tbuckley/cabot-search huggingface dataset:
Sympathectomy for Essential Hypertension
Authors: EDGAR V. ALLEN
Journal: Circulation (1952)

The successful treatment of essential hypertension remains one of the most difficult problems in medicine. Approximately 18 years have elapsed since extensive sympathectomy was first performed for essential hypertension. Extensive sympathectomy occasionally produces striking decrease in blood pressure of patients with essential hypertension; in many instances it fails to decrease blood pressure or modify the course of the disease. That which is most desired are some standards for preoperative selection of patients so that only patients who will be benefited by sympathectomy will be operated on. Unfortunately this apparently cannot be accomplished. The indications for sympathectomy remain at least partially uncertain and there is no agreement among those most experienced in the field of hypertension relative to the results of operation. There also are differences of opinion about the extensiveness of sympathectomy which is advisable. This paper indicates clearly differences of opinion among those most experienced in this field and emphasizes some of the points of agreement. It seems clear that additional technics of sympathectomy cannot be devised for the treatment of essential hypertension. There seems little doubt that sympathectomy would not be performed were adequate medical treatment available. This presentation gives the opinion of internists and surgeons who are particularly interested in hypertension and its treatment.
Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia.
Authors: A M Farese, P Hunt, L B Grab, T J MacVittie
Journal: Journal of Clinical Investigation (1996)

This study compared the therapeutic potential of recombinant, native versus pegylated megakaryocyte growth and development factor (rMGDF and PEG-rMGDF, respectively), as well as that of the combined administration of PEG-rMGDF and r-methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) on hematopoietic reconstitution after 700 cGy, 60Co gamma, total body irradiation in nonhuman primates. After total body irradiation, animals received either rMGDF, PEG-rMGDF, r-metHuG-CSF, PEG-rMGDF and r-metHuG-CSF or HSA. Cytokines in all MGDF protocols were administered for 21-23 d. Either rMGDF, PEG-rMGDF, or PEG-rMGDF and r-metHuG-CSF administration significantly diminished the thrombocytopenic duration (platelet count (PLT) < 20,000 per microliter)to o.25, 0, 0.5 d, respectively, and the severity of the PLT nadir (28,000, 43,000, and 30,000 per microliter, respectively) as compared with the controls (12.2 d duration, nadir 4,000 per microliter), and elicited an earlier PLT recovery. Neutrophil regeneration was augmented in all cytokine protocols and combined PEG-rMGDF and r-metHuG-CSF further decreased the duration of neutropenia compared with r-metHuG-CSF alone. These data demonstrated that the administration of PEG-rMGDF significantly induced bone marrow regeneration versus rMGDF, and when combined with r-metHuG-CSF significantly enhanced multilineage hematopoietic recovery with no evidence of lineage competition.
Personal Awareness and Effective Patient Care
Authors: Roy Poses, Robert S. Wigton, Randall D. Cebul
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Dr Novack and colleagues<sup>1</sup>made assertions about physicians' decision making and how it can be improved that seemed to go beyond the available evidence. First, their statements about what influences physicians' decision making seemed to be based on studies of association that may have been confounded. For example, to support their statement "physicians'effectiveness... depends on a variety of personal factors," they cited the studies by Nightingale and Grant that showed associations between physicians' responses to a written instrument designed to assess their response to risks and their patterns of utilization, eg, the length of time they conduct cardiopulmonary resuscitation.<sup>2</sup>However, the work of Nightingale and Grant could not determine whether risk attitudes directly affected decision making or were simply a marker for something else that did. Likewise, to support the statement "sex thus affects... clinical decisions," Novack and colleagues cited a study in which the authors concluded, "it
Exposure of platelet fibrinogen receptors by ADP and epinephrine.
Authors: J S Bennett, G Vilaire
Journal: Journal of Clinical Investigation (1979)

The role of fibrinogen as a cofactor for platelet aggregation was examined by measuring the binding of 125I-labeled human fibrinogen to gel-filtered human platelets both before and after platelet stimulation by ADP and epinephrine. Platelet stimulation by ADP resulted in the rapid, reversible binding of fibrinogen to receptors on the platelet surface. Fibrinogen binding increased as the concentration of ADP was increased from 0.1 to 2 microM, reaching a plateau at higher ADP concentrations. Binding occurred only after platelet stimulation and in the presence of divalent cations. However, fibrinogen binding did not occur to ADP-stimulated platelets from three patients with Glanzmann's thrombasthenia. Analysis of fibrinogen binding as a function of increasing fibrinogen concentration demonstrated that maximal platelet stimulation exposed approximately or equal to 45,000 binding sites per platelet with a dissociation constant of 80--170 nM. These fibrinogen binding parameters were essentially the same whether ADP or epinephrine was the platelet-stimulating agent. Thus, these studies demonstrate that platelet stimulation by ADP and epinephrine exposes a limited number of fibrinogen receptors on the platelet surface. Furthermore, these data suggest that the fibrinogen molecules bound to the platelet as a consequence of platelet stimulation are directly involved in the platelet aggregation response.
Influence of Modified Corticosteroids on Antitryptic Activity of Rat Serum
Authors: WILLIAM F. BLATT, EDWARD H. SCHAEFER, JOHN ZYLBER, H. JENSEN
Journal: Circulation Research (1958)

This report deals with the influence of cortisone, prednisolone, prednisone and 9 α-fluorocortisol acetate on the serum antitryptic activity of normal, splenectomized, adrenalectomized and adrenalectomized-splenectomized rats. Elevation of serum antitryptic activity was most consistent with 9α-fluorocortisol acetate administration. Prednisolone and prednisone proved less effective while cortisone-induced changes were of small magnitude.
Severe Hypocalcemia after Intravenous Bisphosphonate Therapy in Occult Vitamin D Deficiency
Authors: Clifford J. Rosen, Sue Brown
Journal: New England Journal of Medicine (2003)

To the Editor: Oral bisphosphonates are effective for the prevention and treatment of osteoporosis. Powerful second- and third-generation parenteral bisphosphonates, including pamidronate and zoled...
Number of land mine victims in Kosovo is high
Authors: E G Krug, A Gjini A
Journal: BMJ (1999)

EDITOR—On 9 June 1999, the governments of the Federal Republic of Yugoslavia and of the Republic of Serbia signed a military technical agreement with the NATO-led international security force (KFOR) concerning the situation in Kosovo. During the following four weeks more than 650 000 Kosovar refugees returned home. The number of people with fatal and non-fatal injuries caused by antipersonnel mines needs to be determined to plan mine awareness and demining campaigns accordingly.

On 7-14 July 1999, the World Health Organisation conducted an assessment to determine …
Development of an antibody that neutralizes soluble IgE and eliminates IgE expressing B cells
Authors: Andrew C Nyborg, Anna Zacco, Rachel Ettinger, M Jack Borrok, Jie Zhu, Tom Martin, Rob Woods, Christine Kiefer, Michael A Bowen, E. Suzanne Cohen, Ronald Herbst, Herren Wu, Steven Coats
Journal: Cellular and Molecular Immunology (2015)

Immunoglobulin E (IgE) plays a key role in allergic asthma and is a clinically validated target for monoclonal antibodies. Therapeutic anti-IgE antibodies block the interaction between IgE and the Fc epsilon (Fcε) receptor, which eliminates or minimizes the allergic phenotype but does not typically curtail the ongoing production of IgE by B cells. We generated high-affinity anti-IgE antibodies (MEDI4212) that have the potential to both neutralize soluble IgE and eliminate IgE-expressing B-cells through antibody-dependent cell-mediated cytotoxicity. MEDI4212 variants were generated that contain mutations in the Fc region of the antibody or alterations in fucosylation in order to enhance the antibody's affinity for FcγRIIIa. All MEDI4212 variants bound to human IgE with affinities comparable to the wild-type (WT) antibody. Each variant was shown to inhibit the interaction between IgE and FcεRI, which translated into potent inhibition of FcγRI-mediated function responses. Importantly, all variants bound similarly to IgE at the surface of membrane IgE expressing cells. However, MEDI4212 variants demonstrated enhanced affinity for FcγRIIIa including the polymorphic variants at position 158. The improvement in FcγRIIIa binding led to increased effector function in cell based assays using both engineered cell lines and class switched human IgE B cells. Through its superior suppression of IgE, we anticipate that effector function enhanced MEDI4212 may be able to neutralize high levels of soluble IgE and provide increased long-term benefit by eliminating the IgE expressing B cells before they differentiate and become IgE secreting plasma cells.
The Pleiotropic Effects of Natural AAV Infections on Liver-directed Gene Transfer in Macaques
Authors: Lili Wang, Roberto Calcedo, Huan Wang, Peter Bell, Rebecca Grant, Luk H Vandenberghe, Julio Sanmiguel, Hiroki Morizono, Mark L Batshaw, James M Wilson
Journal: Molecular Therapy (2009)

Adeno-associated viral (AAV) vectors hold great potential for liver-directed gene therapy. Stable and high levels of transgene expression have been achieved in many murine models. Systemic delivery of AAV vectors in nonhuman primates (NHPs) that are natural hosts of AAVs appear to be challenging due to the high prevalence of pre-existing neutralizing antibodies (NAbs). This study evaluates the performance of AAV8, hu.37, and rh.8 vectors expressing green fluorescent protein (GFP) from a liver-specific promoter in rhesus macaques. Two of the animals that received AAV8 showed transduction of 24 and 40% of hepatocytes 7 days after systemic vector delivery. Importantly, expression was detected in several animals after 35 days despite the elevation of liver enzymes and development of transgene-specific T cells in liver. Pre-existing low levels of NAbs profoundly impacted the outcome of gene transfer and redirected vector DNA to spleen. We developed a sensitive in vivo passive transfer assay to detect low levels of NAbs to these novel AAV serotypes. Other strategies need to be developed to reduce immune response to the transgene in order to maintain long-term gene expression. Adeno-associated viral (AAV) vectors hold great potential for liver-directed gene therapy. Stable and high levels of transgene expression have been achieved in many murine models. Systemic delivery of AAV vectors in nonhuman primates (NHPs) that are natural hosts of AAVs appear to be challenging due to the high prevalence of pre-existing neutralizing antibodies (NAbs). This study evaluates the performance of AAV8, hu.37, and rh.8 vectors expressing green fluorescent protein (GFP) from a liver-specific promoter in rhesus macaques. Two of the animals that received AAV8 showed transduction of 24 and 40% of hepatocytes 7 days after systemic vector delivery. Importantly, expression was detected in several animals after 35 days despite the elevation of liver enzymes and development of transgene-specific T cells in liver. Pre-existing low levels of NAbs profoundly impacted the outcome of gene transfer and redirected vector DNA to spleen. We developed a sensitive in vivo passive transfer assay to detect low levels of NAbs to these novel AAV serotypes. Other strategies need to be developed to reduce immune response to the transgene in order to maintain long-term gene expression.
Abstract LB-124: Histone deacetylase 5 stabilizes HIF-1α through Hsp70 deacetylation in cytosol
Authors: Shuyang Chen, Chengqian Yin, Taotao Lao, Dongming Liang, Nianli Sang
Journal: Cancer Research (2014)

Abstract Hypoxia is frequently associated with solid tumors and ischemic disorders, which are the top two leading causes of mortality in the world. Hypoxia-inducible factor 1 is a major regulator of angiogenesis and cellular adaptation to hypoxia. Accordingly HIF-1 function has been considered a therapeutic target for multiple diseases. Histone deacetylase (HDAC) activity has been involved in regulating HIF function and some HDAC inhibitors (HDACIs) have been documented to repress HIF-1 function. However, histone deacetylases encompass multiple members, each has different cellular functions. HDACIs in clinical application or under development generally inhibit more than one HDAC. It is unclear which specific member of the HDAC family is required for HIF-1 function. We present data here to show that histone deacetylase 5 (HDAC5) is required for HIF-1α protein stability. Knockdown of HDAC5 impaired hypoxic accumulation of HIF-1α and HIF-1 function. Furthermore, overexpression of HDAC5 enhanced HIF-1α stability and nuclear accumulation. Specifically, HDAC5 mutant exclusively localized at cytosol is sufficient for this function, stabilizing HIF-1α more efficiently than wild-type HDAC5. We further demonstrate that heat shock 70 kD protein (Hsp70) is a cytosolic substrate of HDAC5; and acetylation of Hsp70 promotes its association with HIF-1α and HIF-1α degradation. Taken together, our data suggest that deacetylation of Hsp70 catalyzed by HDAC5 facilitates the stabilization and hypoxic accumulation of HIF-1α. These findings also suggest that HDAC5 could be a potential target for therapies based on modulating HIF-1 function. Citation Format: Shuyang Chen, Chengqian Yin, Taotao Lao, Dongming Liang, Nianli Sang. Histone deacetylase 5 stabilizes HIF-1α through Hsp70 deacetylation in cytosol. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-124. doi:10.1158/1538-7445.AM2014-LB-124
Abstract LB-278: MicroRNA control of GNA13 expression and cancer cell invasion
Authors: Suhail Ahmed Kabeer Rasheed, Cui Rong Teo, Emmanuel Beillard, P. Mathijs Voorhoeve, Patrick Casey
Journal: Cancer Research (2012)

Abstract Heterotrimeric guanine nucleotide binding proteins (G proteins) transmit a variety of extracellular signals from cell surface G protein-coupled receptors (GPCRs) to intracellular effector molecules. Heterotrimeric G proteins are classified according to the α subunit into four subfamilies: Gs, Gi, Gq, and G12. The G12 subfamily, which is comprised of two members, Gα12 (GNA12) and Gα13 (GNA13), has been implicated in cancer cell invasion and metastasis. G12 signaling promotes prostate, breast and ovarian cancer cell invasion in vitro, and these proteins are highly expressed in metastatic cancer tissues. As part of a program to elucidate the mechanisms by which GNA12 and GNA13 expression is upregulated in cancer cells, we assessed the potential involvement of micro-RNAs (miRNAs) in post-transcriptional control of GNA13 expression. The initial focus was on prostate cancer; LnCAP (with the lowest GNA13 protein level) and PC3 (with the highest GNA13 level) were employed as the model system. Expression analysis of miRNAs predicted to bind the 3′UTR of GNA13 revealed that miR-182 and miR-141/200a showed an inverse correlation to the protein expression in LnCAP and PC3 cells. Ectopic expression of miR-182 and miR-141/200a in PC3 cells significantly reduced mRNA and protein levels, as well as GNA13 3′UTR- reporter activity. Further, expression of these miRNAs significantly inhibited PC3 cell invasion in an in vitro matrigel invasion assay, and this effect was blocked by overexpression of GNA13 in these cells. Importantly, inhibition of miR-182 and miR-141/200a in LnCAP cells using specific miRNA inhibitors (anti-miRs) elevated the expression of GNA13 and enhanced the basal invasion of these cells. These data provide strong evidence that GNA13 expression is regulated by post-transcriptional mechanisms involving miR-182 and miR-200 family members. Further studies are being performed to identify the role of these miRNAs in cancer progression and to determine the importance of impact on GNA13 expression as an important mediator of this effect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-278. doi:1538-7445.AM2012-LB-278
Total Electrical Alternation in Pericardial Disease
Authors: DAVID LITTMANN, DAVID H. SPODICK
Journal: Circulation (1958)

Simultaneous electrical alternation of atrial and ventricular components can occur in malignant and sometimes tuberculous pericardial disease and is due, apparently, to a rotary pendular movement of the heart at a rate that differs from the pulse. This oscillation occurs only during effusion with tamponade and clears with paracentesis. It is thought to be the result of unusual freedom or release from the normal pulmonary and thoracic restraints.
To Wrap or Not
Authors: Steven L. Lee
Journal: JAMA Surgery (2013)

McAteer and colleagues1 use the Pediatric Health Information System database to evaluate factors associated with progression to antireflux procedures (ARPs) in children hospitalized for gastroesophageal reflux disease (GERD). Theydemonstrated that children younger than 2 months are more likely to undergo ARPs compared with older children. Furthermore, childrenwith additional comorbidites are more likely to undergo ARPs. These findings are not new and are expected within the pediatric surgical community. Buriedwithin this report is the true controversy regarding the management of GERD in children. Physiologic reflux/ regurgitation iscommonin infantsand,giventime,asignificant proportion of childrenwill simply outgrow their reflux symptoms. The authors point out that no uniformworkupwas performedbefore theoperative intervention.Furthermore, the indicationsforARPsvaried.Thus,theauthors logicallymakeaplea for standardization of theworkup and indications for ARPs in children todeterminewhich children reallyneedoperative interventionvs time tooutgrow their symptoms.Unfortunately, thisstudydoesnothingtoaddressthosepleasforstandardmedicalmanagement andworkup before proceedingwith ARPs. Given that an ARP remains one of the most common operationsperformedbypediatric surgeons, I amperplexed that a standard workup and clear indications for such procedures in childrendonot exist as theydo inadults.One reason for this difference is that children with GERD typically present with feeding problems and have additional comorbidities that influence the need for an ARP. It is common to see a newborn with severe cardiac disease and minimal physiologic reserve who cannot tolerate oral feedings. Should only a gastrostomy tube be inserted, with the risk of aspiration and even death given the patient’s fragile state, or should an ARP be performed (despite no clinical evidence of GERD) in addition to the gastrostomy tube? Another common scenario is a newbornwithneurologic compromisewhoonly tolerates continuous feedings via a postpyloric feeding tube.Oral/gavage feedings result inemesiswithoccasional apneaandcyanotic spells. How long should this patient remain in the hospital and be treated medically to determine whether he or she will outgrowthesesymptoms?Should thesurgeonrecommendanARP to facilitate discharge from the hospital and to prevent future complications (eg, aspirationpneumonia)?Areadditional studies required in either patient to make these decisions? As demonstrated above, care of children with GERD is complex and involves many different factors. Although the authors recognize the ongoing controversy in the management of GERD in infants and children, the data reported in this study are derived from an administrative database that simply does not provide enough details to make any significant conclusions.
Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse Brain
Authors: Alessandro Ieraci, Daniel G Herrera
Journal: PLoS Medicine (2006)

Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occurring in the first two postnatal weeks in mice. Administration of a single dose of ethanol in 7-d postnatal (P7) mice triggers activation of caspase-3 and widespread apoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observed in human FAS. The present study was aimed at determining whether nicotinamide may prevent ethanol-induced neurodegeneration.P7 mice were treated with a single dose of ethanol (5 g/kg), and nicotinamide was administered from 0 h to 8 h after ethanol exposure. The effects of nicotinamide on ethanol-induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzed by Western blot (n = 4-7/group). Density of Fluoro-Jade B-positive cells and NeuN-positive cells was determined in the cingulated cortex, CA1 region of the hippocampus, and lateral dorsal nucleus of the thalamus (n = 5-6/group). Open field, plus maze, and fear conditioning tests were used to study the behavior in adult mice (n = 31-34/group). Nicotinamide reduced the activation of caspase-3 (85.14 +/- 4.1%) and the release of cytochrome-c (80.78 +/- 4.39%) in postnatal mouse forebrain, too. Nicotinamide prevented also the ethanol-induced increase of apoptosis. We demonstrated that ethanol-exposed mice showed impaired performance in the fear conditioning test and increased activity in the open field and in the plus maze. Administration of nicotinamide prevented all these behavioral abnormalities in ethanol-exposed mice.Our findings indicate that nicotinamide can prevent some of the deleterious effects of ethanol on the developing mouse brain when given shortly after ethanol exposure. These results suggest that nicotinamide, which has been used in humans for the treatment of diabetes and bullous pemphigoid, may hold promise as a preventive therapy of FAS.
THE SECRETS OF HOSPITAL PATIENTS.
Authors: EDMUND ANDREWS
Journal: JAMA (1899)

Is the surgeon or physician bound to preserve the secrets of his patients in hospital, as he does of those in private practice? If so, how can he give clinical instruction over them? Then again, other queries arise. If clinical interests can invade the privacy of a patient's condition and divulge his secrets before the class, how about other interests? Have patients in public hospitals no rights to privacy of any kind? For instance, a patient has entered the hospital for an injury in a railway accident, and may have claims on the road for damages. The attorney of the road asks for a statement of the injuries, without bringing any permission from the patient. In a similar way the agent of an accident insurance company wants information, and often boldly claims that the surgeon is not bound to secrecy as to anything happening in a public hospital. Finnally, newspaper