tbuckley/cabot-search huggingface dataset:
PWE-104 Vitamin D in Inflammatory Bowel Disease. A Semi-Qualitative Assessment of the Patient Experience
Authors: M S Mohammad, J Mayberry
Journal: Gut (2013)

<h3>Introduction</h3> Vitamin D plays a vital role in bone health, immune regulation and cancer prevention in inflammatory bowel disease (IBD). Our understanding has increased remarkably in the past decade, although the mechanism of its influence in IBD remains unclear as does its role in treatment. Although the efficacy of vitamin D as an immunomodulator remains to be established, given current evidence it appears reasonable to screen and treat vitamin D deficiency in patients with IBD. <h3>Methods</h3> Two hundred consecutive patients with vitamin D deficiency were identified from IBD clinics at Leicester General Hospital who had been seen during a 12 month period. A postal questionnaire was sent to these patients. It was anonymous and requested whether: Respondents believed they had been told of their vitamin D deficiency. General practitioners had prescribed vitamin D supplements. Vitamin D supplements had been bought at local pharmacies. Brand of vitamin D supplements taken. Compliance with treatment. Symptoms had improved with treatment. They had enough sunlight exposure <h3>Results</h3> Ninety eight of the 200 patients responded to the questionnaire, a reponse rate of 49%. Sixty five were English and 33 Asian. The response rate was 48% in Asians and 50% in English which is not significantly different. Seventy (71%) of the 98 patients, recalled being told they were vitamin D deficient. Thirty nine patients (40%) believed they had sufficient exposure to sunlight. 54 (71%) had been prescribed this medication by general practitioners and 22 (29%) had bought vitamin D supplements over the counter at local pharmacies or herbal stores. General practitioners predominantly prescribed Adcal D3 tablets. Sixty four (84%) patients said they were adherent to vitamin D treatment. Symptoms improved significantly in 29 (38%) patients. However, this figure rose to 45% when only those 64 patients who were compliant with therapy were considered. <h3>Conclusion</h3> Vitamin D plays a significant role in intracellular functions which extends beyond its effects on bone metabolism. It is an important regulator of the immune system which may have implications for the development, severity and management of immune related disorders such as IBD. In summary the relationship between the vitamin D axis and IBD is multifaceted. It should comprise maintainence of musculoskeletal health and control of disease through immunomodulation and modification of associated malignancy. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Vitamin D and inflammatory bowel disease – established concepts and future directions Alimentary Pharmacology and Therapeutics (2012) 36, 324–344 M.Garg, J.S.Lubel, M.P.Sparrow, S.G. Holt &amp; P.R. Gibson 2. Vitamin D as a therapy for colitis A systematic review Journal of Crohns &amp; Colitis (2012) 6, 405–411 I Nicholson, A. Mark Dalzell, Wael El-Matary.
The Reno-Protective Effect of Hydration With Sodium Bicarbonate Plus N-Acetylcysteine in Patients Undergoing Emergency Percutaneous Coronary Intervention
Authors: Alejandro Recio-Mayoral, Marinela Chaparro, Belén Prado, Rocío Cózar, Irene Méndez, Debasish Banerjee, Juan C. Kaski, José Cubero, Jose M. Cruz
Journal: Journal of the American College of Cardiology (2007)
GPs feel pressurised to prescribe unnecessary antibiotics, survey finds
Authors: A. Cole
Journal: BMJ (2014)

Many GPs feel under pressure to prescribe antibiotics even when they may not be the correct treatment, and some patients continue to expect antibiotics as a matter of right, two parallel surveys from the Longitude Prize charity have found.

The surveys of more than 1000 GPs and a similar number of patients were commissioned by Nesta, the organisation behind the £10m (€12.5m; $16.6m) Longitude Prize, which the public voted to award to finding smarter ways of using existing antibiotics, in the face of growing resistance and a dearth of new types.1

The survey of GPs found that 55% felt under pressure—mainly from patients—to prescribe antibiotics, even …
Protein microarrays identify antibodies to protein kinase Cζ that are associated with a greater risk of allograft loss in pediatric renal transplant recipients
Authors: Scott M. Sutherland, Li Li, Tara K. Sigdel, Persis P. Wadia, David B. Miklos, Atul J. Butte, Minnie M. Sarwal
Journal: Kidney International (2009)
Abstract 1733: Therapeutic significance of ERα—PELP1 axis in blocking endocrine therapy resistance
Authors: Valerie A. Cortez, Takayoshi Suzuki, Naoki Miyat, Anil K. Sood, Ratna K. Vadlamudi
Journal: Cancer Research (2011)

Abstract Breast cancer therapies target the estrogen receptor-alpha (ERα) with letrozol an aromatase inhibitor or anti-estrogens such tamoxifen to limit circulating estrogen levels and alter ERα functions. Many women suffering from recurrent or advanced disease develop resistance to current targeted endocrine treatments. Emerging data suggests therapeutic resistance is precipitated through dysfunction of ERα coregulatory proteins and crosstalk between ERα and growth factor signaling. Deregulated expression of proline-, glutamic acid- and leucine-rich protein 1 (PELP1), an ERα coregulator, was observed in a subset of human breast tumors. Recently, PELP1 was identified as an independent prognostic biomarker of shorter survival in ERα positive/luminal-like breast cancer patients. Epigenetic changes of target gene promoters are modulated by PELP1 via an interaction with lysine specific demethylase 1 (KDM1). Additionally, PELP1 promotes crosstalk between ERα and Src kinase leading to enhanced activation of extranuclear signaling pathways. Therapeutic potential of targeting the ERα-PELP1 axis in vivo was examined using a pharmacological approach in well-established preclinical models of endocrine therapy resistant breast cancer. We utilized (1) siRNA liposomes to down regulate PELP1 expression; (2) pargyline and NCL-1, KDM1 inhibitors, to block PELP1-mediated epigenetic modifications and (3) dasatinib, a Src kinase inhibitor, to prevent PELP1-mediated extranuclear actions in both pre- and post-menopausal conditions. In xenograft-based assays, treatment of ERα positive breast cancer cells with liposomes containing PELP1-siRNA, dasatinib or KDM1 inhibitors significantly reduced proliferation and tumor growth. Combinatorial therapies of letrozol or tamoxifen with PELP1 axis blockers substantially impeded xenograft tumor growth by blocking both ERα nuclear and extranuclear signaling and promoting apoptosis in therapy resistant cells. Taken together, our results suggest targeting the ERα-PELP1 axis in combination with current endocrine therapies will enhance therapeutic efficacy and may inhibit or delay development of endocrine therapy resistance. This study is funded by Komen grant KG090447 and NIH grant CA095681. 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 1733. doi:10.1158/1538-7445.AM2011-1733
Studies of in vitro primaquine hemolysis: substrate requirement for erythrocyte membrane damage.
Authors: J N George, R L O'Brien, S Pollack, W H Crosby
Journal: Journal of Clinical Investigation (1966)

The hemolytic toxicity of primaquine has been recognized since its introduction as an antimalarial drug (2, 3). Both in vivo and in vitro primaquine hemolysis has been extensively characterized, but the actual mechanisms of red cell destruction are still unknown (4, 5). These two processes differ from one another in that much greater concentrations of primaquine are required for in vitro hemolysis (6). During this study of the mechanisms of primaquine hemolysis, we made the apparently paradoxical observation that red cells deficient in glucose 6-phosphate dehydrogenase (G-6-PD), although more sensitive than normal cells to primaquine hemolysis in vivo, are less sensitive to primaquine-induced changes in an in vitro system containing substrate. This led us to examine the relationship between erythrocyte metabolism and in vitro primaquine damage.
Pressure-Induced Matrix Metalloproteinase-9 Contributes to Early Hypertensive Remodeling
Authors: Stéphanie Lehoux, Catherine A. Lemarié, Bruno Esposito, H. Roger Lijnen, Alain Tedgui
Journal: Circulation (2004)

High blood pressure causes a change in vascular wall structure involving altered extracellular matrix composition, but how this process occurs is not fully understood.Using mouse carotid arteries maintained in organ culture for 3 days, we detected increased gelatin zymographic activity of matrix metalloproteinase (MMP)-2 (168+/-13%, P<0.05) in vessels kept at low intraluminal pressure (10 mm Hg) compared with vessels at 80 mm Hg (100%), whereas in vessels maintained at high pressure (150 mm Hg), both MMP-2 and MMP-9 activity was induced (182+/-32%, P<0.05, and 194+/-21%, P<0.01, respectively). MMPs were detected in endothelial and smooth muscle cells by immunohistochemistry and in situ gelatin zymography. In vessels at 150 mm Hg, MMP activation was associated with a shift in the pressure-diameter curve toward greater distensibility (P<0.01) compared with vessels at 80 mm Hg. However, distensibility was not altered in vessels at 10 mm Hg, in which only activated MMP-2 was detected. The role of MMPs in high pressure-induced vessel distensibility was confirmed by use of the MMP inhibitor FN-439, which prevented the shift in the pressure-diameter relationship. Furthermore, in carotid arteries from MMP-9-deficient mice, the pressure-dependent increase in MMP-2 and in situ gelatinolytic activity were maintained, but the upward shift in the pressure-diameter curve was abolished.MMP-9 seems to play a key role in the early stages of hypertensive vascular remodeling.
Electrocardiogram and Spatial Vectorcardiogram of Localized Myocardial Hypertrophy
Authors: GEORGE E. BURCH, NICHOLAS P. DEPASQUALE
Journal: Circulation (1962)

Diagnostic electrocardiographic and vectorcardiographic manifestations of localized hypertrophy of the posterobasal portion of the left ventricle and of localized hypertrophy of the crista supraventricularis have been described. Recognition of the fact that only a portion of the myocardium may undergo hypertrophy is important in understanding certain types of electrocardiographic and spatial vectorcardiographic patterns. Several types of localized myocardial hypertrophy for which no characteristic electrocardiographic or spatial vectorcardiographic patterns have been described were also discussed. There is a need for further study of this problem, and, in particular, for detailed correlation of the necropsy data with the electrocardiogram and the vectorcardiogram.
244 ANGIOGENESIS IN PORTAL HYPERTENSIVE NAD(P)HOXIDASE-KNOCKOUT-MICE IS MEDIATED BY A DIFFERENT PATHWAY THAN IN WILDTYPE ANIMALS
Authors: B. Angermayr, T. Reiberger, N. Rohr-Udilova, M. Mitterhauser, D. Cejka, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2008)
PML-RARα and Dnmt3a1 Cooperate <i>in vivo</i> to Promote Acute Promyelocytic Leukemia
Authors: Deepa Subramanyam, Cassandra D. Belair, Keegan Q. Barry-Holson, Haijiang Lin, Scott C. Kogan, Emmanuelle Passegué, Robert Blelloch
Journal: Cancer Research (2010)

The PML-RARα oncogene is the central effector of acute promyelocytic leukemia (APL). PML-RARα physically interacts with epigenetic-modifying enzymes including DNA methyltransferases (Dnmt) to suppress critical downstream targets. Here, we show that increased expression of Dnmt3a1 cooperates with PML-RARα in vivo to promote early lethality secondary to myeloid expansion and dysfunction in primary mice. Bone marrow cells from these mice cause leukemogenesis with a shortened latency and a higher penetrance on transplantation into irradiated recipients. Furthermore, leukemic cells overexpressing PML-RARα and Dnmt3a1 display increased methylation at a target promoter compared with PML-RARα or Dnmt3a1 controls. Our findings show a cooperation between the PML-RARα oncogene and the Dnmt3a1 enzyme in vivo and that Dnmt levels can be rate limiting in APL progression.
Another Source of Lead-Poisoning
Authors: A. Wiltshire
Journal: BMJ (1870)

district, it happened that, after one or two mild seizures' complete re- covery ensued.Much more frequently there was no intermission of perfect health ; the pulse, skin, and tongue might be in their normal state, or nearly so, but the capability of the individual to resist the at- tack was much lqwered; generally, too, during this partial recovery, there continued the sense of prostration, the loss of appetite and of energy, and a dull pain in the neighbourhood of the liver and spleen: remaining, as the majority had to remain, subject to malarious influences, yet properly treated and sufficiently fed, the attacks became more distant, quotidian becoming tertian, quartan, erratic, or ceasing altogether.It is perhaps hardly necessary to say that the stages were not always well marked.We had malaria without fever.Sometimes, but rarely, ty- phoid symptoms occurred; there was no longer an intermission, scarcely a remission ; it became a continued fever with accessions at regular or irregular periods ; in these we had the typhoid symptoms only before death.On examination post mortemi, it was found that Peyer's patches were never involved.The relative frequency of quotidian, tertian, quartan, and erratic was, according to the Civil Hospital returns, as follows :-Quotidian, 82.90; tertian, 13,08; quartan, 0.45; and erratic, 3.57; and my experience would yield somewhat similar results.The sequelre were hzemorrhages, anasarca, ascites, haematuria, constipation, diarrhoea, and, by far the most fatal, dysentery.Theepost e zorten, appearances were very variou; these depended, to some extent, upon whether the patient had yielded to one sudden, sharp attack, or whether he died only after having made a stout resistance.I am greatly indebted to my friend Dr. Dickson of Grande Rivi'ere for in- formation on this subject, and I regret that I am not able to furnish the more exact data that his necropsical journal would afford.There were generally present cerebral congestion and effusion ; after many at- tacks, softening of the brain, which, too, was often stained of a yellow colour.The heart was flaccid ; the ventricles contained yellow fibrin- ous clots, which sometimes extended to a considerable distance into the aorta and pulmonary artery; the liver was enlarged, congested, soft- ened, and friable-more rarely hard and shrivelled ; the spleen much enlarged, and after numerous seizures, of a dark slaty colour, and soft- ened; the mucous membrane of the stomach and intestinal canal was very muclh congested; the kidneys normal, or flabby, white, and bloodless; more rarely shrivelled and dry; more frequently softened.The treatment was that usually adopted:-emetics, purgatives, and antiperiodics during the intermission; stimulants, diaphoretics, and counterirritants during the paroxysm.It was, I think, pretty generally 1870,
The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway
Authors: Rodrigo Liberal, Charlotte R. Grant, Beth S. Holder, Yun Ma, Giorgina Mieli-Vergani, Diego Vergani, Maria Serena Longhi
Journal: Hepatology (2012)

In autoimmune hepatitis (AIH), liver-damaging CD4 T cell responses are associated with defective CD4posCD25pos regulatory T cells (T-regs). Galectin-9 (Gal9), a β-galactosidase–binding protein expressed by T-regs, is key to their function, inhibiting T helper 1 immune responses by binding T cell immunoglobulin and mucin domain 3 (Tim-3) on CD4 effector cells. We investigated whether impaired immunoregulation in AIH results from reduced expression of Gal9 in T-regs and/or Tim-3 on CD4 effector cells. Circulating Gal9posCD4posCD25pos and Tim-3posCD4posCD25neg T cell phenotype was assessed by flow cytometry in 75 AIH patients. To evaluate whether Tim-3 expression renders CD4posCD25neg T cells amenable to T-reg control, purified CD4posCD25negTim-3pos (Tim-3pos) and CD4posCD25negTim-3neg (Tim-3neg) cells were cocultured with T-regs. To determine whether Gal9 expression is essential to function, T-regs were treated with small interfering RNA (siRNA) to repress Gal-9 translation; T-reg suppressor function was assessed by proliferation. In AIH, Tim-3pos cells within CD4posCD25neg cells and their T-betpos and RORCpos subsets were fewer and contained higher numbers of interferon-γ (IFNγ)pos and interleukin (IL)-17pos cells than healthy subjects (HS). In AIH and HS, Tim-3pos cells proliferated less vigorously and were more susceptible to T-reg control than Tim-3neg cells. In AIH, Gal9posT-regs were fewer and contained less FOXP3pos, IL-10pos, and transforming growth factor βpos and more IFNγpos and IL-17pos cells than HS. siRNA treatment of Gal-9pos T-regs drastically reduced T-reg ability to suppress CD4posCD25neg and Tim-3pos cell proliferation in AIH and HS. Tim-3pos cell percentage correlated inversely with aminotransferase and CD25negT-betpos cell values. Conclusion : Reduced levels of Tim-3 on CD4posCD25neg effector cells and of Gal9 in T-regs contribute to impaired immunoregulation in AIH by rendering effector cells less prone to T-reg control and T-regs less capable of suppressing. (HEPATOLOGY 2012)
Interleukin-6 production in posttransplant lymphoproliferative disease.
Authors: G Tosato, K Jones, M K Breinig, H P McWilliams, J L McKnight
Journal: Journal of Clinical Investigation (1993)

IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients with posttransplant lymphoproliferative disease (PTLD), with a mean maximal level of 196.7 U/ml. This represents a 16.4 increase above the normal mean (11.3 U/ml). In contrast, only 3 of 10 solid organ transplant recipients with uncomplicated courses posttransplant had abnormally elevated serum/plasma IL-6 bioactivity (mean maximal level 41.4 U/ml, P = 0.0007). When transferred to single cell culture, the 11 PTLD tissues produced 640 to 1.25 x 10(6) IL-6 U/ml in the culture supernatant, with a mean maximal level of 35,025 IL-6 U/ml. Cell separation experiments demonstrated that the adherent cells, identified as non-B cells, were the principal source of IL-6 production in vitro by PTLD tissue. Control cultures of inflammatory lymphoid tissue negative for lymphoproliferative disease as well as of PBL from patients with acute EBV-induced infectious mononucleosis consistently produced < 10 IL-6 U/ml. Thus, IL-6 is produced at high levels by PTLD tissues and may play a critical role in the pathogenesis of PTLD.
The evolving management of a rare lymphoproliferative disorder–T‐cell prolymphocytic leukemia
Authors: Paolo Gallipoli, Andrew Clark, Mike Leach
Journal: American Journal of Hematology (2009)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. The evolving management of a rare lymphoproliferative disorder: T-cell prolymphocytic leukaemia
Visits Outside Practice Area
Authors: J. P. Lester
Journal: BMJ (1971)

staff and a very different atmosphere from the acute wards.My own experience of geriatric long-stay wards, some with a high proportion of demented patients, is that eventually some trained staff are found who derive much satisfaction from their work.They have to learn to organize them more like homes and not to compete with the acute wards.The geriatrician does not have to spend much time in the long-stay units, but he must set the pattern and have control of admission.This difference of view is a minor matter, however, compared with our general agreement on the development of medical services for elderly people and on the great need for doctors to interest themselves in this field-I am, etc.,
Association of Vitamin D With Insulin Resistance and β-Cell Dysfunction in Subjects at Risk for Type 2 Diabetes
Authors: Giovanna Muscogiuri, Gian Pio Sorice, Annamaria Prioletta, Caterina Policola, Silvia Della Casa, Alfredo Pontecorvi, Andrea Giaccari
Journal: Diabetes Care (2010)

We read with interest the article by Kayaniyil et al. (1) that supplied elegant data suggesting that 25-hydroxyvitamin D [25(OH)D] is related to insulin resistance and β-cell function in a large population at high risk for type 2 diabetes and/or metabolic syndrome, thus concluding that 25(OH)D may be an independent risk factor for diabetes. We have, however, some concerns.

First, the studied population was mainly composed of obese subjects (the mean BMI was 30.5 kg/m2). Clearly, within a …
Vitamin C in Orange Juice
Authors: William R. Barclay
Journal: JAMA (1977)

<h3>Editor's Note—</h3> <i>Values given for vitamin C in a previous</i>Journal<i>article</i>(235:2624, 1976)<i>may have been incorrectly high. An article in</i>Consumer Reports (November 1976, p 612)<i>charges that an inaccurate analytical method was used</i>.
Platelet activating factor: a potent constrictor of cerebral arterioles in newborn pigs.
Authors: W M Armstead, M Pourcyrous, R Mirro, C W Leffler, D W Busija
Journal: Circulation Research (1988)

This study characterized the nature of the response to platelet activating factor (PAF) in the cerebral microcirculation of the newborn pig. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of 10-100 ng/ml PAF produced dose-dependent decreases in pial arteriolar diameter; diameters were 193 +/- 27 microns for control, 167 +/- 25 microns at 10 ng/ml, and 129 +/- 21 microns at 100 ng/ml. Topical application of 30-300 ng/ml norepinephrine and 3-30 ng/ml U46619, a purported thromboxane A2 receptor agonist, also produced dose-dependent decreases in pial arteriolar diameter. After topical administration of U66985 (1 microgram/ml), a putative PAF antagonist, responses to PAF were attenuated significantly, but responses to norepinephrine and U46619 were unchanged. Moreover, intravenously administered U66985 (0.1 mg/kg) antagonized PAF responses as well. Responses to PAF were unchanged after cyclooxygenase and leukotriene receptor inhibition. Further, PAF did not increase cortical subarachnoid cerebrospinal fluid prostaglandin or leukotriene levels. These data indicate that PAF is a potent constrictor of cerebral arterioles in newborn pigs and that its mechanism of action is independent of formation of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These data also suggest that U66985 may be a selective PAF antagonist that crosses the blood-brain barrier. Since PAF is an endogenous lipid released from a variety of tissues and may be an important mediator of inflammation and allergic reaction, PAF could be involved in the pathophysiology of the cerebral circulation in the perinatal period.
The Persistent Suicidal Patient
Authors: CHARLES WATKINS, J. E. GILBERT, WILLIAM BASS
Journal: American Journal of Psychiatry (1969)

Stimulated by their observation of a patient who persistently attempted suicide, the authors conducted a survey to determine the incidence of similar behavior among other hospitalized psychiatric patients. Reports from 53 hospitals indicated that highly unusual methods are devised by patients who are under greater supervision because of previous attempts. The authors conclude that these patients will require even more serious staff effort as trends in care tend to liberalize.