tbuckley/cabot-search huggingface dataset:
Vascular Endothelial Growth Factor Reduces Tamoxifen Efficacy and Promotes Metastatic Colonization and Desmoplasia in Breast Tumors
Authors: Zhican Qu, Sabrina Van Ginkel, Anshu M. Roy, Louise Westbrook, Mubina Nasrin, Yulia Maxuitenko, Andra R. Frost, Delicia Carey, Wenquan Wang, Rongbao Li, William E. Grizzle, Jaideep V. Thottassery, Francis G. Kern
Journal: Cancer Research (2008)

Abstract Clinical studies have shown that decreased tamoxifen effectiveness correlates with elevated levels of vascular endothelial growth factor (VEGF)-A165 in biopsy samples of breast cancers. To investigate the mechanisms underlying tamoxifen resistance and metastasis, we engineered the estrogen receptor (ER)–positive MCF-7 human breast cancer cell line to express VEGF to clinically relevant levels in a doxycycline-regulated manner. Induction of VEGF expression in orthotopically implanted xenografts that were initially tamoxifen responsive and noninvasive resulted in tamoxifen-resistant tumor growth and metastasis to the lungs. Lung metastases were also observed in a VEGF-dependent manner following tail vein injection of tumor cells. At both primary and metastatic sites, VEGF-overexpressing tumors exhibited extensive fibroblastic stromal content, a clinical feature called desmoplasia. VEGF-induced metastatic colonies were surrounded by densely packed stromal cells before detectable angiogenesis, suggesting that VEGF is involved in the initiation of desmoplasia. Because expression of VEGF receptors R1 and R2 was undetectable in these tumor cells, the observed VEGF effects on reduction of tamoxifen efficacy and metastatic colonization are most likely mediated by paracrine signaling that enhances tumor/stromal cell interactions and increases the level of desmoplasia. This study reveals new roles for VEGF in breast cancer progression and suggests that combination of antiestrogens and VEGF inhibitors may prolong tamoxifen sensitivity and prevent metastasis in patients with ER-positive tumors. [Cancer Res 2008;68(15):6232–40]
Effects of the site and timing of atrioventricular nodal input on atrioventricular conduction in the isolated perfused rabbit heart.
Authors: T Mazgalev, L S Dreifus, H Ininuma, E L Michelson
Journal: Circulation (1984)

Programmed stimulation was used to study patterns of atrioventricular nodal propagation in an isolated rabbit heart preparation. Stimulation was done at the two major atrioventricular nodal input regions, the crista terminalis and interatrial septum, by use of various sequencing protocols. The influence of stimulation input interactions on atrioventricular nodal propagation was then evaluated with the use of simultaneous extracellular and intracellular recordings from the various regions of the atrioventricular node and His bundle. Activation of the atrioventricular node occurred predominantly via the stimulated input site, although perinodal conduction to the opposite input also occurred and could modify the atrioventricular conduction pattern. Engagement patterns of both AN and N fibers were dependent on the sequence of activation at the major input sites, and similar conduction times to the His bundle were often associated with different local activation times, depending on the site of premature stimulation. Conversely, if premature stimulation was timed to produce constant local activation times but the input site varied, then the time to His bundle activation could also vary. Atrioventricular nodal functional and effective refractory periods and conduction patterns were dependent on both the timing and pattern of engagement at the principal inputs to the atrioventricular node as well as the subsequent organization of activation of the various regions of the atrioventricular node. Furthermore, depending on the sequence of stimulation at the crista terminalis and interatrial septum, activation patterns were either organized or inhomogeneous in the AN and N regions of the atrioventricular node, consequently influencing the H-H interval, and in some instances resulting in conduction block to the His bundle. It is concluded that the relative timing of activation at the principal input regions of the atrioventricular node is critical to patterns of atrioventricular nodal propagation and subsequent conduction to the His bundle. Our results emphasize the complexity of atrioventricular nodal propagation during premature stimulation.
Mutation analysis of hepcidin and ferroportin genes in Italian prospective blood donors with iron overload
Authors: Lorena Duca, Paola Delbini, Isabella Nava, Valentina Vaja, Gemino Fiorelli, Maria Domenica Cappellini
Journal: American Journal of Hematology (2009)

Maintenance of iron balance is essential for humans and requires the coordinate regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. Hepcidin, a recently identified antimicrobial peptide produced in the liver, has been shown to play a central role in the homeostatic regulation of iron absorption and distribution [1]. It is a negative regulator of iron absorption in the small intestine and of iron release from macrophages engaged in the recycling of iron senescent erythrocytes [2]. The human hepcidin gene contains three exons that encode a 72-aa precursor (pro-hepcidin) with a characteristic furin cleavage site immediately N-terminal to the 25-aa major hepcidin species found in plasma and urine [3]. Recently, hepcidin has been shown to regulate iron homeostasis by interaction with ferroportin, an iron cellular exporter highly expressed in absorptive enterocytes, macrophages, hepatocytes, and placental cells [4].
Impact of Banning Alcohol on Outpatient Visits in Barrow, Alaska
Authors: Arva Y. Chiu
Journal: JAMA (1997)

<h3>Context.</h3> —Community availability of alcohol affects alcohol consumption patterns and alcohol-related health and social problems. In Barrow, Alaska, an isolated community at the northernmost reaches of the United States, during a 33-month period, possession and importation of alcohol were legal, completely banned, made legal again, and then banned again. <h3>Objective.</h3> —To determine the impact of these public policy changes on alcohol-related outpatient visits at the area hospital. <h3>Design.</h3> —Retrospective review of outpatient records; time-series analysis of alcohol-related visits with respect to community alcohol policy. <h3>Main Outcome Measures.</h3> —Total monthly outpatient visits for alcohol-related problems. <h3>Results.</h3> —There was a substantial decrease in the number of alcohol-related outpatient visits when the ban on possession and importation was imposed compared with baseline. When the ban was lifted, outpatient visits increased; when the ban was reimposed, the number of outpatient visits again decreased. Interrupted time-series analyses confirm that the alcohol ban, its lifting, and its reimposition had a statistically significant and negative effect on the number of alcohol-related out-patient visits (<i>P</i>&lt;.05). <h3>Conclusion.</h3> —In a geographically isolated community, the prohibition of alcohol can be an effective public health intervention, reducing the health problems associated with alcohol use.
Indications and Contraindications
Authors: Richard S. Handley
Journal: JAMA (1967)

There are no absolute and invariable rules for the treatment of any form of carcinoma in an individual. The general physical state, the psychological stability, and the social circumstances may all modify the accepted treatment for a particular form of malignancy, and what follows concerning the indications and contraindications for mastectomy in stage III carcinoma of the breast is written in the knowledge that there are circumstances under which the advice given must be modified or even disregarded. It is necessary first to consider what we are talking about when we speak of a stage III carcinoma of the breast. First, we are here concerned with clinical staging, as distinct from the more accurate pathologic staging which can only be achieved by hindsight in the light of the histologist's report and which is not, therefore, available when decisions about treatment have to be made. Second, clinical staging is bedeviled by
Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis
Authors: D. CREAMER, M.H. ALLEN, A. SOUSA, R. POSTON, J.N.W.N. BARKER
Journal: British Journal of Dermatology (1997)

Journal Article Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis Get access D. CREAMER, D. CREAMER St John's Institute of Dermatology, UMDS, St Thomas Hospital Campus, London SE1,7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.H. ALLEN, M.H. ALLEN St John's Institute of Dermatology, UMDS, St Thomas Hospital Campus, London SE1,7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. SOUSA, A. SOUSA Departments of Dermatology UMDS, St Thomas Hospital Campus, London SE1,7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. POSTON, R. POSTON Departments of Experimental Pathology. UMDS. Guy's Hospital Campus, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.N.W.N. BARKER J.N.W.N. BARKER St John's Institute of Dermatology, UMDS, St Thomas Hospital Campus, London SE1,7EH, U.K. Dr J.Barker, St John's Institute of Dermatology, St Thomas' Hospital. Lambeth Palace Road, London SEI 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 6, 1 June 1997, Pages 859–865, https://doi.org/10.1046/j.1365-2133.1997.01845.x Published: 01 June 1997 Article history Accepted: 08 January 1997 Published: 01 June 1997
Complete Local Elimination of Infectious Trachoma from Severely Affected Communities after Six Biannual Mass Azithromycin Distributions
Authors: Jesse B. Biebesheimer, Jenafir House, Kevin Cyrus Hong, Takele Lakew, Wondu Alemayehu, Zhaoxia Zhou, Jeanne Moncada, Andrew Rogér, Jeremy Keenan, Bruce D. Gaynor
Journal: Ophthalmology (2009)
Periodic Skin Eruptions
Authors: Hobart A. Reimann
Journal: JAMA (1964)

<h3>To the Editor:—</h3> I the Question and Answer, "Skin Lesions of Mouth, Throat, and Genitalia" (<i>JAMA</i><b>188</b>: 836 [June 1] 1964), the consultant states that, "The history does not indicate whether or not... a consistent relationship between exposures [to noxious gases] and attacks exists." True, nor does the history tell if the episodes started before or after the patient became a welder. Should sensitivity to some chemical not be the cause, there are other possibilities. If the "periodic" mucosal and dermal lesions recur with precise three-week or other regularity, two disorders may be considered: periodic aphthous stomatitis and periodic myelodysplasia if synchronous neutropenia occurs (<i>Blood</i><b>6</b>:1109, 1949). A "bacteriotoxic etiology" and especially "foci of infection" are unlikely.
Monitoring and Evaluating Progress towards Universal Health Coverage in Ethiopia
Authors: Abebe Alebachew, Laurel Hatt, Matthew Kukla
Journal: PLoS Medicine (2014)

This paper is a country case study for the Universal Health Coverage Collection, organized by WHO. Abebe Alebachew and colleagues illustrate progress towards UHC and its monitoring and evaluation in Ethiopia. Please see later in the article for the Editors' Summary
Isolated Congenital Complete Atrioventricular Block in Adult Life
Authors: Magnus Michaëlsson, Anders Jonzon, Tomas Riesenfeld
Journal: Circulation (1995)

The prognosis of congenital complete atrioventricular block (CCHB) is usually considered favorable in adults. This belief is based on studies comprising a limited number of patients and with rather short observation times. In the present study, the natural history of the disease was investigated by a prospective follow-up through decades of adult life of patients with a large group having well-defined CCHB without structural heart disease.The diagnostic criteria of CCHB proposed by Yater were applied. Patients registered as having CCHB in 1964, supplemented by younger patients all without symptoms during their first 15 years of life, were selected. The study was limited to patients with isolated, complete, permanent block. An interview was conducted with all patients and clinical follow-up data obtained. There were finally 102 patients, 61 women and 41 men. In November 1994, the time of observation, after the age of 15 years in survivors, was between 7 and 30 years. The mean age at follow-up or at death was 38 years, median age 37 years, and range 16 to 66 years. Stokes-Adams (SA) attacks occurred in 27 patients, in 8 with a fatal outcome. The first attack was fatal in 6 of these 8 patients. Nineteen survived and a pacemaker (PM) was implanted thereafter. Another 8 patients received a PM because of repeated fainting spells, and 27 others have had a PM implanted for other reasons such as fatigue, effort dyspnea, dizziness, ectopies during exercise tests, mitral regurgitation, and a low ventricular rate (VR). VR decreased with age, with a mean rate at 15 years of 46 beats per minute (bpm), at 16 to 20 years of 43 bpm, at 21 to 30 years of 41 bpm, at 31 to 40 years of 40 bpm, and after 40 years of age of 39 bpm. SA attacks occurred in all 7 patients with prolonged QTc time. Low VR at rest or at work, presence of bundle-branch block pattern, low working capacity, and ectopies at rest and/or during effort were not statistically significant risk factors. SA attacks occurred in 6 patients without any of these signs. Mitral regurgitation developed in 16 patients and 4 died. A PM reduced the risk of death. A change to a lower degree of block occurred in 6 patients.Prophylactic PM treatment is recommended even for symptom-free adults with CCHB because of the high incidence of unpredictable SA attacks with considerable mortality from first attacks, a gradually decreasing VR, significant morbidity, and a high incidence of "acquired" mitral insufficiency.
Relation Between Muscle Contraction Speed and Hydraulic Performance in Skeletal Muscle Ventricles
Authors: Jonathan C. Jarvis, Martin M.N. Kwende, Adam Shortland, Reida M. Eloakley, Stephen J. Gilroy, Richard A. Black, Stanley Salmons
Journal: Circulation (1997)

Background The fatigue resistance and power-to-weight ratio of skeletal muscle that has been conditioned by electrical stimulation makes cardiac assistance from a graft of such muscle a realistic prospect. A skeletal muscle must be surgically reconfigured to act on the circulating blood, but little is known about the power losses that accompany such interventions. We investigated in acute experiments the hydraulic performance of approximately cylindrical pumps made from sheep latissimus dorsi (LD) muscles, having first characterized the performance of each muscle in situ. Methods and Results Force-length and force-velocity relations were measured in situ for LD that had received either 8 weeks of stimulation at 2 Hz or no chronic stimulation. Two sizes of skeletal muscle ventricle (SMV) were formed from the same muscles, and their hydraulic performance was measured. The hydraulic performance was also calculated from the linear data, models of the force-length and force-velocity curves, and a description of the stress distribution within the SMV wall. The model predicted well the isovolumetric function of the ventricles and the optimum afterload but overestimated the flow and therefore the power. In conditioned ventricles the performance was particularly poor because of the slow contractile properties of the muscles. Conclusions If SMVs are to pump effectively against the arterial impedance, the pressure drop caused by flow (or the internal resistance) should be lower than that of the ventricles we constructed. Progress can be made through refinement of surgical technique and stimulation protocols that generate faster fatigue-resistant muscles.
Antibodies to Hepatitis B Surface Antigen as the Sole Hepatitis B Marker in Hospital Personnel
Authors: HAROLD A. KESSLER
Journal: Annals of Internal Medicine (1985)

The epidemiologic and serologic differences between hospital employees with antibodies to hepatitis B surface antigen (anti-HBs) alone or in combination with antibodies to hepatitis B core antigen (anti-HBc) were evaluated. Of 105 employees with anti-HBs, 38 (36%) did not have anti-HBc. Sera from employees with anti-HBs alone had significantly lower mean sample ratio units of anti-HBs than sera with both antibodies (15.9 ± 43.2 as compared to 110.3 ± 73.9, p < 0.0005) and more commonly had less than 10 sample ratio units of anti-HBs (32 [84%] of 38 as compared to 9 [13%] of 67, p = 0.0001). The anti-HBs in sera with anti-HBs alone was predominantly IgM as shown by inactivation with 2-mercaptoethanol and the presence of anti-HBs activity in serum IgM fractions. Failure of protection from hepatitis B virus infection in persons with anti-HBs alone and the presence of nonprotective IgM anti-HBs in chimpanzees has been reported. Our data suggest the use of anti-HBs as a single serologic screening test for hepatitis B virus immunization programs may not be reliable in identifying employees with protective antibodies.
Human Disease in Color
Authors: Charles B. Clayman
Journal: JAMA (1979)

Dr Smith has assembled full-color photographs of gross and microscopic specimens representing 140 different diseases of several of the organ systems of the body. To these he has added succinct case reports providing symptoms and findings as well as some of the natural history of the conditions presented. These reports and a comment regarding the pathological material are arranged to immediately precede or follow the photographs. The book is organized so each system is introduced with a description of a normal organ (heart, lung, brain, kidney, thyroid, and adrenal gland) and then is followed with clinical examples of infarction, inflammation, degenerative disease, neoplasia, and miscellaneous entities. Descriptions of the gross material are excellent, but the briefer discussions of the histopathological appearance could be expanded. A larger page format would have permitted greater clarity of some of the gross specimens, but more important the photomicrographs would then have been able to
FIBRO-LIPOMA OF THE PHARYNX.Read in the Section on Laryngology and Otology at the Forty-fifth Annual Meeting of the American Medical Association held at San Francisco, June 5-8, 1894.
Authors: JOHN O. ROE
Journal: JAMA (1894)

REPORT OF CASE. Benign tumors of the oro-pharynx, involving the posterior wall alone, are of comparatively infrequent occurrence. Judging from the cases reported, and from my own experience, lipomatous tumors located in this region are the rarest of all. The following exceedingly interesting case, that of a large fibro-lipoma of the pharynx came under my observation last January, and is quite worthy of record: Mrs. R., 49 years of age, began nine months before I saw her to experience a sensation of roughness and fullness in her throat, attended with difficulty in swallowing, and associated with pain extending to both ears. While remaining quiet she experienced no special discomfort in her throat, but on attempting to swallow, the sensation of constriction about the throat and the pain in her ears would be frequently quite severe. This difficulty in swallowing began with the taking of solids, particularly in large pieces, and
Treatment for the Disuse Phenomenon-Reply
Authors: Victor G. deWolfe
Journal: JAMA (1964)

While I agree that sympathectomy should be reserved for those patients who fail to respond to an adequate program of intensive physical therapy and lumbar sympathetic blocks, as was the case in all of our patients who underwent sympathectomy, I cannot agree that orthostatic hypotension constitutes a significant complication of lumbar sympathectomy. Over a thousand lumbar sympathectomies have been done in this institution for peripheral vascular disorders, many of them in older patients with severe arteriosclerosis obliterans with hypertension, and I cannot recall a single case of significant orthostatic hypotension. I do not believe that the limited type of sympathectomy which is done to produce peripheral vasodilatation, consisting of unilateral removal of the third, fourth, and fifth or fourth and fifth lumbar ganglia, produces orthostatic hypotension, except perhaps in rare instances. On the other hand, extensive sympathectomy, such as the bilateral dorsolumbar sympathectomy advocated by Smithwick for hypertension, does indeed
Long-Acting Sulfonamides in Urinary Tract Infections
Authors: Harry Seneca
Journal: JAMA (1966)

The pharmacological properties, side effects and clinical indications of five long-acting sulfonamides are compared and their relative clinical efficacy evaluated. Their adequate and sustained tissue-blood levels due to slow excretion rates, at low dosages, make them valuable and safe suppressive antibacterial drugs in the management of chronic urinary tract infections. In acute infections, and if obstructive uropathy, hematological abnormalities, hepatic or renal dysfunction co-exist, they are not indicated. In our experience, sulfadimethoxine has been safe and efficacious. Sulfamethoxypyridazine, although effective, is too toxic for general use. Under clinical investigation are AHR-857 used in 197 patients, sulfalene in 43 patients, and Ro 4-4393 in 12 patients. Ro 4-4393 is extremely long acting; 1 gm weekly maintains effective blood levels for seven days. These three drugs have been clinically quite effective and safe.
THE TECHNIC OF BRONCHOGRAPHY AND A SYSTEM OF BRONCHIAL NOMENCLATURE
Authors: RALPH ADAMS
Journal: JAMA (1942)

As refinements in the technic of pulmonary resection have lowered mortality and morbidity rates, the medical profession and the group of patients symptomatically concerned have become increasingly interested in the possibility of relief from cough or sputum and the number of cases requiring critical evaluation has risen sharply.  Bronchography, as roentgen demonstration of the bronchial pattern by opaque mediums is called, is an essential diagnostic aid in the investigation of many such patients, and the use of the procedure has become widespread during recent years. Commendable as is the enthusiastic study of patients with a cough by all measures likely to discover its cause, the general use of iodized oil injection has raised certain problems. Numerous patients have been seen in consultation in whom a diagnosis of bronchiectasis has been established elsewhere by demonstrating iodized oil filling one or more grossly dilated bronchi in one or more lower lobes. The