovascular Morbidity and Mortality in Women Diagnosed With Rheumatoid Arthritis
Authors: Daniel H. Solomon, Elizabeth W. Karlson, Eric B. Rimm, Carolyn C. Cannuscio, Lisa A. Mandl, JoAnn E. Manson, Meir J. Stampfer, Gary C. Curhan
Journal: Circulation (2003)

Background— Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease. We compared the incidence rates of myocardial infarction and stroke in subjects with and without rheumatoid arthritis. Methods and Results— A prospective cohort study was conducted among the 114 342 women participating in the Nurses’ Health Study who were free of cardiovascular disease and rheumatoid arthritis at baseline in 1976. All self-reported cases of rheumatoid arthritis were confirmed by medical record review. Fatal and nonfatal myocardial infarctions and strokes were similarly confirmed. Multivariate pooled logistic regression was used to adjust for potential cardiovascular risk factors. Five hundred twenty-seven incident cases of rheumatoid arthritis and 3622 myocardial infarctions and strokes were confirmed during 2.4 million person-years of follow-up. The adjusted relative risk of myocardial infarction in women with rheumatoid arthritis compared with those without was 2.0 (95% confidence interval [CI], 1.23 to 3.29). For stroke, the adjusted relative risk was 1.48 (95% CI, 0.70 to 3.12). Women who had rheumatoid arthritis for at least 10 years had a risk for myocardial infarction of 3.10 (95% CI, 1.64 to 5.87). Conclusion— In this large prospective cohort of women, participants with rheumatoid arthritis had a significantly increased risk of myocardial infarction but not stroke compared with those without rheumatoid arthritis. If these data are confirmed, aggressive coronary heart disease prevention strategies should be tested for persons with rheumatoid arthritis.
The Brainstorms Village: Epilepsy in our World
Authors: E H Reynolds
Journal: BMJ (2004)

Is the subjective experience of epilepsy and its treatment in different social and cultural settings important in understanding, managing, supporting, researching, and preventing the disorder? Undoubtedly, as it is with other acute and chronic disorders. But as the authors of this book emphasise, epilepsy is a special case with its universality, ubiquity, variability, consciousness-interrupting paroxysms, misunderstanding, social impact, and historical legacy.

Eds Steven C Schachter, Lisa Francesca Andermann

Lippincott Williams & Wilkins, …
A NEW INCISION FOR THE SURGERY OF THE BILE TRACTS.
Authors: A. D. BEVAN
Journal: JAMA (1897)

The subject of the surgery of bile tracts is of recent development. In 1867 Bobbs of Indiana performed cholecystotomy. In 1882 Langenbuch removed the gall bladder, cholecystectomy. In the same year Gaston suggested cholecystenterostomy, which was later perfected by the introduction of the anastomosis button by Murphy. In 1890 Courvoisier performed and advocated choledochotomy, and later the removal of stones from the cystic duct and hepatic duct were reported. In the last five years the value and possibilities of the surgery of the bile tracts has been so thoroughly demonstrated, that it is today a recognized field to all men doing abdominal work. A few years ago, when I began to do surgical work on the bile tracts, I carefully reviewed the topographic anatomy of this region. I was surprised to find how completely the subject had been neglected by both anatomists and surgeons. And here let me say a
Veterans Administration Coronary Cooperative Study
Authors: Joseph S. Carey
Journal: JAMA (1979)

THE DEBATE on the merits of coronary artery bypass continues on in editorial pages, most recently in<i>JAMA</i><sup>1</sup>and in the<i>American Journal of Cardiology</i>.<sup>2</sup>The debate was initiated by Eugene Braunwald, MD, in September 1977, when he suggested that "coronary arteriography is not always resisted vigorously" by practicing physicians caring for patients with angina pectoris. Braunwald<sup>3</sup>also said that a more insidious problem is that an industry has been built around the coronary artery bypass procedure. Dr Braunwald's comment was based on a preliminary report of a Veterans Administration Cooperative Study, which suggested that in male veterans with chronic stable angina, coronary artery bypass surgery did not prolong survival. This report has now been disputed by its own participants<sup>4</sup>and by several nonparticipating hospitals.<sup>5-7</sup>Wadsworth VA (Los Angeles) and San Francisco VA hospitals, both of which dropped out of the cooperative study in 1972,
Medical students may not like statistics, but as doctors they will
Authors: R Rozzini, S Franzoni, G Frisoni, M Trabucchi
Journal: BMJ (1998)

EDITOR—In his book review, Wessely finds Sinclair's analysis of medical education in Making Doctors depressing because Sinclair reports that medical students regard the psychiatrist as “the lowest form of medical life.”1 Further, they do this because of the very things of which Wessely is rightly proud: psychiatrists' use of a …
Jejunoileal Shunt for Obesity
Authors: Jules Hirsch
Journal: New England Journal of Medicine (1974)

This issue of the Journal carries an article on protein nutrition and liver disease after jejunoileal bypass done for the treatment of obesity. Intestinal surgery for the obese is becoming increasingly popular. One of the first reports, over 10 years ago,1 was a detailed study of 10 patients who first received a jejunocolic bypass and after loss to ideal or near ideal weights, were reoperated on to establish normal intestinal continuity. Since that time, other reports have appeared with appropriate refinements in surgical technic to permit a permanent shunt between jejunum and ileum, thereby achieving equilibration of weight at a . . .
Restoring p53 Function in Human Melanoma Cells by Inhibiting MDM2 and Cyclin B1/CDK1-Phosphorylated Nuclear iASPP
Authors: Min Lu, Hilde Breyssens, Victoria Salter, Shan Zhong, Ying Hu, Caroline Baer, Indrika Ratnayaka, Alex Sullivan, Nicholas R. Brown, Jane Endicott, Stefan Knapp, Benedikt M. Kessler, Mark R. Middleton, Christian Siebold, E. Yvonne Jones, Elena V. Sviderskaya, Jonathan Cebon, Thomas John, Otavia L. Caballero, Colin R. Goding, Xin Lu
Journal: Cancer Cell (2013)
Detailed comparison of basal and food-stimulated gastric acid secretion rates and serum gastrin concentrations in duodenal ulcer patients and normal subjects.
Authors: A J Blair, M Feldman, C Barnett, J H Walsh, C T Richardson
Journal: Journal of Clinical Investigation (1987)

We measured basal and peak acid outputs, food-stimulated acid secretion, and basal and food-stimulated serum gastrin concentrations in a large group of duodenal ulcer patients and normal subjects. Basal and peak acid outputs were significantly higher in ulcer patients. In contrast, acid secretion was similar in the groups when food was infused into the stomach and when sham feeding was combined with meal infusion to simulate normal eating. Meal-stimulated acid secretion, expressed as a percentage of peak acid output to correct for differences in secretory capacity, was lower in ulcer patients (P less than 0.002). Basal serum gastrin concentrations were higher in ulcer patients, which may have contributed to higher basal acid output. However, increases in serum gastrin after food were similar in the groups. Duodenal ulcer patients, as a group, have increased basal and maximal acid secretion, but the amount of acid secreted and gastrin released after eating is normal.
Thrombin activatable fibrinolysis inhibitor (TAFI) levels in patients with coronary artery disease investigated by anglography
Authors: Tushar Chatteriee, Verena Schroeder, Martin Fleisch, Stefan Windecker, Christian Seiler, Franz R. Ebarli, Bernhard Meier, Hans P. Kohler
Journal: Journal of the American College of Cardiology (2002)
Prospective Study of Recreational Physical Activity and Ovarian Cancer
Authors: E. R. Bertone, W. C. Willett, B. A. Rosner, D. J. Hunter, C. S. Fuchs, F. E. Speizer, G. A. Colditz, S. E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: It has been hypothesized that physical activity may reduce the risk of ovarian cancer by decreasing estrogen levels, reducing body fat, and reducing the frequency of ovulation. Epidemiologic studies of this relationship have obtained inconsistent results. The only prospective study to date reported a positive association between frequent vigorous exercise and ovarian cancer risk. We further evaluated this relationship in the Nurses' Health Study cohort. Methods: Participation in recreational physical activity was assessed by questionnaire in 1980, 1982, 1986, 1988, 1992, and 1994, with questions assessing exercise frequency, duration, and intensity. Results were adjusted for age, parity, oral contraceptive use, tubal ligation, and other risk factors for ovarian cancer. All statistical tests were two-sided. Results: During a 16-year follow-up (from 1980 to 1996), 1.2 million person-years were accrued by 92 825 cohort members, and 377 cases of epithelial ovarian cancer were confirmed. The relative risk (RR) of ovarian cancer for women engaging in recreational physical activity for 7 hours or more per week compared with those reporting less than 1 hour per week was 0.80 (95% confidence interval [CI] = 0.49 to 1.32; Ptrend = .59). When both the frequency and intensity of activity were taken into account, activity level was also not associated with a reduced risk of ovarian cancer. Compared with inactive women, participants reporting high activity in terms of metabolic equivalent task hours (MET hours) were at greater risk of ovarian cancer (RR for 20 to <30 MET hours/week = 1.84 [95% CI = 1.12 to 3.02]; RR for >30 MET hours/week = 1.27 [95% CI = 0.75 to 2.14]). Conclusions: Overall, results did not suggest an inverse association between recreational physical activity and ovarian cancer. The possibility of a modest increase in risk with frequent vigorous activity requires further investigation.
Two-dimensional in vivo pressure/diameter relationships in the canine main pulmonary artery
Authors: T. A JOHNSON, G W. HENRY, C. L LUCAS, B. A KEAGY, M. E LORES, H. S HSIAO, J. I FERREIRO, B. R WILCOX
Journal: Cardiovascular Research (1985)

Ultrasonic measurement of blood flow within the main pulmonary artery (MPA) requires a precise knowledge of the mean blood velocity within this vessel and the cross-sectional area (CSA). Small conformational changes in the elliptical shape of the MPA have substantial effects on the calculation of CSA and, subsequently, flow. We examined the extent of these changes by measuring the pulsatile and mean elliptical dimensions of the MPA in nine anaesthetised, open-chested, mechanically ventilated mongrel dogs using two pairs of 10 MHz ultrasonic, piezoelectric crystals. These custom-made devices were sutured to the PA adventitia along the long and short cross-sectional axes 2 cm distal to the pulmonary valve. Axial dimensions were collected during normal, elevated (via noradrenaline and fluid additions) and reduced (via exsanguination) PA pressures. We confirmed the linear pressure/diameter response in 15/18 axial data sets (r greater than 0.80). Further, the linear axial responses of the long and short diameters were parallel (7/9, p less than 0.05) and have different zero-pressure intercepts (7/9, p less than 0.0001). A mathematical consequence of this parallelism is predictable, although non-constant, eccentricity. Finally, error analysis of multi-axial measurement techniques were shown to improve CSA accuracy by as much as 50% when compared with uni-axial determinations.
A patient with bilateral shoulder and pelvic girdle aching
Authors: L. H. G. Henskens, N. Broos, K. Hautermans
Journal: BMJ (2011)

A 67 year old man, with a history of hypertension controlled with irbesartan with hydrochlorothiazide 300 and 12.5 mg/day, presented to his general practitioner with subacute onset of symmetrical aching and stiffness (most extreme in the morning) in his shoulders, pelvic girdle, and to a lesser extent his hands and knees, six days earlier. As a result, he had great difficulty turning over in bed, rising from a chair, and raising his arms above shoulder height. He also reported malaise and insomnia. He had no fever or other recent health problems. Twenty four hours before the onset of symptoms he had received the seasonal flu vaccine (Influvac 2009-10: A/Brisbane/59/2007, A/Brisbane/10/2007, B/Brisbane 60/2008). 

Physical examination showed that he had difficulty raising his arms above shoulder height and rising from a chair. Both active and passive movements of the shoulders and hips were restricted because of muscle pain. Muscle weakness, erythema, and joint swelling were all absent. The temporal arteries seemed normal to palpation.

Biochemical investigations yielded an erythrocyte sedimentation rate of 7 mm in the first hour (reference range <20.0 mm), a C reactive protein concentration of 18 mg/L (<5), and a mild leucocytosis of 12.2×109/L (4.0-10.0). Red blood cells, haemoglobin, thyroid hormones, aminotransferases, and creatinine kinase were all normal. Anticyclic citrullinated protein antibodies were absent. We presumed a diagnosis of myalgia caused by viral infection or related to immunisation with flu vaccine and started him on a non-steroidal inflammatory drug (diclofenac 100 mg twice daily). After three weeks, however, symptoms had not improved.



### 1 What is the most likely diagnosis?

#### Short answer

The …
Cholesteryl esters from oxidized low-density lipoproteins are in vivo rapidly hydrolyzed in rat kupffer cells and transported to liver parenchymal cells and bile
Authors: Moniek N. Pieters, Sebastiaan Esbach, Donald Schouten, Adriaan Brouwer, Dick L. Knook, Theo J. C. Van Berkel
Journal: Hepatology (1994)

Human low-density lipoprotein was labeled in its cholesteryl ester moiety with [3H]cholesteryl oleate or [3H]cholesteryl oleoyl ether and oxidized by exposure to 10 mumol/L of cupric sulfate. The in vivo metabolism of cholesteryl esters of oxidized low-density lipoprotein was determined after injection into rats. When oxidized low-density lipoprotein was labeled with [3H]cholesteryl oleoyl ether, a nonhydrolyzable analog of cholesteryl oleate, Kupffer cells contributed to 55.1% +/- 4.1% of the total liver uptake 10 min after injection. When [3H]cholesteryl oleate-labeled oxidized low-density lipoprotein was injected, the radiolabeled cholesterol esters were nearly completely hydrolyzed within 1 hr of injection. Within this time, the Kupffer cell-associated radioactivity declined to 32% of the maximal uptake value. In serum, the highest specific resecreted [3H]cholesteryl (esters) were associated with the serum high-density lipoprotein fraction, suggesting a role for high-density lipoprotein as an in vivo cholesterol acceptor. The kinetics of biliary secretion were studied in rats equipped with catheters in the bile duct, duodenum and heart. One hour after injection of [3H]cholesteryl oleate-labeled oxidized low-density lipoprotein, 4.15% +/- 0.67% of the injected dose was secreted in the bile, mainly as bile acids. Six hours after injection, this value was 19.2% +/- 1.2%. These values are three times higher than those for injected [3H]cholesteryl oleate-labeled acetylated low-density lipoprotein, which is initially mainly taken up by liver endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of Molecular Vulnerabilities in Human Multiple Myeloma Cells by RNA Interference Lethality Screening of the Druggable Genome
Authors: Rodger E. Tiedemann, Yuan Xao Zhu, Jessica Schmidt, Chang Xin Shi, Chris Sereduk, Hongwei Yin, Spyro Mousses, A. Keith Stewart
Journal: Cancer Research (2011)

Abstract Despite recent advances in targeted treatments for multiple myeloma, optimal molecular therapeutic targets have yet to be identified. To functionally identify critical molecular targets, we conducted a genome-scale lethality study in multiple myeloma cells using siRNAs. We validated the top 160 lethal hits with four siRNAs per gene in three multiple myeloma cell lines and two non-myeloma cell lines, cataloging a total of 57 potent multiple myeloma survival genes. We identified the Bcl2 family member MCL1 and several 26S proteasome subunits among the most important and selective multiple myeloma survival genes. These results provided biologic validation of our screening strategy. Other essential targets included genes involved in RNA splicing, ubiquitination, transcription, translation, and mitosis. Several of the multiple myeloma survival genes, especially MCL1, TNK2, CDK11, and WBSCR22, exhibited differential expression in primary plasma cells compared with other human primary somatic tissues. Overall, the most striking differential functional vulnerabilities between multiple myeloma and non–multiple myeloma cells were found to occur within the 20S proteasome subunits, MCL1, RRM1, USP8, and CKAP5. We propose that these genes should be investigated further as potential therapeutic targets in multiple myeloma. Cancer Res; 72(3); 757–68. ©2011 AACR.
948-52 Paradoxical Neurohumoral Axis Inhibition After Body Fluid Volume Depletion in Patients with Congestive Heart Failure and Water Retention
Authors: Maurizio D. Guazzi, Piergiuseppe Agostoni, G. Battista Perego, Gianfranco Lauri, Francesco Giraldi, Marco Matturri, Marco Guazzi, Giancarlo Marenzl
Journal: Journal of the American College of Cardiology (1995)
Changes in conjugated linoleic acid and its metabolites in patients with chronic renal failure
Authors: Leonardo Lucchi, Sebastiano Banni, Maria P. Melis, Elisabetta Angioni, Gianfranca Carta, Viviana Casu, Renato Rapanà, Angela Ciuffreda, Francesco P. Corongiu, Alberto Albertazzi
Journal: Kidney International (2000)