tbuckley/cabot-search huggingface dataset:
Abstract 3589: Dovitinib (TKI258), a multikinase inhibitor of FGFR, PDGFR, and VEGFR tyrosine kinases, induces growth inhibition in endometrial carcinoma cells
Authors: Gottfried E. Konecny, Boris Winterhoff, Ellen Yang Guorong, Jingwei Qi, Julie Le, Michael Shi, Margaret Dugan, Ronald Linnartz, Richard S. Finn, Dennis J. Slamon
Journal: Cancer Research (2011)

Abstract Background: Endometrial carcinoma is the most common gynecological malignancy in the western world. Activating mutations of the fibroblast growth factor receptor 2 (FGFR2) have been described in 12-16% of endometrial cancers. Moreover, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) and their receptors are involved in the neovascularization, invasiveness, and metastatic potential of endometrial cancer. Therefore, suppression of FGFR/VEGFR/PDGFR signaling by TKI258 may represent a novel approach for treatment of endometrial cancer. Experimental Design: The aims of this study were 1.) to assess the effect of TKI258 on tumor cell growth in two-dimensional (2D) and three-dimensional (3D) culture assays using a panel of 20 human endometrial cancer cell lines, 2.) to identify candidate molecular markers predicting sensitivity using baseline gene expression profiling and mutational analyses, and 3.) to determine the in vivo antineoplastic activity of TKI258 in endometrial cancer xenograft models. In addition, we screened 200 fresh frozen endometrial cancer specimens to comprehensively assess the distribution pattern of PI3K, PTEN, and FGFR mutations in endometrial cancer. Results: Concentration-dependent anti-proliferative effects of TKI285 using 2D assays were seen in all endometrial cancer cell lines tested, but varied significantly between individual cell lines (IC50 range: 0.42µM – 3.06 µM). The three most sensitive endometrial cancer cell lines demonstrated activating FGFR2 mutations (MFE296: N549K, IC50 0.42µM; AN3CA: N549K and K310R, IC50 0.50µM; MFE280: S252W, IC50 0.66µM). Assessment of TKI258 responses in 3D assays demonstrated similar results to those observed in 2D culture assays in that the 3 cell lines harboring FGFR2 mutations were the most sensitive to TKI258 achieving 100% growth inhibition at a concentration of 1µM. AN3CA and MFE296 endometrial cancer cells formed xenografts in nude mice and antitumor activity was studied in both models. Inhibition of p-FGFR, p-PDGFR, p-VEGFR-2, pAKT and p-ERK1/2 were observed. Comprehensive data on the pattern of PI3K, PTEN and FGFR mutations in endometrial cancer will be provided. Conclusion: TKI258 demonstrates significant antitumor activity in endometrial cancer cells with FGFR2 mutations. This study provides a strong rationale for the clinical evaluation of TKI258 in patients with endometrial cancer, specifically in those harboring FGFR2 mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3589. doi:10.1158/1538-7445.AM2011-3589
Hepatic trapping of red cells in canine endotoxin shock: a variable phenomenon after splenectomy
Authors: G J J TEULE, A D M KESTER, P D BEZEMER, L J THIJS, G A K HEIDENDAL
Journal: Cardiovascular Research (1985)

We studied in 20 splenectomised dogs the incidence of early intravascular hepatic pooling after administration of E. coli endotoxin. Autologous red cells were labelled in vitro with 99mTc. Bloodpool imaging and haemodynamic measurements were performed simultaneously. Changes in hepatic red cell volume were estimated from alterations in hepatic activity. In 10 dogs, hepatic red cell activity increased considerably (156 to 359% of the basal value). In the remaining animals the hepatic activity did not change markedly or even decreased. The decline in arterial pressure and cardiac output seemed more pronounced in dogs with clear evidence of hepatic pooling. However no significant differences in absolute haemodynamic values could be demonstrated between dogs with and without pooling. It is concluded that an hepatic outflow block is not a constant feature of canine endotoxin shock. Absolute haemodynamic values do not depend on the presence of an outflow block. Thus the presence of hepatic pooling need not make the canine model inappropriate for studies on human sepsis.
Cancer of the Cervix
Authors: Bruce M. Rodenberger, Ralph P. Earle, Theodore H. Ingalls
Journal: New England Journal of Medicine (1966)

CLINICAL experience with women who had participated in a program of annual physical examinations, which included cervical cytologic smears stained by the Papanicolaou technic, in the relatively closed population on the island of Vinalhaven, Maine (Fig. 1), led, in 1961, to the impression that the incidence of carcinoma was higher than was to be expected among these women.1 However, since persons studied comprised only about a third of the more than 400 women over twenty-one years of age who made up the total adult female population, absolute numbers were not large, and expectancies would be greatly influenced by the proportion . . .
OPTIC ATROPHY FROM LEAD POISONING
Authors: R. J. Reitzel
Journal: JAMA (1931)

A Negro girl baby, aged 19 months, was admitted to the pediatric service of the John Sealy Hospital, May 15, 1929, because of vomiting, muscular weakness and irritability. The baby had been delivered at full term by cesarean section. Her weight was 5½ pounds (2.5 Kg.), and her condition was good. She sat alone and began teething at 7 months, talked at 1 year of age and walked at 13 months. Feeding was artificial on a cow's milk formula. Later on she took cereals and cod liver oil. Prior to the present illness, she had always been well. The family history was negative. Three months before entering the hospital the baby began rubbing her nose with her hands, and began vomiting. The vomiting had no especial relation to meals. Later on there was excessive crying. One month later the eyes "became crossed," she stopped talking, and she was unable to
Psychiatry in Britain
Authors: H. J. WALTON
Journal: American Journal of Psychiatry (1966)

The National Health Service has become the work setting for most British psychiatrists; of the main subspecialties only psychoanalysis remains outside. Only about five percent of first admissions to hospitals with a diagnosis of schizophrenia now become long-stay patients, contrasted with 70 percent in 1930. Discharge to the community has not created a problem. Hospital and community psychiatrists, teachers of psychiatry, and researchers share a mood of lively self-appraisal which also contains an openness to new knowledge and a readiness for necessary change.
Political Realities and Biomedical Research
Authors: Andrew Burness
Journal: JAMA (1980)

AT a conference on the future of clinical research, a medical school dean dramatized the communication gap between the medical research community and federal government. He told the story of the reluctant rabbi who sheepishly tried to convince the Pope that some land in question belonged to the Jews. Since the rabbi spoke no Italian and the Pope no Hebrew, they were forced to negotiate in sign language. After a while, the Pope became impressed with the rabbi's profound insight. But when the rabbi took out an apple in response to the Pope's bread and wine, the Holy Father was convinced. He turned to his followers, saying, "This rabbi is smarter than I.I reveal the body and blood of the Christ, and he takes out an apple, the symbol of life itself. The Jews may have the land." The rabbi was greeted with incredible joy on his return to the
FETAL DAMAGE DESPITE LOW-PHENYLALANINE DIET AFTER CONCEPTION IN A PHENYLKETONURIC WOMAN
Authors: Isabel Smith, F.J. Macartney, M. Erdohazi, J.R. Pincott, O.H. Wolff, D.P. Brenton, S.A. Biddle, D.V.I. Fairweather, J. Dobbing
Journal: The Lancet (1979)
Benefit of using polymerase chain reaction to test blood donations will be considerable
Authors: J. Barbara
Journal: BMJ (1997)

Editor—It is unfortunate that in attempting to summarise a complex situation regarding the potential role of the polymerase chain reaction in blood transfusion Adam Legge has overinterpreted my views.1 Although undoubtedly more costly than serological testing, use of the polymerase chain reaction does not involve a “quantum leap” in cost, …
Serum CD23 is not altered in gastroall_ergic anisakiasis, but correlates with the production of specific IgE and the amount of polyclonal stimulation
Authors: A. Daschner, C. Cuéllar, A. Alonso‐Gómez, C. Y. Pascual, M. Martín‐Esteban
Journal: Allergy (2001)

Background: Previous studies have shown elevated serum levels of the cytokines IL‐4 and sCD23 in atopic patients and parasitic disease. Gastroall_ergic anisakiasis is an acute parasitic disease, accompanied by IgE‐mediated clinical symptoms and an important increase of specific and total IgE. Methods: Sixteen patients with acute urticaria/angioedema due to parasitism by Anisakis simplex after intake of raw or undercooked fish were selected, and serum samples were taken in the emergency room within 24 h (day 0; n =16), after 1 month ( n =16), and after 6 months ( n =10). Serum samples were studied for specific IgE against A. simplex , total IgE, sCD23, and IL‐4. Results: Mean values for sCD23 did not change in the observation period. Only 4/16 serum samples showed measurable IL‐4 levels. Specific IgE and total IgE levels were found to be elevated after 1 month; after 6 months, they fell to nearly basal values. There was a positive correlation between sCD23 and specific IgE at day 0 and follow‐up ( r =0.55–0.69, P &lt;0.026); a positive correlation beween sCD23 and total IgE ( r =0.54–0.62, P &lt;0.056). Basal sCD23 could moderately predict the percentual increment of total IgE in the first month ( r =0.56, P &lt;0.038). Conclusions: Thus, it seems that interindividual variability of sCD23 is an important factor, with higher values predisposing to more production of unrelated IgE, independently of the parasite's action.
A Prospective Randomized Study Comparing the Effects of Large and Small Volumes of the Sclerosant 5 % Ethanolamine Oleate Injected into Esophageal Varices
Authors: Y. Iso, S. Kitano, T. Iwanaga, N. Koyanagi, K. Sugimachi
Journal: Endoscopy (1988)

The safety efficacy and complications of injections of large and small volumes of 5% ethanolamine oleate (EO) were examined prospectively in the sclerotherapy of esophageal varices in 39 consecutive cirrhotic patients. Twenty patients were randomly allocated to the large-volume group (LVG) injected with up to 30 ml per session, and 19 to the small-volume group (SVG) injected with up to 15 ml per session. The two groups were comparable with regard to age, etiology and severity of liver disease. Post-injection bleeding occurred in 15.8% (3/19) after 1-3 sessions in the SVG and in 0% in the LVG. The LVG showed a significantly higher rate of decrease in variceal size (95.0% vs 53.2%, p less than 0.05) and disappearance of red color signs (RCS) on the variceal surface (95.0% vs 52.6%, p less than 0.01) one week after the initial session. The treatment period and number of sessions of endoscopic injection sclerotherapy (EIS) for eradication of varices were significantly (p less than 0.01) smaller in LVG than in SVG (LVG: 2.7 +/- 0.6 sessions over 4.2 +/- 0.7 weeks vs SVG: 5.4 +/- 0.9 sessions over 6.0 +/- 1.6 weeks). There were no life-threatening complications, and the incidence of minor complications did not differ between the two groups. The persistence of RCS and the occurrence of post-injection bleeding may imply that esophageal varices are not always completely obliterated despite 1-3 sessions in the SVG. We conclude that the large volume of EO is superior to the small volume for repeated EIS to eradicate esophageal varices.
Long-term Correction of Very Long-chain Acyl-CoA Dehydrogenase Deficiency in Mice Using AAV9 Gene Therapy
Authors: Allison M Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott A Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence R Flotte
Journal: Molecular Therapy (2012)

Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 × 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of intramuscular lipids in treated animals. Correction was not observed in liver tissue extracts, but cardiac muscle extracts showed significant reduction of long-chain metabolites. Disease-specific phenotypes were characterized, including thermoregulation and maintenance of euglycemia after a fasting cold challenge. Internal body temperatures of untreated VLCAD(-/-) mice dropped below 20 °C and the mice became lethargic, requiring euthanasia. In contrast, all rAAV9-treated VLCAD(-/-) mice and the wild-type controls maintained body temperatures. rAAV9-treated VLCAD(-/-) mice maintained euglycemia, whereas untreated VLCAD(-/-) mice suffered hypoglycemia following a fasting cold challenge. These promising results suggest rAAV9 gene therapy as a potential treatment for VLCAD deficiency in humans.
Local Effects of Intramuscular Solvochin
Authors: F. Hawking
Journal: BMJ (1945)

preferable to lethane because one treatment properly carried out should cure every case.This substance will not, however, be avail- able till after the war.Lethane will cure a large proportion of cases with one application, but two treatments at a week's interval will give certain cure.In order to obtain good results the details of the application of lethane should be carefully observed.Two or three teaspoonfuls of the oil are used for one treatment.The hair is parted, and 2 or 3 drops from the teaspoon or pipette are dripped on to the scalp.This is repeated in from 12 to 20 different areas all over the scalp.With the finger-tips the scalp is vigorously rubbed for two minutes to ensure equal distribution of the oil.Any oil which trickles down the forehead or behind the ears should be wiped off with cotton-wool and vaseline applied.The following substances proved ineffective in the treatment of pediculosis: 20% solution of dettol, derbac soap, concentrated infusion of quassia, 12.5% formalin soap mixture (M.O.H. Memo., 1940), 0.1°, aqueous solution of mercuric chloride, oils of cedar- wood, citronella, and lemon-grass, and lauryl thiocyanate.
Institutional and editorial misconduct in the MMR scare
Authors: F. Godlee
Journal: BMJ (2011)

This week, in the last of his series of three articles on the secrets of the MMR scare (doi:10.1136/bmj.c7001), Brian Deer describes the events of 2004 when he first raised concerns about Andrew Wakefield’s research with the Lancet ’s editor. Rather than calling for an investigation as Deer had expected, Richard Horton moved quickly—with Wakefield, his co-authors, and their former institution—to publicly deny all but one of Deer’s allegations. Six years later, at an estimated cost of £6m, the General Medical Council found all the allegations to be true.

In his observations column, Harvey Marcovitch asks again why it took so long to uncover Wakefield’s fraud (doi:10.1136/bmj.d284). He compares it with other major …
Primary care complex offering public and private healthcare to 30 000 opens in Somerset
Authors: G. Iacobucci
Journal: BMJ (2013)

A new health complex providing primary and secondary care services to tens of thousands of patients under one roof has officially opened its doors.

The £10.5m (€12.9m; $16.9m) Frome Medical Centre, developed in a new purpose built complex in the Somerset town, will house 130 health professionals, including more than 30 GPs and a host of consultants—making it one of the biggest integrated primary care buildings in the United Kingdom.

The centre, which has been in development for more than a decade, …
LSP1 is an endothelial gatekeeper of leukocyte transendothelial migration
Authors: Lixin Liu, Denise C. Cara, Jaswinder Kaur, Eko Raharjo, Sarah C. Mullaly, Jenny Jongstra-Bilen, Jan Jongstra, Paul Kubes
Journal: The Journal of Experimental Medicine (2005)

Leukocyte-specific protein 1 (LSP1), an F-actin binding protein and a major downstream substrate of p38 mitogen-activated protein kinase as well as protein kinase C, has been reported to be important in leukocyte chemotaxis. Although its distribution has been thought to be restricted to leukocytes, herein we report that LSP1 is expressed in endothelium and is essential to permit neutrophil emigration. Using intravital microscopy to directly visualize leukocyte rolling, adhesion, and emigration in postcapillary venules in LSP1-deficient (Lsp1−/−) mice, we found that LSP1 deficiency inhibits neutrophil extravasation in response to various cytokines (tumor necrosis factor-α and interleukin-1β) and to neutrophil chemokine keratinocyte-derived chemokine in vivo. LSP1 deficiency did not affect leukocyte rolling or adhesion. Generation of Lsp1−/− chimeric mice using bone marrow transplantation revealed that in mice with Lsp1−/− endothelial cells and wild-type leukocytes, neutrophil transendothelial migration out of postcapillary venules is markedly restricted. In contrast, Lsp1−/− neutrophils in wild-type mice were able to extravasate normally. Consistent with altered endothelial function was a reduction in vascular permeability to histamine in Lsp1−/− animals. Western blot analysis and immunofluorescence microscopy examination confirmed the presence of LSP1 in wild-type but not in Lsp1−/− mouse microvascular endothelial cells. Cultured human endothelial cells also stained positive for LSP1. Our results suggest that LSP1 expressed in endothelium regulates neutrophil transendothelial migration.
Forceps Biopsy of the Bile Duct under Choledochoscopic Control
Authors: A. Nishimura, H. Otsu, T. Hiura
Journal: Endoscopy (1980)

Forceps biopsy of the distal part of the common bile duct was performed in 27 patients with cholelithiasis, under choledochoscopic guidance during surgery. Significant choledochitis was diagnosed in 72 per cent of the patients, including two with carcinoma of the head of the pancreas. Two patients with carcinoma of the head of the pancreas underwent biopsy in an attempt to obtain evidence of neoplasm. Furthermore, one patient suspected of carcinoma of the left hepatic duct tributaries received the same treatment and the malignancy was confirmed. No complications occurred. The prime indication for biopsy is to prove the presence of malignancy at this region and to provide an index for the management of cholangitis combined with choledocholithiasis.
THE MULTIPLICATION OF TUBERCLE BACILLI WITHIN NORMAL PHAGOCYTES IN TISSUE CULTURE
Authors: Emanuel Suter
Journal: The Journal of Experimental Medicine (1952)

A technique has been described for the cultivation in vitro of normal mononuclear cells on glass slides in a liquid medium. Under these conditions the monocytes transformed into macrophages which proliferated as in ordinary tissue culture. These cultures of monocytes could be infected with tubercle bacilli. The numbers of stainable tubercle bacilli within the monocytes increased steadily in cultures infected with virulent or attenuated strains. Evidence is given to support the view that this increase in numbers of bacilli was due to intracellular multiplication. There was no evidence of intracellular bacillary multiplication in cultures infected with an avirulent strain. Tubercle bacilli multiplying within phagocytes in vitro exert a damaging effect upon the host cells. The damage was most obvious in cells infected with a virulent strain. Tubercle bacilli within phagocytes were protected against the bacteriostatic effect of streptomycin added in a concentration of 5 gamma per ml. of culture medium. This permitted the use of streptomycin in infected cultures to prevent extracellular multiplication of the bacilli.
An Atlas of Head and Neck Surgery
Authors: Robert W. Cantrell
Journal: JAMA (1989)

The anatomy of the head and neck is the most complex in the body, encompassing all sense organs and a multiplicity of histological tissues. Wise surgeons contemplating surgery in this area approach it with respect. Added to the technical difficulties associated with the anatomy are cosmetic considerations. Unlike the rest of the body where surgical deformities are covered by clothes, the results of surgery on the head and neck are exposed for all to see. Owing to these considerations, a subspecialty of head and neck surgery began to develop nearly 50 years ago. Such surgeons as Conley, Jessee, Lewis, Martin, and Sisson contributed to the development of this field, and among head and neck surgeons, John M. Lore, Jr, occupies a special role. In addition to his clinical and academic contributions is this book, now in its third edition. It may be a bit costly at $135, but when considering
Roentgenographic Findings in Gardner's Syndrome
Authors: Fred M. H. Ziter
Journal: JAMA (1965)

THE ASSOCIATION of small intestinal polyps with characteristic pigmentation of the oral mucosa, lips, and digits (Peutz-Jeghers syndrome)1is a fairly well-known entity, but the association of true multiple colonic polyposis with other specific pathological findings is less well known. Although a few previous isolated reports had noted such an association, it remained for Gardner et al, in a series of articles from 1950 to 1953,2-5to bring to the attention of the medical profession the relationship between (1) familial multiple colonic polyposis, (2) multiple osteomatosis, and (3) various cutaneous and soft-tissue tumors. Since that time, the association of these disorders has been commonly referred to as Gardner's syndrome. The case reported below illustrates the roentgenographic findings in Gardner's syndrome.  Report of a Case  A 23-year-old single white salesman (204972) was seen at the surgical clinic. He first noticed a lump on the left side of his jaw
FAMILIAL HYPERCHOLESTEROLEMIA AND FEMORAL ATHEROSCLEROSIS: A META–ANALYSIS
Authors: Constantina Masoura, Konstantinos Aznaouridis, Pitsavos Christos, Skoumas Ioannis, Vlachopoulos Charalambos, Psarros Konstantinos, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2013)
Taxing “Sin Foods” — Obesity Prevention and Public Health Policy
Authors: Claudia Chaufan, Gee Hee Hong, Patrick Fox
Journal: New England Journal of Medicine (2009)

As the United States struggles to combat obesity, some health policy experts have asserted that a tax on sugar-sweetened beverages such as soda would lead to reduced consumption of sodas and increased consumption of more healthful beverages — and thus to healthier weights and important reductions in obesity-related health care costs.1 Although we find these assertions unwarranted, we would defend such a measure as an equitable way of tackling the obesity epidemic. Why wouldn't a soda tax decrease obesity rates by shifting consumption patterns toward healthier beverages? This is because price elasticity can refer to “own-elasticity” — changes in the . . .
Prognostic Value of Coronary Magnetic Resonance Angiography for Prediction of Cardiac Events in Patients With Suspected Coronary Artery Disease
Authors: Yeonyee E. Yoon, Kakuya Kitagawa, Shingo Kato, Masaki Ishida, Hiroshi Nakajima, Tairo Kurita, Masaaki Ito, Hajime Sakuma
Journal: Journal of the American College of Cardiology (2012)