tbuckley/cabot-search huggingface dataset:
Histamine and Mesenteric Artery Flow in the Dog
Authors: Arthur J. Madsen, Edward T. Peter, Demetre M. Nicoloff, Arnold I. Walder, Owen H. Wangensteen
Journal: JAMA (1963)

HISTAMINE has long been recognized as a vasoactive agent. Schayer<sup>1</sup>has recently presented data supporting the concept that histamine regulates the microcirculation under normal physiologic conditions independent of other nervous or humeral influences. Histamine appears to play a role in several pathologic conditions among them endotoxin and analphalactic shock as well as allergies of various kinds. The histamine gastric secretory test has been a fundamental, clinical, and research tool. While investigating the gastric blood flow response to histamine infusion,<sup>2</sup>the mesenteric artery blood flow was also determined and this forms the basis for this report. <h3>Method</h3> Mongrel dogs weighing from 10 to 12 kg (22 to 26.4 lb) were anesthetized with intravenous pentobarbitol. Blood pressure was monitored through a polyethylene catheter placed in the femoral artery connected to a stathum P<sup>23</sup>-AA strain gauge. Mesenteric artery flow was measured with a noncannulating gated electromagnetic flowmeter. Portal
Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract
Authors: Brian Becknell, Tad E. Eichler, Susana Beceiro, Birong Li, Robert S. Easterling, Ashley R. Carpenter, Cindy L. James, Kirk M. McHugh, David S. Hains, Santiago Partida-Sanchez, John D. Spencer
Journal: Kidney International (2014)
First do no harm with anti-obesity and other drugs
Authors: B. Toussaint
Journal: BMJ (2013)

<h3>Background</h3> <i>Rheumatoid arthritis</i> (RA) is a chronic, autoimmune, multisystemic, inflammatory and common disease with unknown etiology. <i>Cytochrome</i> P450 2C9 (CYP2C9) is responsible for up to 40 drugs metabolism in the liver such as oral anticoagulants (warfarin), oral antidiabetics (tolbutamide, glyburide), angiotensin II receptor antagonists (losartan, irbesartan), phenytoin (1). Most of the drugs convert to active or inactive metabolites by CYP2C9. In a recent study Goktas MT <i>et al</i>. showed that CYP2C9 activity reduced in Behçet9s disease that an autoimmune disease (2). <h3>Objectives</h3> This study aimed to investigate activity of CYP2C9 in patients with RA. <h3>Methods</h3> Losartan and its metabolite (E-3174) concentrations were analysed in healthy subjects (n=38) and RA patients (n=32) urine by high-performance liquid chromatography (HPLC). A acetonitrile and 66/34 mixture of phosphate tamponate (NaH2PO4, 15 mM, pH=2.8) were used as mobile phase. Urine samples in mobile phase and isopropanol (2/1/1 in volume, respectively) were injected into Agilent Eclipse XDB-C18 (5 μm, 4.6x150 mm) column via Agilent Technologies 1200 HPLC system (Agilent Technologies, Waldbron, Germany). Losartan and its metabolite E-3174 were detected via a UV detector at 245 nm. The inter- and intra-day coefficient of variation (CV) was less than %4 for losartan and its metabolite. The ratio of losartan to its metabolite (E-3174) was calculated (metabolic ratio, MR) and used as a marker of the activity of the CYP2C9 enzyme. <h3>Results</h3> MR (losartan/its metabolite ratio) was increased in RA patients from 1.34±0.22 to 1.75±0.31. This result shows that CYP2C9 activity decreased in RA patients compared with healthy subjects. <h3>Conclusions</h3> CYP2C9 activity decreased in RA patients so we must be carefully when using the drugs that metabolized with CYP2C9. The efficacy of some treatments would be compromised in RA patients because they were given drugs in dosages that might be ineffective or cause adverse drug reaction and toxicity. This study is continued at other centers. <h3>References</h3> Hatta FH, Teh LK, Helldén A, Hellgren KE, Roh HK, Salleh MZ, Aklillu E, Bertilsson L. Search for the molecular basis of ultra-rapid CYP2C9-catalysed metabolism: relationship between SNP IVS8–109A&gt;T and the losartan metabolism phenotype in Swedes. Eur J Clin Pharmacol. 2012;68(7):1033–42. Goktaş MT, Hatta F, Karaca O, Kalkisim S, Kilic L, Akdogan A, Babaoglu MO, Bozkurt A, Helldén A, Bertilsson L, Yasar U. Lower CYP2C9 activity in Turkish patients with Behçet9s disease compared to healthy subjects: a down-regulation due to inflammation? Eur J Clin Pharmacol. 2015;71(10):1223–8. <h3>Disclosure of Interest</h3> None declared
Pregnant women support extra screening test for Down's syndrome
Authors: Z. Kmietowicz
Journal: BMJ (2014)

A test that is 99% accurate in predicting the risk of Down’s syndrome and reduces the number of women who need invasive testing has the backing of pregnant women, early research has found.

Non-invasive prenatal testing (NIPT), which checks maternal blood for fetal DNA indicative of Down’s syndrome, has been available in private clinics in the United Kingdom for several years. The test also screens for the rarer genetic conditions Edward’s syndrome and Patau syndrome.

Early results from an acceptability trial among pregnant women in NHS maternity clinics have shown that most welcomed the opportunity to have another non-invasive test if they were found to be at high risk of carrying a fetus with Down’s syndrome on initial …
Stevens-Johnson Syndrome Associated With Long-Acting Sulfonamides
Authors: Oree M. Carroll
Journal: JAMA (1966)

THE STEVENS-JOHNSON syndrome (erythema multiforme exudativum; Behçet syndrome)<sup>1</sup>appears to be causally related to the use of the long-acting sulfonamides as well as other drugs and certain disease conditions.<sup>2,3</sup>In an attempt to clarify this association and to delineate the scope of the problem, the Bureau of Medicine of the Food and Drug Administration has surveyed reports from the medical literature, reviewed adverse drug reaction data from other sources in the files of the FDA, and consulted various experts in the field. This communication is a summary of the data obtained and outlines FDA actions on the long-acting sulfonamides. <h3>Background Considerations</h3> The first long-acting sulfonamide was introduced to American medicine in 1957. At the present time, sulfamethoxypyridazine and sulfadimethoxine are in wide clinical use. These drugs require as little as one oral dose every 24 hours to maintain adequate therapeutic levels, thus differing markedly from the short-acting congeners.
THE INTRATRACHEAL INJECTION OF OILS FOR DIAGNOSTIC AND THERAPEUTIC PURPOSES
Authors: H. J. CORPER
Journal: JAMA (1922)

Too frequently the haste occasioned by apparent clinical necessity leads to the introduction of diagnostic and therapeutic procedures without full scientific knowledge regarding the detailed action of such procedures on the body. It is this failure fully to test such procedures before employing them that leads to an abandonment of many forms of therapy recommended on the basis of strict clinical studies. From the enormous mass of material presented each year, a certain small portion of good may eventually be derived either, though rarely, through the employment of procedures in their complete form, as originally presented, or in a form decidedly restricted or limited by subsequent experience and study. Many attempts have been made to institute intrapulmonary types of therapy; but, thus far, all have led to uncertain success. Such attempts, in which category may be included the introduction of antiseptics into the lungs by inhalation, have uniformly proved not
Minimally modified low density lipoprotein is biologically active in vivo in mice.
Authors: F Liao, J A Berliner, M Mehrabian, M Navab, L L Demer, A J Lusis, A M Fogelman
Journal: Journal of Clinical Investigation (1991)

Minimally modified low density lipoprotein (MM-LDL), derived by mild iron oxidation or prolonged storage at 4 degrees C, has been shown to induce certain inflammatory responses in vascular cells in tissue culture. These include induction of monocyte (but not neutrophil) adherence to endothelial cells (EC), induction of EC production of colony stimulating factors (CSF), and induction of EC and smooth muscle cell production of monocyte chemotactic protein (MCP-1). To test for biologic activity in vivo, microgram quantities of MM-LDL were injected into mice, sera were assayed for CSF activity, and tissues were subjected to Northern analysis. After injection of MM-LDL, CSF activity increased approximately 7-26-fold but remained near control levels after injection of native LDL. Essentially all of the induced CSF activity was due to macrophage CSF as judged by antibody inhibition. Injection of MM-LDL into a mouse strain (C3H/HeJ) that is resistant to bacterial LPS gave similar results, indicating that the induction of CSF was not due to contaminating LPS and suggesting that there are differences in the pathways by which LPS and MM-LDL trigger cytokine production. In addition, after injection of MM-LDL, mRNA for JE, the mouse homologue of MCP-1, was markedly induced in various tissues, but was not induced after injection of native LDL. We conclude, therefore, that MM-LDL is biologically active in vivo and may contribute to the early stages of atherosclerosis by acting as an inflammatory agent.
Reply to Fabio Campodonico, Giacomo Capponi and Massimo Maffezzini’s Letter to the Editor re: Vincent Cloutier, Umberto Capitanio, Laurent Zini, et al. Thirty-Day Mortality after Nephrectomy: Clinical Implications for Informed Consent. Eur Urol 2009;56:998–1005
Authors: Claudio Jeldres, Pierre I. Karakiewicz
Journal: European Urology (2009)
Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.
Authors: M Gullberg, K A Smith
Journal: The Journal of Experimental Medicine (1986)

During the course of investigating the regulation of IL-2-dependent T cell proliferation, we found that the subset of human T cells expressing the T4 surface glycoprotein become refractory to IL-2 growth promotion earlier than T8+ cells. Since T4+ cells proliferate in an autocrine fashion to endogenous IL-2, whereas most T8+ cells respond in a paracrine fashion to IL-2 derived from T4+ cells, we thought it likely that a unique mechanism was operative to restrict T4+ cell IL-2-dependent autocrine proliferation. Moreover, we anticipated that the T4+ cell IL-2-refractory state related either to suppression by T8+ cells, or to expression of T4+ cell IL-2-R. However, several experimental approaches did not support either of these mechanisms as being responsible for the loss of T4+ cell IL-2 responsiveness. Isolated T4+ cells ceased to respond to IL-2 well before T8+ cells, and before the disappearance of adequate levels of IL-2-R. Moreover, a detailed comparison of IL-2-R expression by T4+ vs. T8+ cells revealed no differences in the number, affinity, rate of expression, or functional activity of high-affinity IL-2-R expressed by the two subsets. Accordingly, T4+ cell autocrine IL-2 responsiveness is restricted by a mechanism that is independent of IL-2-R, and which ultimately results in cessation of both T4+ and T8+ cell IL-2-dependent clonal expansion.
Cardiovascular pharmacology: Edited by W.W. Parmley, K. Chatterjee. 275 pp., 70.00 (hardback). Hong Kong: Mosby-Year Book Europe, Ltd, 1993. ISBN 1-56375-160-7
Authors: N. Flores
Journal: Cardiovascular Research (1995)

Cardiovascular pharmacology: Edited by W.W. Parmley, K. Chatterjee. 275 pp., £70.00 (hardback). Hong Kong: Mosby-Year Book Europe, Ltd, 1993. ISBN 1-56375-160-7 Get access Nick Flores Nick Flores London, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 2, August 1995, Page 313, https://doi.org/10.1016/S0008-6363(95)90132-9 Published: 01 August 1995
Abstract LB-343: Host response to paclitaxel chemotherapy promotes metastasis via the secretion of VEGF-C by macrophages.
Authors: Svetlana Gingis-Velitski, Orit Kaidar-Person, Dror Alishekevitz, Rotem Bril, Ella Fremder, Yuval Shaked
Journal: Cancer Research (2013)

Abstract Recent studies indicate that while chemotherapy can strongly restrict or reverse tumor growth, the response of the normal host tissue to the therapy can counteract tumor growth control by promoting the re-growth of residual tumor cells and the outgrowth of metastases. We sought for host factors promoting metastasis following paclitaxel (PTX) chemotherapy. The prolymphangiogenic growth factor, VEGF-C, was highly expressed in plasma of PTX-treated mice, and could induce migration, invasion, and tube formation of lymphatic vessels when compared to plasma from control mice. In both 4T1 breast and Lewis lung carcinomas we found an increased number of lymphatic vessels positioned at the center of the tumors from PTX-treated mice, in contrast to tumors from control mice, in which lymphatic vessels were positioned at the tumor periphery. Since VEGFR3 is the major receptor for VEGF-C-induced lymphangiogenesis, we evaluated the therapeutic effect of anti-VEGFR3 blocking antibody in combination with PTX. 4T1 bearing mice treated with PTX+anti-VEGFR3 exhibited a significant reduction in tumor re-growth and inhibition of metastasis which enhanced their overall survival, when compared to mice treated with PTX alone. However, no significant difference in survival of mice bearing 4T1 experimental metastasis in the lungs, was observed in any of the treatment groups, suggesting that VEGFR3 and VEGF-C promote tumor cell dissemination from treated tumors, but may not affect their seeding at metastatic sites. In addition, an abundant number of macrophages highly secreting VEGF-C were found to colonize 4T1 tumors from PTX-treated mice when compared to tumors from untreated mice. Similarly, breast carcinomas from cancer patients after neoadjuvant chemotherapy exhibited high expression of VEGF-C when compared to their pre-treated biopsies. Overall, our results suggest an additional role for macrophages in the tumor microenvironment, which in response to chemotherapy promote tumor re-growth and metastasis spread, a process which can be blocked by the disruption of VEGF-C/VEGF-R3 pathway. Citation Format: Svetlana Gingis-Velitski, Orit Kaidar-Person, Dror Alishekevitz, Rotem Bril, Ella Fremder, Yuval Shaked. Host response to paclitaxel chemotherapy promotes metastasis via the secretion of VEGF-C by macrophages. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-343. doi:10.1158/1538-7445.AM2013-LB-343
3D Image Reconstruction of Histopathological Structure of Atherosclerotic Plaque Using a Novel Technique With Film Tomography
Authors: Takafumi Hiro, Tadateru Takayama, Hironori Haruta, Masayuki Mitsumori, Kimio Tanaka, Junichi Kawanabe, Sumihare Noji, Atsushi Hirayama
Journal: JACC. Cardiovascular imaging (2014)
ANTIBODY FORMATION
Authors: Jonathan W. Uhr, Martin S. Finkelstein
Journal: The Journal of Experimental Medicine (1963)

Injection of a sufficient dose of bacteriophage ϕX 174 into guinea pigs results in the formation of rapidly sedimenting antibody molecules (19S), and later, slowly sedimenting molecules (7S). Above a threshold dose of antigen, the relative rate of 19S formation is maximal and dose-independent; below this dose, slower relative rates are obtained. The time for doubling the serum 19S level is as short as 6 to 8 hours, suggesting that the absolute rate of antibody formation per cell is increasing in addition to proliferation of antibody-producing cells. Synthesis of 19S after injection of 1010 ϕX virtually ceases at 10 days after which 19S antibody activity disappears from the circulation with a half-life of approximately 24 hours. A second injection of ϕX on day 5 or 9 prolongs 19S synthesis, indicating that antigen not only can regulate the relative rate, but also is essential for continued synthesis of 19S. 19S synthesis is also prolonged in guinea pigs by injection of ϕX with endotoxin or by 400 r whole body x-irradiation 24 hours after injection of phage into rabbits. The primary 7S response is not detected until approximately 1 week after immunization and relative rates are antigen-dependent. Primary 7S synthesis can continue for many months and leads to preparation for a secondary antibody response (immunological memory) during which only 7S is detected. In contrast, in animals that form precipitating 19S without detectable 7S, a second injection of phage 1 month later results in a second 19S response which closely resembles the first. These findings have led to the suggestion that formation of 19S does not lead to persisting immunological memory.
Reye's syndrome: Are adults big children?
Authors: Patricia S. Latham
Journal: Hepatology (1988)

Reye’s syndrome (RS) is generally considered a childhood disease. We report our experience with RS in adults in the metropolitan Milwaukee area. Reye’s syndrome was diagnosed in seven 18- to 46-year-old adults. The diagnostic criteria were as follows: viral prodrome followed by vomiting and encephalopathy without focal neurological signs, normal cerebrospinal fluid values, increased levels of serum aminotransferases (transaminase), prolonged prothrombin time, elevated blood ammonia levels, and characteristic microvesicular fatty liver and mitochondrial changes. None of the patients was hypoglycemic. The diagnosis of RS was entertained in 22 but confirmed in only seven patients. In cases of non-Reye’s encephalopathy, drug ingestion presented as one of the most difficult differential diagnostic problems, which also included alcohol abuse, collagen vascular disease, and hepatitis B surface antigenemia. Clinical jaundice, distinctly uncommon in RS, was present in only one patient who presented to us in stage V coma. In adults, RS is more difficult to diagnose and should be suspected more frequently in patients with unexplained altered behavior following a viral illness and vomiting. Liver biopsy can be performed safely and is usually mandatory in adults. Patients with RS diagnosed during stage I or II coma and treated experienced an uneventful recovery.
Low-T3 Syndrome
Authors: Giorgio Iervasi, Alessandro Pingitore, Patrizia Landi, Mauro Raciti, Andrea Ripoli, Maria Scarlattini, Antonio L’Abbate, Luigi Donato
Journal: Circulation (2003)

Background— Clinical and experimental data have suggested a potential negative impact of low-T3 state on the prognosis of cardiac diseases. The aim of the present prospective study was to assess the role of thyroid hormones in the prognosis of patient population with heart disease. Methods and Results— A total of 573 consecutive cardiac patients underwent thyroid function profile evaluation. They were divided in two subgroups: group I, 173 patients with low T3, ie, with free T3 (fT3) &lt;3.1 pmol/L, and group II, 400 patients with normal fT3 (≥3.1 pmol/L). We considered cumulative and cardiac death events. During the 1-year follow-up, there were 25 cumulative deaths in group I and 12 in group II (14.4% versus 3%, P &lt;0.0001); cardiac deaths were 13 in group I and 6 in group II (7.5% versus 1.5%, P =0.0006). According to the Cox model, fT3 was the most important predictor of cumulative death (hazard ratio [HR] 3.582, P &lt;0.0001), followed by dyslipidemia (HR 2.955, P =0.023), age (HR 1.051, P &lt;0.005), and left ventricular ejection fraction (HR 1.037, P =0.006). At the logistic multivariate analysis, fT3 was the highest independent predictor of death (HR 0.395, P =0.003). A prevalence of low fT3 levels was found in patients with NYHA class III-IV illness compared with patients with NYHA class I-II (χ 2 5.65, P =0.019). Conclusions— Low-T3 syndrome is a strong predictor of death in cardiac patients and might be directly implicated in the poor prognosis of cardiac patients.
A Medical Version of the Faust Legend
Authors: Marjorie C. Meehan
Journal: JAMA (1966)

Although the legend of Faust, the scholar who sold his soul to the devil, has been a popular subject for literary works since the 16th century, it was not until mid-20th century that a medical interpretation was given to the story. Previous writers had portrayed the devil as an actual personification of evil or as an imaginary symbolic character. They made no attempt to interpret Faust's behavior in psychiatric terms. Thomas Mann, the German novelist, in his<i>Doctor Faustus</i>, showed the devil as imaginary or hallucinatory, but the pact with him as real, in that the protagonist willingly accepted syphilis of the central nervous system as a means to greater artistic creative power. <h3>Early Versions</h3> Dr. Johannes Faustus was evidently a real individual who lived in the 15th and early 16th centuries, about whom many odd stories were told. Between 1570 and 1587, these were gathered in manuscript form, and
The Late Appearance of Postpartum Eclampsia
Authors: Erol Amon
Journal: JAMA (1986)

To the Editor.—  While we are glad that Dr Michaeli 1 has recognized the phenomenon of late postpartum eclampsia, it is not as unusual as indicated by the reporting of his case. We have managed two such cases, occurring on days 4 and 6 after delivery, in the past two weeks.  The entity of late-appearing postpartum eclampsia is clouded with confusion and controversy. As early as 1946, Stander and co-workers 2 reported the possibility that eclampsia can and does occur beyond 72 hours after delivery. There are authors who have clearly reported cases of postpartum eclampsia, documented by renal biopsy specimens and postmortem examination, 3-5 occurring three to 23 days after delivery. Other authors state that the majority of cases occur within the first 24 hours after delivery, with a small number of cases occurring on the second day after delivery and a progressively smaller incidence thereafter.  The most recent
A male with primary breast lymphoma
Authors: Yasuo Miura, Masatoshi Nishizawa, Hitomi Kaneko, Mitsumasa Watanabe, Mitsuru Tsudo
Journal: American Journal of Hematology (2008)

A 64-year-old man was referred to our hospital with a history of painless, gradually growing lump in his left breast.On physical examination, nontender, irregular surface, demarcated elastic firm tumor (6 cm 3 7 cm in size) was palpable in the medial area of his left breast (Image 1A).Fine needle aspiration cytology of the tumor cells showed that lymphocytic cells with prominent nucleoli were dispersed as single cells (Image 1B).Microscopic examination of the tumor with core needle biopsy (CNB) confirmed diffuse proliferation of CD20-positive large atypical lymphocytes (Image 1C,D).A magnetic resonance imaging (MRI) examination showed a lobulated, well-demarcated breast tumor of high-intensity in T2-weighted fat-saturated image (T2WI F-SAT, Image 1E) and of isointensity in T1-weighted image (T1WI) to the adjacent muscles (Image 1F).The breast tumor was diagnosed with non-Hodgkin lymphoma, classified as diffuse large B-cell lymphoma.Blood examination was normal including serum lactate dehydrogenase and soluble interleukin-2 receptor.There was no evidence of lymphoma involvement in bone marrow and cerebrospinal fluid.A [ 18 F]-fluorodeoxyglusoce (FDG) positron emission tomography/computed tomography (PET/ Image 1. (A) Appearance of breast lump (blue arrows).Histological findings of the breast tumors, (B) Papanicolou stain shows dispersed lymphocytic cells with prominent nucleoli, (C) HE stain shows diffuse proliferation of large atypical lymphocytes, and (D) the atypical lymphocytes are positive for CD20, a B-cell marker, confirmed by the immunohistochemical analysis.(E-J) Radiological findings of the breast tumors.A lobulated, well-demarcated, high-intensity tumor in T2-weighted fat-saturated image (T2WI F-SAT) of MRI before the treatment (E, blue arrow) is disappeared after six cycles of chemotherapy (J).(F) The breast tumor with iso-intensity to the adjacent muscle in T1-weighted image (T1WI) of MRI before the treatment (blue arrow).A PET/CT demonstrates increased focal FDG uptake in the breast tumor before treatment (G and H, blue arrow) whereas no FDG uptake is observed after the chemotherapy (I).