tbuckley/cabot-search huggingface dataset:
Vasodilator Therapy for Primary Pulmonary Hypertension
Authors: MILTON PACKER
Journal: Annals of Internal Medicine (1985)

Vasodilator drugs were initially administered to patients with primary pulmonary hypertension based on the unproven hypothesis that pulmonary vasoconstriction played an important role in the pathogenesis of the disease. There were early reports of hemodynamic and clinical improvement after treatment with various vasodilating agents, but subsequent experience did not confirm these uncontrolled observations, and emphasized the limitations and hazards of this approach. Vasodilator therapy generally fails to reduce pulmonary vascular resistance selectively during long-term administration and frequently leads to systemic hypotension, exacerbation of the pulmonary hypertensive state, worsening of right ventricular failure, and systemic arterial desaturation. Beneficial hemodynamic responses are seen in only 15% to 25% of patients. Vasodilator therapy should not be considered an established treatment of patients with primary pulmonary hypertension.
Cases of Idiopathic Pneumothorax, with Remarkable Absence of Bad Symptoms: Recovery
Authors: J. Thorburn
Journal: BMJ (1860)

agent; but it was also productive of evil, as it gave rise to the abuse of the system in a manner precisely analogous to that in which various systems of charlatanism lave been carried out in modern times.12. The state of medical matters at which we are now arrived shows four influences at work, directly or indirectly, on the science of medicine.These are, (a) the empirical Lknowledge of the ZEsculapian priests, and their study of disease per se in regard to its diagnosis, as at Cnidos, and in regard to its semeiology and prognosis, as at Cos; (b) the introduction of hypothesis by the philosophers; (c) the introduction of anatorny and physiology; (d) the application, more closely and extensively than hitherto, of a system of hygiene, consisting principally in dietetics and gymnastics. CASES OF IDIOPATHIC PNEUMOTHORAX, WITH REMARKABLE ABSENCE OF BADSYMPTOMS: RECOVERY.
Mitochondrial Ca2+ uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion☆
Authors: M RUIZMEANA, D GARCIADORADO, E MIROCASAS, A ABELLAN, J SOLERSOLER
Journal: Cardiovascular Research (2006)

Reenergization of ischemic cardiomyocytes may be associated with acute necrotic cell death due in part to cytosolic Ca2+ overload and opening of a permeability transition pore (PTP) in mitochondria. It has been suggested that Ca2+ overload during ischemia primes mitochondria for PTP opening during reperfusion. We investigated the ability of mitochondria to uptake Ca2+ during simulated ischemia (SI) and whether this uptake determines PTP opening and cell death upon simulated reperfusion (SR).Rat heart mitochondria were submitted to either hypoxia (anoxic chamber) or to SI (respiratory inhibition, substrate depletion and acidosis) and subsequent SR. Mitochondrial Ca2+ uptake was monitored using Ca2+ microelectrodes after exposure to different [Ca2+] up to 25 microM during SI, and PTP opening was assessed by quantification of mitochondrial swelling (changes in absorbance rate at 540 nm) and calcein release. Mitochondrial Ca2+ uptake (Rhod-2 fluorescence) and cytosolic Ca2+ rise (Fura-2 ratio fluorescence) were further investigated in HL-1 cardiac myocytes submitted to SI/SR, and the effect of reducing mitochondrial Ca2+ load (with 25 microM ruthenium red) or blocking PTP opening (with 0.5 microM cyclosporin A) on the rate of cell death was investigated in adult cardiomyocytes exposed to SI/SR.SI induced a progressive dissipation of mitochondrial membrane potential (TMRE fluorescence); however, prior to the completion of depolarization, high levels of Ca2+ uptake were observed in mitochondria. SR induced PTP opening but this phenomenon was not influenced by the magnitude of mitochondrial Ca2+ uptake during previous SI. Blockade of the mitochondrial Ca2+ uniporter during SI in cardiomyocytes attenuated mitochondrial Ca2+ uptake but increased cytosolic Ca2+ overload and cell death upon subsequent SR.Mitochondrial Ca2+ uptake during SI buffers cytosolic Ca2+ overload but its magnitude appears not to be an important determinant of PTP opening upon subsequent SR.
Multicenter, double-blind, placebo-controlled trial of terfenadine suspension in the treatment of fall-allergic rhinitis in children
Authors: M GUILL, R BUCKLEY, W ROCHAJR, J KEMP, A SEGA, L SHIRLEY, D TINKELMAN, Z SHAATHSCHWEN, K DIETRICH, L WILLE
Journal: Journal of Allergy and Clinical Immunology (1986)
Estrogen Receptor-Mediated Repression of Target Genes: Mechanism of Action, and Biological Significance.
Authors: S. Oesterreich, S. Jiang, E. Verdin, A. Lee, S. Malik
Journal: Cancer Research (2009)

Abstract Estrogen-bound estrogen receptor (ER) can regulate the transcription of a large number of genes. Although estrogen represses as many genes as it induces, induction has been studied in detail while the repression mechanisms remain largely unknown. In this study we characterized several estrogen-repressed ERα target genes that are directly repressed by estrogen in breast cancer cells. Interestingly, many repressed genes are tumor suppressor genes, playing critical roles in cell cycle inhibition and/or apoptosis. One gene that particularly piqued our interest is Reprimo (RPRM) because of its robust repression in a number of cell lines, and its role as a cell cycle inhibitor. Additionally, it is highly methylated in a variety of cancers including breast cancer and maps to a locus that displays loss of heterozygosity, suggesting that it may be a tumor suppressor gene. As a result, E2-mediated repression of this gene may be a crucial step in the progression of breast cancer. We did show that RPRM decrease (by siRNA) enhances estrogen-mediated S-phase entry, strongly suggesting a biological role of its repression. RPRM was actively and strongly repressed by estrogen and this repression was not due to a quicker turnover of the RPRM mRNA by estrogen. E2-mediated repression of RPRM levels did not require new protein synthesis since it is also repressed in the presence of the translation inhibitor, cycloheximide. We find that estrogen repression of RPRM requires a tripartite interplay between ERα, FoxA1, and HDAC7 as knockdown of these proteins abrogates its repression. Remarkably, silencing of HDAC7 significantly relieved repression of the majority of eleven estrogen-repressed genes tested. Further examination of the interplay between HDAC7 and ERα revealed that HDAC7 can interact with ERα and repress its transcriptional activity in a deacetylase-independent manner. Chromatin immunoprecipitation assays demonstrate that ERα, FoxA1, and HDAC7 are all recruited to a cis-regulatory enhancer (-4.8 kb) in the RPRM gene in the presence of estrogen, which was associated with a release of RNA Pol II from the proximal promoter. Repression requires FoxA1 to be recruited to an epigenetic signature characterized by H3K4 mono- and di-methylation. In summary, we have uncovered a unique requirement for a deacetylase-independent function of HDAC7 in estrogen repression of genes such as RPRM. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4136.
Major Drug Interactions: Effect of Liver Disease, Alcohol, and Malnutrition
Authors: A M Hoyumpa, S Schenker
Journal: Annual Review of Medicine (1982)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Please do not resuscitate: Communication is key
Authors: Gordon Lishman
Journal: BMJ (2006)

Solution is flawedEditor-Conroy et al offer a challenging solution to advance decisions on cardiopulmonary resuscitation (CPR), but the basis for that solution is fundamentally flawed. 1 They start from the premise that all institutions should provide cardiopulmonary resuscitation unless an overt decision has been made to the contrary. 2 3This is a common position in most UK NHS trusts, but there is no ethical, legal, or clinical demand on professionals that they must provide CPR.Current UK guidelines describe a presumption in favour of CPR in the absence of an advance decision but are equally clear that it would be unreasonable to resuscitate anyone in whom the burdens of treatment clearly outweigh the potential benefits.The presumption in favour of CPR has been interpreted by many health authorities as a default for CPR, but such a position is not supported by the guidelines and runs counter to personalised decision making by removing personal choice.It is also exceptional, since no other medical treatment comes with a default position.Unfortunately, Conroy et al's solution is to suggest an equally unacceptable position, a default against CPR.Conroy et al are right that the current guidelines need to be reviewed, but not for the reasons they state.Current UK guidelines are the source of much confusion among clinicians. 4They contain many contradictions and confusing statements and provide no framework for making clinical decisions.It is possible to make sense of advance decisions on CPR, and had the authors done so they would have arrived at a framework that individualises decisions, involves patients or relatives and partners when appropriate, and does so without placing an unnecessary burden on patients and carers. 4Instead the authors try to work through this confusion, and by offering a default against CPR they fail to reach a caring solution.
An Approach to the Performance of Contrast Studies in Contrast Material-Reactive Persons
Authors: BURTON ZWEIMAN
Journal: Annals of Internal Medicine (1975)

A method of carrying out contrast studies was considered for use in 124 persons with past histories of adverse reactions to contrast media. High-dosage steroid treatment was given before and during the contrast study to 37 patients with previous rash responses and 9 with prior anaphylactoid reactions; only 3 and 1 patients, respectively, of these groups had mild adverse reactions. Patients with past reactions deemed "vasomotor" underwent contrast study without preparative drug therapy without significant adverse effects. Although uncontrolled, this study suggests a possible protective role of steroids In patients with certain previous reactions to contrast media. We do not wish to Imply that this is the only approach that can be used in the kind of patients reported here.
Hospital Volume and Surgical Mortality in the United States
Authors: John D. Birkmeyer, Andrea E. Siewers, Emily V.A. Finlayson, Therese A. Stukel, F. Lee Lucas, Ida Batista, H. Gilbert Welch, David E. Wennberg
Journal: New England Journal of Medicine (2002)

Although numerous studies suggest that there is an inverse relation between hospital volume of surgical procedures and surgical mortality, the relative importance of hospital volume in various surgical procedures is disputed.
Scientific Basis of Drug Dependence
Authors: Donald W. Goodwin
Journal: JAMA (1970)

When asked to give a talk about drugs these days, a speaker may safely assume that the audience will not expect a lecture on, say, digitalis or insulin. Each age confers upon the term "drugs" it own meaning. Today the word refers mainly to opiates, barbiturates, amphetamines, marihuana and other hallucinogens. But 60 years ago, as Aubrey Lewis observes in his contribution to this book, drugs meant—in addition to morphia and alcohol—chloroform, ether, chloral, sulphonal, phenacetin, tobacco, tea, and coffee. All were used recreationally and identified in some vague way with sin, and all could produce dependence or addiction, terms as monumentally fuzzy then as today. Among the papers in this symposium, Lewis' is particularly rewarding because it provides historical perspective where historical perspective is in short supply. Consider, for example, turn-of-the-century attitudes towards coffee, tea, and tobacco. The latter, according to one eminent Victorian pharmacologist quoted by Lewis, produced
Abstract 3580: Discovery and SAR study of a novel and potent Itk inhibitor as a targeted therapeutic agent for T-cell lymphoma and leukemia
Authors: Ruiwu Liu, Wenchang Guo, Aihong Ma, Eduardo Sanchez, Yan Wang, Jixian Li, Chunping Xu, Jinying Ning, Wenzhe Huang, Anisha Mazloom, Aimin Song, Kit S. Lam, Michelle Xia, Yiyou Chen, Hsing-Jien Kung
Journal: Cancer Research (2011)

Abstract Itk (IL2-inducible T-cell kinase) is a non-receptor protein tyrosine kinase. It is selectively expressed in T cells, Mast cells, and NK cells. It plays an important role in T-cell maturation, proliferation, and malignancies. Using Western blotting, Itk was only detected in three T-cell lymphoma and leukemia cell lines (Jurkat, Molt-4, and Hut78) out of 41 different cancer cell lines. A small molecule named CTA056 showed potent and selective inhibition of Itk kinase activity and growth in each of the three T-cell cancer cell lines. After treatment of Jurkat cells with CTA056, Itk phosphorylation was inhibited in a dose-dependent manner. In addition, apoptosis was induced in Jurkat cells following treatment with CTA056. In order to better understand structure-activity relationship (SAR) on CTA056, a series of analogs of CTA056 were designed, synthesized, and tested for their inhibition of both Itk phosphorylation and cancer cell growth. Several analogs showed better activity and selectivity. The results will be presented. Success in this endeavor could lead to the development of novel targeted therapy, rather than traditional chemotherapy, for T-cell lymphomas and leukemia. 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 3580. doi:10.1158/1538-7445.AM2011-3580
CANCER OF THE SKIN.
Authors: Henry Maccormac
Journal: British Journal of Dermatology (1940)

Journal Article CANCER OF THE SKIN. Get access Henry Maccormac, C.B.E, M.D., F.R.C.P. Henry Maccormac, C.B.E, M.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 52, Issue 5, 1 May 1940, Pages 141–155, https://doi.org/10.1111/j.1365-2133.1940.tb10859.x Published: 01 May 1940
Randomised controlled trial of transjugular intra-hepatic portosystemic stent-shunt (TIPSS) versus tipss and variceal band ligation (VBL) in the prevention of variceal rebleeding
Authors: D. Tripathi, A. Helmy, H.F. Lui, A.J. Stanley, E. Forrest, D.N. Redhead, R. Jalan, P.C. Hayes
Journal: Journal of Hepatology (2001)
Urinary Indoles in Mental Patients
Authors: Herbert Sprince
Journal: JAMA (1963)

To the Editor:—  In a recent issue ofThe Journal( 184 :280 [April 27] 1963), a paper by A. R. Krall and associates entitled Studies on Urinary Indoles in Mental Patients refers to work from this laboratory. In this regard, I feel several comments may be in order.   The conclusions of the authors in the above paper compared with those of their prior abstract (JAMA 180:766 [June 2] 1962) appear to be contradictory. Their abstract reads as follows: Over 200 patients' and about 100 normal subjects' urines have been tested to date, some as many as 20 times. Very few of the normals have shown a high total urinary indole content, while most of the patients do.  The extraction procedure used by Krall and his colleagues suffers from a serious defect. It does not utilize a salting out procedure to insure completeness of extraction. They unwittingly reverted to an
Abstract 4504: Genetic determinants of AKT-dependence in epithelial ovarian cancer
Authors: Aphrothiti J. Hanrahan, Stefano Scarperi, Rita A. Sakr, Maggie L. Westfal, Jason Godsell, Manickam Janakiraman, Douglas A. Levine, Qing-Bai She, Neal Rosen, David B. Solit
Journal: Cancer Research (2010)

Abstract Ovarian cancer is a genetically complex disease. Recent data compiled by The Cancer Genome Atlas Project highlights the heterogeneity within this disease, though distinct genetic signatures, such as PI3K pathway aberration, KRas alteration and Rb loss, are emerging that may condition treatment response. The high frequency of AKT activation in ovarian cancer, via PTEN mutation/deletion, PIK3CA/AKT mutation/amplification, RAS mutation, or mutation/amplification of upstream receptor tyrosine kinases (RTK), suggests that inhibitors of this pathway may be particularly effective treatments for this disease. We utilized a selective, allosteric inhibitor of AKT to determine the AKT-dependence of a panel of ovarian cancer cell lines. This AKT1/2 inhibitor (Merck AKTi-1/2) has been extensively tested against panels of kinases and PH-domain containing proteins and based upon these studies appears to be highly selective for AKT1 and AKT2. The drug effectively inhibited AKT activity as measured by a decrease in AKT phosphorylation at serine 473 in all cell lines. Of the 17 cell lines tested to date, 3 were hypersensitive (IC50 = 0.1um) to AKT inhibition, while 1 demonstrated intermediate sensitivity (IC50 = 2uM) and 13 were resistant (IC50 &amp;gt;=5uM). Levels of AKT phosphorylation at serine 473 were inversely correlated with Merck AKTi-1/2 IC50 (p = 0.036) but AKT activation alone was insufficient to confer sensitivity. Activation of the MAPK pathway, via KRas/BRaf/MEK1 mutation or KRas amplification, and Rb loss were predictive of resistance to AKT inhibition. In sensitive cell lines, AKT inhibition resulted in hypophosphorylation of RB and accumulation of cells in G1. Significant induction of apoptosis was not observed even in PTEN null, AKT2 amplified and PIK3CA mutant models. Treatment of a PTEN-mutant xenograft model of ovarian cancer with the AKTi-1/2 was also effective in inhibiting AKT phosphorylation and downstream signaling and resulted in a cytostatic tumor response. Ongoing studies are focused on the identification of rational combination strategies that result in induction of apoptosis in the cell lines in which the AKTi-1/2 alone induces growth arrest. The long-term goal will be to identify genetic predictors of AKT-dependence and AKT-inhibitor resistance to guide patient selection for future clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4504.
Outcome in children with purpura fulminans: Report on 16 patients
Authors: Aytemiz Gürgey, Selin Aytac, Guler Kanra, Gulten Secmeer, Mehmet Ceyhan, Cigdem Altay
Journal: American Journal of Hematology (2005)

Abstract Purpura fulminans (PF) is a severe disorder of acute onset with high morbidity and mortality. In children, this rapidly progressive illness is usually associated with severe bacterial or viral infections. However, some other conditions may participate in the development of PF. Our objective was to investigate the underlying and associated disorders and the outcomes of the disease in 16 children, 7 males and 9 females ranging in age from 3.5 months to 12 years (median age, 2 years). Thirteen of the 16 children (81%) were 4 years of age or younger. The remaining 3 patients were 9, 10, and 12 years of age. Among these 13 infants and small children, 7 (43%) had infection, 2 infants had congenital cardiac disorders necessitating minor or major surgical intervention, and 1 infant and 3 children had different miscellaneous disorders. The factor V G1691A mutation was present in six of the 13 small children (46%). None of the 3 older children carried the mutation. Six (37.5%) of the 16 patients had protein C deficiencies, and 9 (56%) had protein S deficiencies. These deficiencies, except one for protein S, were acquired. Ten patients except two who were diagnosed at this center were treated with fresh frozen plasma. They were also given heparin. Nine (69%) of the 13 children 4 years of age or younger and one of the older children (33%) required amputation. Five of the six patients (83%) who had factor V G1691A mutation, and who also exhibited severe infection, required amputation. This study suggests that an age of 4 years or less is a risk factor for the development of PF during severe infections, especially in the presence of factor V G1691A mutation and congenital heart disease, necessitating major or minor surgical interventions. This study also shows that the amputation rate in 10 patients, after excluding the patients who had been referred to our center after development of sequelae, was 60%. The survival rate among these 10 patients may indicate that, with the treatment protocol, PF need not be regarded as a lethal disease any more. It is also suggested that effective immunization programs and better health care have probably resulted in some changes in the etiological profile of PF. Am. J. Hematol. 80:20–25, 2005. © 2005 Wiley‐Liss, Inc.
A Comparison of the Requirements for Primary Care Physicians in HMOs with Projections Made by the GMENAC
Authors: Donald M. Steinwachs, Jonathan P. Weiner, Sam Shapiro, Paul Batalden, Kathy Coltin, Fred Wasserman
Journal: New England Journal of Medicine (1986)

Abstract We compared staffing patterns in primary care specialties in three large health maintenance organizations (HMOs) with the national requirements for physicians in 1990 projected by the Graduate Medical Education National Advisory Committee (GMENAC). The HMOs varied in their use of nonphysician providers, family practice specialists, and subspecialists in internal medicine. Nevertheless, projections based on the average experience of these HMOs suggest that 20 percent fewer primary care physicians for children and 50 percent fewer primary care physicians for adults will be needed to meet national primary care needs in 1990 than projected by the GMENAC. As enrollment in HMOs continues to grow, their impact on national requirements for medical personnel will increase. The variety of staffing patterns found among HMOs operating in highly competitive markets suggests the importance of considering alternative configurations for meeting national requirements for primary care. (N Engl J Med 1986; 314:217–22.)
Fibroblasts modulate intestinal secretory responses to inflammatory mediators.
Authors: H M Berschneider, D W Powell
Journal: Journal of Clinical Investigation (1992)

Cultured colonic epithelial cells and fibroblasts were used to examine the interaction between these cell types during intestinal secretion. Secretory responses of T84 colonic epithelial cells, measured as changes in the short-circuit current in modified Ussing chambers to bradykinin, serotonin, hydrogen peroxide, and histamine, were enhanced in the presence of fibroblasts, either in cocultures or when separate cultures of fibroblasts were acutely juxtaposed with the T84 cultures. This effect was abolished by pretreatment with indomethacin and the fibroblasts were found to release prostaglandin E2 in response to these inflammatory mediators. Fibroblasts may exert a paracrine regulation on the secretory response of intestinal epithelial cells via the generation and release of cyclooxygenase products in response to inflammatory mediators. These studies suggest a novel function for the intestinal fibroblastic sheath: that of amplification of the inflammatory response through mesenchymal/epithelial interaction.