tbuckley/cabot-search huggingface dataset:
The haematuria clinic
Authors: P Marazzi, R Gabriel
Journal: BMJ (1994)

engineer then specific sources ought to be either identified or excluded.If this procedure fails then consultant neuro- audiological investigations ought to be carried out to exclude a physiological cause.If these time consuming and expensive procedures fail it is usually very difficult to come up with an explanation despite there being little doubt about the distress being caused.No doubt further research will be carried out, but probably each case will prove to be as different and as individual as the complainants themselves.
Suboptimal Monitoring and Dosing of Unfractionated Heparin in Comparative Studies with Low-Molecular-Weight Heparin
Authors: Robert Raschke, Jack Hirsh, James R. Guidry
Journal: Annals of Internal Medicine (2003)

Site-specific validation of the activated partial thromboplastin time (aPTT) therapeutic range is required to ensure administration of the optimal dose of unfractionated heparin. Therapeutic ranges of 1.5 to 2.5 times the control value are subtherapeutic for most modern aPTT reagents.To audit the appropriateness of aPTT monitoring in clinical trials comparing unfractionated heparin and low-molecular-weight heparin in patients with venous thromboembolism.Search of PubMed database from 1984 to 2001.Randomized, controlled trials that compared unfractionated and low-molecular-weight heparin for the treatment of venous thromboembolism.Use of unvalidated and potentially suboptimal therapeutic ranges for aPTT in patients assigned to receive unfractionated heparin.Fifteen studies met inclusion criteria. Only 3 studies used a validated aPTT therapeutic range, and 11 studies used a range that included aPTT values 1.5 times the control value. Ten studies reported unfractionated heparin doses, and 7 of these documented a reduction to less than 30 000 U/d in response to aPTT results.Most studies monitored unfractionated heparin inappropriately. This shortcoming could be responsible for the reduced efficacy of unfractionated heparin in clinical trials.
Thromboxane synthase regulates the migratory phenotype of human glioma cells
Authors: Alf Giese, Christian Hagel, Ella L. Kim, Svenja Zapf, Jasmin Djawaheri, Michael E. Berens, Manfred Westphal
Journal: Neuro-Oncology (1999)

The capacity of glial tumor cells to migrate and diffusely infiltrate normal brain compromises surgical eradication of the disease. Identification of genes associated with invasion may offer novel strategies for anti-invasive therapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, has been identified by differential mRNA display as being overexpressed in a glioma cell line selected for migration. In this study TXsyn mRNA expression was found in a large panel of glioma cell lines but not in a strain of human astrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glial tumors and in reactive astrocytes, whereas it could not be detected in quiescent astrocytes and oligodendroglia of normal brain. Glioma cell lines showed a wide range of thromboxane B2 formation, the relative expression of which correlated with migration rates of these cells. Migration was effectively blocked by specific inhibitors of TXsyn, such as furegrelate and dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were less effective. Treatment with specific inhibitors also resulted in a decrease of intercellular adhesion in glioma cells. These data indicate that TXsyn plays a crucial role in the signal transduction of migration in glial tumors and may offer a novel strategy for anti-invasive therapies.
Operation for Angina Pectoris
Authors: H. D. Friedberg, W. D. Johnson, G. F. D'Cunha
Journal: BMJ (1968)

BmsIM 57 aemia occurs in a number of conditions, such as the nephrotic syndrome and familial xanthomatosis, which are too lethal or too rare to be of importance in the aetiology of coronary artery disease.Myxoedema is often considered to be rare.However, thyroid antibodies may be found in over 10% of the population.The work of Bastenie and his associates suggests that hypertension, obesity, and coronary artery disease are often associated with a focal atrophic thyroiditis and thyroid antibodies.3"Hypercholesterolaemia can occur in autoimmune thyroiditis before there is any other evidence of impaired thyroid function.'Further study (unpub- lished) hats confirmed that this hyperchalesterolaemia may precede other manifestations of thyroid deficiency by years.This stage of premyxoedema may play an important role in the aetiology of coronary artery disease.(It must be remembered that serum cholesterol levels are depressed by inflamma- tion and anaemia, so that values obtained after a myocardial infarction or in anaemic myx- oedematous patients may be misleading.)Members of those families with autoimmune thyroiditis who are protected by oestrogens and other factors may be saved from coronary artery disease and develop myxoedema.The importance of the role of autoimmune thyroiditis in coronary artery disease can only be assessed by further study.-Iam, etc.,
Characterization of a non-T, non-B human lymphocyte (L cell) with use of monoclonal antibodies. Its regulatory role in B lymphocyte function.
Authors: P I Lobo
Journal: Journal of Clinical Investigation (1981)

These studies investigate the role of L lymphocytes in regulating terminal B lymphocyte differentiation. L cells have abundant Fc IgG receptors and comprise 10--15% of human peripheral blood mononuclear cells (PBMC). L cells lack the conventional markers of B and T lymphocytes and in culture, do not develop into B cells, T cells, or macrophages. Additionally, use of monoclonal antibodies failed to detect on L cells, surface antigens specific for B cells, T cells, and macrophages. In these studies, purified L cell subpopulations depleted of macrophages were co-cultured with autologous PBMC in the presence of pokeweed mitogen and at the end of 8 d, development of intracytoplasmic immunoglobulin (Ig) was determined. L cells were depleted of B and T cells by rosetting techniques and, in addition, by cytotoxicity techniques using monoclonal-specific antisera to T cells. In 14 individuals, L cells when co-cultured with PBMC, enhanced Ig synthesis by 83% +/- 62 SD, and also enhanced cell proliferation. Radiated L cells lost enhancing properties. To study the role of their high density Fc IgG receptors, L cells pretreated with IgG antibody-sensitized erythrocytes were used (i.e., after lysis of rosettes). Such L cells significantly inhibited Ig synthesis (by greater than 50%) despite promoting cell proliferation. Antibody-sensitized erythrocyte-rosetted macrophages did not inhibited Ig synthesis. Thus, positive and negative influences can be mediated by the same cell, depending on the state of Fc-receptor stimulation. Such cells may play a more prominent role in "feed-back" regulation of Ig synthesis by virtue of having abundant Fc IgG receptors.
Molecular Basis of Proteinuria of Glomerular Origin
Authors: Barry M. Brenner, Thomas H. Hostetter, H. David Humes
Journal: New England Journal of Medicine (1978)

THE process of urine formation begins at the walls of the glomerular capillaries with the separation of as much as a third of the plasma entering the glomeruli of each kidney into a solution having the properties of a nearly ideal ultrafiltrate. Driven by a hydraulic force created by the pumping action of the heart, ultrafiltrate flows across these capillary walls at an enormous rate, when considered in biologic terms, exceeding by at least two orders of magnitude that across other membranes studied thus far.1 Despite their extremely low intrinsic resistance to the flow of water, however, these same glomerular . . .
Management of the Obstructed Airway
Authors: Joseph S. Redding
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The COMMENTARY by Gann contains some surprising statements that may be misleading. In discussing the recommendations of the EMS Committee on management of foreign-body airway obstruction he states: The two largest sets of data on the efficacy of the recommended procedures have been compiled by the American Heart Association (AHA) and by Henry Heimlich, MD. (Only the unpublished data of the AHA have been available to the NAS. These may be obtained from Royce Britton, American Heart Association, 7320 Greenville Ave, Dallas, TX 75231.) The AHA survey of several hundred cases of airway obstruction points out that all recommended procedures have been found to be successful in varying degrees: the survey indicates a success rate of about 50% in those cases in which the back blow procedure was used, about 85% success using the manual-thrust procedure, and about 55% success using the finger-probe procedure. In the spring
Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials
Authors: T. Vilsboll, M. Christensen, A. E. Junker, F. K. Knop, L. L. Gluud
Journal: BMJ (2012)

To determine whether treatment with agonists of glucagon-like peptide-1 receptor (GLP-1R) result in weight loss in overweight or obese patients with or without type 2 diabetes mellitus.Systematic review with meta-analyses.Electronic searches (Cochrane Library, Medline, Embase, and Web of Science) and manual searches (up to May 2011). Review methods Randomised controlled trials of adult participants with a body mass index of 25 or higher; with or without type 2 diabetes mellitus; and who received exenatide twice daily, exenatide once weekly, or liraglutide once daily at clinically relevant doses for at least 20 weeks. Control interventions assessed were placebo, oral antidiabetic drugs, or insulin.Three authors independently extracted data. We used random effects models for the primary meta-analyses. We also did subgroup, sensitivity, regression, and sequential analyses to evaluate sources of intertrial heterogeneity, bias, and the robustness of results after adjusting for multiple testing and random errors.25 trials were included in the analysis. GLP-1R agonist groups achieved a greater weight loss than control groups (weighted mean difference -2.9 kg, 95% confidence interval -3.6 to -2.2; 21 trials, 6411 participants). We found evidence of intertrial heterogeneity, but no evidence of bias or small study effects in regression analyses. The results were confirmed in sequential analyses. We recorded weight loss in the GLP-1R agonist groups for patients without diabetes (-3.2 kg, -4.3 to -2.1; three trials) as well as patients with diabetes (-2.8 kg, -3.4 to -2.3; 18 trials). In the overall analysis, GLP-1R agonists had beneficial effects on systolic and diastolic blood pressure, plasma concentrations of cholesterol, and glycaemic control, but did not have a significant effect on plasma concentrations of liver enzymes. GLP-1R agonists were associated with nausea, diarrhoea, and vomiting, but not with hypoglycaemia.The present review provides evidence that treatment with GLP-1R agonists leads to weight loss in overweight or obese patients with or without type 2 diabetes mellitus.
Development of novel combinations of targeted and immunotherapies by understanding immune resistance using a high throughput assay of T cell mediated cytotoxicity
Authors: Shruti Malu, Rina Mbofung, Jahan Khalili, Nikunj Satani, Marie-Andrée Forget, Cara Haymaker, Florian Muller, Chantale Bernatchez, Laszlo Radvanyi, Patrick Hwu
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The ability of the immune system to treat established tumors is very well recognized. Immunotherapeutic approaches such as Adoptive T cell therapy and anti-CTLA-4 antibody treatment can result in long-term responses in some patients with metastatic melanoma. However, the majority
<i>Helicobacter pylori</i>DNA's anti-inflammatory effect on experimental colitis
Authors: Stephanie Y. Owyang, Jay Luther, Christopher C. Owyang, Min Zhang, John Y. Kao
Journal: Gut Microbes (2012)

Our laboratory has demonstrated a clinical inverse association between H. pylori infection and inflammatory bowel disease (IBD). In our most recent work we described a possible mechanism by which H. pylori can reduce the risk of developing IBD. Specifically, we were able to demonstrate the immuno-regulatory properties of the H. pylori genome and its ability to downregulate inflammatory responses through interaction with mucosal dendritic cells both in an in vitro and in vivo model. Furthermore, we were able to demonstrate the ability of H. pylori DNA to downregulate dendritic cell production of IL-12 and type I interferon, two pro-inflammatory cytokines. In the present work, we conducted further studies to examine the unique properties of the H. pylori genome and the exact mechanism through which it interacts with dendritic cells. Our data highlight a specific immuno-regulatory sequence (IRS), TTTAGGG, which occurs significantly more frequently as compared with other IRS sequences and is unique to the H. pylori genome. Additionally, we illustrate that H. pylori DNA has no effect on modulating the TLR-4 dependent LPS-induction of dendritic cell IL-12 production. This indicates that the inhibitory effect of H. pylori genomic DNA is restricted to the TLR-9 signaling pathway that senses bacterial DNA. In conclusion, the findings of this addendum strengthen the evidence for unique immunoregulatory properties of the H. pylori genome and revealed the importance of TLR-9 mediated mechanism in the pathogenesis of IBD.
Financial donors warn Ugandan government over anti-gay law
Authors: A. Gulland
Journal: BMJ (2014)

<h3>Abstract</h3> The vasodilator neuropeptide calcitonin gene-related peptide (CGRP) plays both detrimental and protective roles in different pathologies. CGRP is also an essential component of the neuro-immune dialogue between nociceptors and mucosal immune cells. We previously reported that CGRP strongly inhibits human immunodeficiency virus type 1 (HIV-1) infection, by suprresing Langerhans cells (LCs)-mediated HIV-1 transfer to T-cells during trans-infection. To understand the requirements for CGRP receptor (CGRP-R) activation during inhibition of HIV-1 transmission, we here investigated the anti-HIV-1 activities of full-length native CGRP and its recently developed stable analogue SAX, as well as several CGRP peptide fragments containing its binding C-terminal and activating N-terminal regions. We show that SAX significantly inhibits LCs-mediated HIV-1 trans-infection but with lower potency than CGRP, while all CGRP peptide fragments tested have no effect. In addition, CGRP readily enters the epithelial compartment of mucosal tissues and does not modify the distribution and density of mucosal immune cells. <i>In-vivo</i>, a single CGRP treatment in humanized mice, before vaginal challenge with high-dose HIV-1, restricts the increase in plasma viral load and maintains higher CD4+ T-cell counts. Together, our results call for the optimization and design of CGRP analogues and agonists, which could be harnessed for prevention of mucosal HIV-1 transmission.
Federal Human Research Oversight of Clinical Trials in the United States
Authors: Deborah A. Zarin, Tony Tse, Jerry Menikoff
Journal: JAMA (2014)

The primary federal human subjects protections (HSP) policies in the United States, including requirements for institutional review board review and informed consent, are the US Food and Drug Administration (FDA) HSP regulations1 and the Common Rule.2 The first covers FDA-regulated clinical investigations of drugs, biologics, and devices, regardless of funding source, whereas the second applies to human studies funded or conducted by 17 federal entities, regardless of the type of intervention studied. These regulations are largely consistent but contain differences. Concerns have been raised about burdens and inefficiencies for studies covered by both regulations (overlap trials),3 and about some studies that are covered by neither (gap trials).4 To inform such discussions, we estimated the numbers of active US-based clinical trials subject to these regulations.
Selective Reduction of Multifetal Pregnancies in the First Trimester
Authors: Richard L. Berkowitz, Lauren Lynch, Usha Chitkara, Isabelle A. Wilkins, Karen E. Mehalek, Emanuel Alvarez
Journal: New England Journal of Medicine (1988)

THE number of pregnancies complicated by multiple gestation has been increasing as a result of the relatively widespread use of ovulatory drugs and in vitro fertilization. In pregnancies with multiple gestations, adverse outcome is directly proportional to the number of fetuses within the uterus, primarily because of an increased predisposition to premature delivery. Although there is a good deal of information about the gestation of twins, there is very little on triplets, and virtually nothing but case reports have been published on pregnancies involving four or more fetuses. It is therefore extremely difficult to counsel patients about the expected outcome . . .
Collagen VII plays a dual role in wound healing
Authors: Alexander Nyström, Daniela Velati, Venugopal R. Mittapalli, Anja Fritsch, Johannes S. Kern, Leena Bruckner-Tuderman
Journal: Journal of Clinical Investigation (2013)

Although a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds.
A<i>PCSK9</i>Missense Variant Associated with a Reduced Risk of Early-Onset Myocardial Infarction
Authors: Sekar Kathiresan
Journal: New England Journal of Medicine (2008)

CasePatients Controls % Finland FINRISK 209 210 1.3 4.1 0.30 (0.11-0.84) 0.02 Sweden Malmö Diet and Cancer Study -cardiovascular cohort 150 149 0.7 2.0 0.32 (0.07-1.61) 0.17 Spain Registre Gironi del Cor (REGICOR) 361 361 1.0 2.8 0.35 (0.15-0.82) 0.02 Seattle Heart Attack Risk in Puget Sound 542 631 0.9 1.9 0.45 (0.21-0.98) 0.
Comment on Okabayashi et al. Intensive Versus Intermediate Glucose Control in Surgical Intensive Care Unit Patients. Diabetes Care 2014;37:1516–1524
Authors: Marina V. Viana, Luciana V. Viana
Journal: Diabetes Care (2014)

Hyperglycemia is a major concern in critically ill patients, especially in surgical patients. The optimal target of glucose control in this population and the best method to achieve this goal in order to avoid hypoglycemia is unknown. Okabayashi et al. (1) demonstrated that intensive glucose control (glucose target 80–110 mg/dL) compared with intermediate glucose control (glucose target 140–180 mg/dL) in a selected group of patients who underwent hepato-biliary-pancreatic surgery was feasible using a closed-loop glycemic sensor, without hypoglycemic events and, more important, with a decreased number of surgical site infections and shorter hospitalization length. The result of this trial reinforces the need for new trials using …
Duodenogastric reflux and pyloric surgery.
Authors: C D MacLean
Journal: BMJ (1972)

glucose tolerance,3 which this patient had.Pantothenic acid has been used for the treatment of postoperative intestinal atony.'This patient was said to 'have hia iany episodes of abdominal distension."In pantothenic acid deficiency alphaglobulin levels are in- creased.3This patient had raised alpha-l and alpha-2 globulin levels.Pantothenic acid deficiency can produce upper abdominal pain and an increased susceptibility to infectious diseases of the respiratory tract.1These were particular features of this patient's case.She was said to have had several episodes of "an acute abdomen" in her last weeks of life and died with acute bronchitis, bronchopneumonia, herpes of the mouth and nose, and other terminal infections.As pantothenic acid is widely distributed in nature, its administration is often not con- sidered important.However, it is unstable, and as folic acid and biotin are apparently required for its utilization2 perhaps it should be given to folate deficient subjects.-Iam, etc.,
Thyroid function in fetuses with chromosomal abnormalities.
Authors: J G Thorpe-Beeston, K H Nicolaides, C M Gosden, A M McGregor
Journal: BMJ (1991)

During treatment with inhaled beclomethasone the osteocalcin concentrations decreased, as has been observed in patients taking oral corticosteroids. This might imply that during beclomethasone treatment bone formation is depressed, which could result in osteoporosis in the long run. In our pilot study we investigated healthy subjects who used a high dose of beclomethasone for a short period of time. Whether osteocalcin concentrations are also lowered in asthmatic patients treated with lower doses of beclomethasone over the long term is unknown at present. This is not unlikely, however?firstly, because the r?sorption of the drug might be better in patients than in healthy subjects and, secondly, because osteocalcin remained depressed during long term treatment of patients with oral corticosteroids.4 There fore a longitudinal study measuring serum osteocalcin concentrations and bone mineral density in newly diagnosed patients with asthma taking inhaled cortico? steroids seems warranted.
Arthritis of Hepatitis Associated with Australia Antigen
Authors: DANIEL K. ONION
Journal: Annals of Internal Medicine (1971)

Three patients presented with rash and polyarthritis as a prodrome of hepatitis. They initially had Australia antigen and depressed complement levels in both synovial fluid and serum. With the onset of clinically apparent jaundice, the arthritis resolved, serum complement returned to normal, and Australia antigen was no longer detectable in the serum. Subsequently, antibody to Australia antigen appeared. These observations are similar to the events in experimental serum sickness and strongly suggest that circulating immune complexes may be responsible for at least the arthritic manifestations of hepatitis associated with Australia antigen.