tbuckley/cabot-search huggingface dataset:
Transport kinetics of amino acids across the resting human leg.
Authors: K Lundholm, K Bennegård, H Zachrisson, F Lundgren, E Edén, A C Möller-Loswick
Journal: Journal of Clinical Investigation (1987)

Flux rates of amino acids were measured across the leg after an overnight fast in resting human volunteers. A balanced amino acid solution was, after a primed infusion, continuously infused for 2 h at each of three step-wise and increasing rates corresponding to 8.3, 16.7, 33.2 mg N/kg per h that were equivalent to 0.2, 0.4, 0.8 g N/kg per d. Flux of amino acids across the leg was compared with the flux of glucose, glycerol, lactate, free fatty acids, and oxygen. The size of the muscular tissue pool of amino acids was measured. Whole body amino acid oxidation was estimated by means of the continuous infusion of a 14C-labeled mixture of amino acids. Arterial steady state levels were obtained for most amino acids within 30 to 45 min after the primed constant infusion. Leg flux of amino acids switched from a net efflux after an overnight fast to a balanced flux between infusion rates corresponding to 0.2-0.4 g N/kg per d. At 0.8 g N/kg per d essentially all amino acids showed uptake. The infusion of amino acids stimulated leg uptake of glucose and lactate production and decreased FFA release. Oxygen uptake and leg blood flow increased significantly with increased infusion of amino acids. There was significant variability in transport rate among individual amino acids. Branched chain amino acids showed rapid transport and methionine slow transport rate. Only small changes in the muscle tissue concentration of certain amino acids were registered after 6 h of amino acid infusion despite uptake for several hours. When amino acids were infused at a rate corresponding to 0.8 g N/kg per d, the leg uptake of amino acids was 6% and the simultaneous whole body oxidation of infused amino acids was approximately 10%. Net uptake of leucine across the leg per hour was 62% of the muscle pool of free leucine when amino acids were infused at a rate corresponding to 0.4 g N/kg per d. Multiple regression analysis showed that the arterial concentration of an amino acid was the most important factor for uptake, more so than insulin concentration and blood flow. It is concluded that leg exchange of amino acids is large enough to rapidly change the pool size of the amino acids in skeletal muscle, if not counter-regulated by changes in rates of protein synthesis and degradation. Estimates of the capacity for protein synthesis and transfer RNA acceptor sites in muscles agree in order of magnitude with the net uptake of amino acids at high infusion rates of amino acids. Therefore, measurements of the balance of tyrosine, phenylalanine, and particularly methionine at steady state may reflect net balance of proteins across skeletal muscles even in short-time experiments.
SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts
Authors: V Visconte, H Makishima, A Jankowska, H Szpurka, F Traina, A Jerez, C O'Keefe, H J Rogers, M A Sekeres, J P Maciejewski, R V Tiu
Journal: Leukemia (2011)
Rectal examination in general practice
Authors: N. O Thomson
Journal: BMJ (1990)

Between May 1987 and February 1990 basic or advanced life support, or both, was started on 386 occasions.Ventricular fibrillation was the initial rhythm in 133 cases, and in 25 of these the patient was discharged from hospital.Asystole or electromechanical dissociation was the initial rhythm in 229 cases, and the patient left hospital alive in only two of these cases.Though we are aware that our results and those of Dr Wright and colleagues are similar to those of other European series, we are concerned that they do not approach the 25-30% rate of discharge from hospital consistently reported in North American centres after ventricular fibrillation outside hospital.2We are also surprised at the large propor- tion of patients who are asystolic when the ambulance crew arrives.The initial recorded rhythm of cardiac arrest in Seattle is ventricular fibrillation in three quarters of cases,2 and similar figures have been reported in Brighton.3Rowley et al reported that two thirds of patients with cardiac arrest in Nottingham were in ventricular fibrillation when ambulance crews started resuscitation.' Yet only 38% of the Yorkshire patients and 34-4% of our patients were in ventricular fibrillation.A recent survey from Torbay reports a figure of only 31%.5These differences may simply reflect differences in data collection or criteria for commencing resuscitation.We believe, however, that other factors may be contributing, including the public's lack of knowledge of basic life support skills, unwillingness to perform cardiopulmonary resus- citation, and poor education regarding the signs of cardiac arrest, which leads to slower activation of the emergency services.
Decreased Insulin Binding to Lymphocytes from Diabetic Subjects
Authors: Jerrold M. Olefsky, Gerald M. Reaven
Journal: Journal of Clinical Investigation (1974)

We have studied insulin binding to circulating lymphocytes isolated from 20 untreated adult, nonobese, nonketotic, diabetic subjects with fasting hyperglycemia, 20 normal subjects, and four patients with fasting hyperglycemia secondary to chronic pancreatitis. The results of these studies show that lymphocytes from diabetic patients have decreased ability to specificity bind insulin when compared to lymphocytes from normal subjects. For example, when lymphocytes from diabetic patients and a trace amount of [125I]insulin (3.3 × 10-11 M) were incubated, binding was less than 50% of the value obtained with lymphocytes from normal subjects (2±0.2% vs. 4.2±0.4%). Furthermore, the data show that lymphocytes from diabetic patients have only 1,200 insulin receptor sites per cell compared to 2,200 sites per cell for lymphocytes from normal subjects. Competitive inhibition studies using unlabeled insulin indicate that the affinity for insulin of lymphocytes from both groups is comparable. Consequently the decreased insulin binding of diabetics' lymphocytes is primarily due to a decreased number of available receptors rather than decreased binding affinity. This decreased insulin binding is not due to chronic hyperglycemia since insulin binding to lymphocytes, obtained from four patients with fasting hyperglycemia secondary to chronic pancreatitis, was completely normal. The possibility that some factor present in the plasma of diabetic patients could cause decreased insulin binding also seems unlikely since we could demonstrate no in vitro effects of diabetics' plasma on insulin binding. Lastly, the proportion of lymphocytes which were thymus derived and bone marrow derived were the same in each of the study groups indicating that differences in lymphocyte subpopulations do not account for our results.
Vorapaxar in Patients With Diabetes Mellitus and Previous Myocardial Infarction
Authors: Matthew A. Cavender, Benjamin M. Scirica, Marc P. Bonaca, Dominick J. Angiolillo, Anthony J. Dalby, Mikael Dellborg, Joao Morais, Sabina A. Murphy, Ton Oude Ophuis, Michal Tendera, Eugene Braunwald, David A. Morrow
Journal: Circulation (2015)

Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis.We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P<0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60-0.89]; P=0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07-2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67-0.93]).In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.
A5.4 Repression of wolf-hischhorn syndrome candidate-1 (WHSC1) contributes to osteoarthritis-inducing cartilage loss of functions
Authors: F Espinoza, Y M Pers, P Chuchana, J M Brondello, C Jorgensen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) is the most common degenerative articular disease and is strongly related to age. Ageing is a source of epigenetic changes that could explain the loss of homeostasis of articular chondrocytes leading them to a terminally hypertrophic/senescence phenotype in OA. The hystone methyltransferase WHSC1 (also known as NSD2 or MMSET) methilates lysine 36 of histone 3 and in this way exerts fine tuning of gene expression. An alteration on WHSC1 expression leads to pitfalls in cartilage formation as it has been reported in Wolff Hirschorn Syndrome, a multicomplex congenital syndrome due to deletion of WHSC1 gene. Furthermore, it has been shown abnormalities in cartilage development in a mouse model with haploinsufficiency of WHSC1 and in zebrafish analysis. The aim of this study is to investigate the role and the regulation of the histone H3K36Me2 methyltranferase, WHSC1 (NSD2/MMSET), on cartilage loss of functions in OA. <h3>Materials and Methods </h3> We used primary human OA chondrocytes, specific siRNA interference, western-blot, transient transfection, IL-1b treatment, RT-qPCR, Elisa and statistical analysis. <h3>Results</h3> We found that WHSC1 mRNA expression is reduced in OA senescent-like cartilage compared to healthy donors. WHSC1 mRNA and protein levels are as well reduced in human primary chondrocytes following IL-1b chronic treatment and overexpressing Notch pathway. By a loss of function experiment based on specific siRNA against WHSC1, we found an up-regulation of MMP1, MMP13 and ADAMTS5 mRNA accumulation but not pro-inflammatory cytokines (IL-8, IL-6) in primary chondrocytes. As result, WHSC1-depleted chondrocytes show a reduction expression of Aggrecan and an increase production in GAG. <h3>Conclusion</h3> Our preliminary data demonstrate that WHSC1 is decreased in Osteoarthritis. The downregulation of this epigenetic regulator impacts cartilage homeostasis by decreasing a major anabolic component of extracelular matrix, Aggrecan, and by increasing hypertrophic‐associated matrix‐remodelling factors. Further experiments are required for understanding changes on histone H3 methylation profile induced by this WHSC1 loss of function.
The effects of PGF<sub>2</sub>α, PGI<sub>2</sub>, and TXB<sub>2</sub> on human CFU‐C in healthy and leukemic patients
Authors: Samuel Gross, Diana A. Worthington‐White
Journal: American Journal of Hematology (1984)

Abstract This study was undertaken to test the effects of certain arachidonate derivatives, PGF 2 α, PGI 2 and TxB 2 on in vitro bone marrow granulocyte colony growth (CFU‐C) in leukemia patients receiving maintenance chemotherapy and in normal controls. The addition of PGF 2 α did not result in increased numbers of colonies, but it did cause a shift in the size of the colonies so that there was a significant increase in larger colonies (P &lt; 0.001) and significantly fewer small colonies (P &lt; 0.05) as compared to untreated samples. Of the prostenoids tested in a Tris‐buffered system, PGI 2 affected the greatest increase in CFU‐C (P &lt; 0.01) followed by PGF 2 α (P &lt; 0.05) whereas 6‐keto‐PGF 1 α (the stable hydrate of PGI 2 ) did not affect colony growth. Time‐response curves revealed a linear growth pattern for PGF 2 α with a peak at 10 days, whereas there was a 6‐day growth lag with PGI 2 followed by linear growth with a peak at 13 days. TxB 2 added to cultures significantly reduced the number of bone marrow CFU‐C at all doses tested. The prostanoid effects on CFU‐C derived from leukemic patients on maintenance chemotherapy and from normal individuals were identical in every respect.
What’s in a Name
Authors: Jerry P. Palmer, Irl B. Hirsch
Journal: Diabetes Care (2003)

Shortly after the original description of islet cell antibodies (ICAs) as a marker for childhood type 1 diabetes, it was realized that some adult-onset patients are also ICA positive (1). With the discovery of GAD antibodies as another marker of type 1 diabetes, Paul Zimmet et al. (2) introduced the term “latent autoimmune diabetes of adults” (LADA) to describe an important minority of adult-onset patients with diabetes. Typical patients are positive for GAD antibodies, 35 years of age or older, nonobese, and present without ketoacidosis and weight loss. Although many maintain good glycemic control for several years with sulfonylureas, these patients become “insulin dependent” more rapidly than antibody-negative type 2 diabetic patients (2).

Unfortunately, the phenotype of adult-onset diabetic patients, including their presentation, is extremely variable, resulting in confusion with the nomenclature and classification of these patients. Besides LADA, these patients have been named type 1.5 diabetes, “slowly progressive type 1 diabetes,” “latent type 1 diabetes,” “youth-onset diabetes of maturity,” and even LADA-type 1 and LADA-type 2 (3). How should these patients be classified?

A major question facing the diabetes community is whether all autoantibody-positive diabetes is due to the same pathophysiological disease process. Is autoimmune diabetes in adults due to the same underlying disease process as childhood type 1 diabetes? Or do some patients with autoimmune diabetes in adulthood have a distinct form of autoimmune diabetes compared with classic childhood type 1 diabetes? Phenotypically there are at least three separate populations of autoimmune diabetes in adults: LADA, adult-onset type 1 diabetes, and obese phenotypic type 2 diabetes in patients who are antibody positive.

In this issue of Diabetes Care , Hosszufalusi et al. (4) compared patients with LADA with patients presenting with classic type 1 diabetes at older ages. These populations were also compared with a control group …
Prescribing for older people
Authors: James C Milton, Ian Hill-Smith, Stephen H D Jackson
Journal: BMJ (2008)

#### Summary points

About a fifth of the population in the United Kingdom is 60 years or older,1 yet people in this age group receive 59% of dispensed prescriptions and account for more than half of NHS drug costs.2 Older people often have several coexisting medical problems and take multiple drugs. Increasing age is associated with changes in pharmacokinetics and pharmacodynamics, so prescribing in this age group can be problematic.3

Many randomised controlled trials involving older patients focus on managing a single disease state, such as hypertension or osteoporosis, but people in this age group often have many interacting conditions and are taking many drugs, so guidance on their treatment often has to be based on consensus and involves extrapolating data derived from healthier patients. This review highlights some of the difficulties in prescribing in older patients and offers guidance for appropriate prescribing.

We searched the National Library for Health, PubMed, and Embase databases using the keywords “elderly” and “prescribing”, including synonyms by the MeSH or major descriptor headings. Our search was limited to studies undertaken in humans that were published in English during the past five years. We displayed abstracts of interest using Abstract Plus before obtaining the full text of articles of interest. In addition, we searched the Cochrane Library and our own personal archives of references

### Pharmacokinetic and pharmacodynamic changes

With age the body undergoes several changes that can affect the distribution, metabolism, and excretion of drugs. These …
Acetylcysteine and contrast agent-associated nephrotoxicity
Authors: Carlo Briguori, Fiore Manganelli, Pierfranco Scarpato, Pietro Paolo Elia, Bruno Golia, Guido Riviezzo, Stefano Lepore, Mariateresa Librera, Bruno Villari, Antonio Colombo, Bruno Ricciardelli
Journal: Journal of the American College of Cardiology (2002)
ALTERED SKIN REFLECTANCE IN PATIENTS WITH EPITHELIOMA
Authors: L. BALUŞ, A. CIUREŞ, E. HARAP, D. CERNICANU
Journal: British Journal of Dermatology (1968)

SUMMARY. The reflectance of monochromatic light projected on to 2 skin areas, one chronically exposed to sunlight (forehead) and the other shielded from it by clothing (buttock) has been determined in a group of patients suffering from epitheliomas of the face and in a control group. The forehead/buttock reflectance ratio (c) was computed and found to be significantly increased within the wavelength range from 480 578 nm in subjects with epitheliomas. These results reveal the existence in the skin of these patients of some as yet unknown morphological changes. The occurrence of these changes may be the expression of a predisposition to cancer related to an altered absorption of sunlight by the skin of patients with epitheliomas.
Role of psychological factors
Authors: T. R Nicholson, R. A Kanaan, S. Wessely
Journal: BMJ (2009)

In their review of the management of painful bladder syndrome Marinkovic and colleagues highlight the syndrome as a common and debilitating set of urological symptoms lacking explanatory cystoscopic abnormalities.1 They document its strong association with sexual abuse, fibromyalgia, chronic fatigue syndrome, and, strikingly, a 100-fold increased risk of …
Intrinsic risk factors and the effects of prophylactic bracing on the development of patellofemoral pain in male subjects
Authors: D Van Tiggelen, S Cowan, Y Thijs, P Coorevits, E Witvrouw
Journal: British Journal of Sports Medicine (2011)

Background The aetiology of patellofemoral pain (PFP) is multifactorial. Patellofemoral bracing can be used as a preventative method in subjects undergoing strenuous training. Objective Individuals with intrinsic risk factors for PFP could be identified to provide them with patellofemoral braces as preventative method. Setting Military cadets undergo a strenuous basic military training (BMT) of 6 weeks. Design A prospective cohort study. Participants 169 male officer cadets volunteered for the study. Intervention 43 subjects were randomly assigned to the intervention group wearing patellofemoral braces during the BMT. Main outcome measurements Peak torque of the knee extensor and flexors, the onset of the VMO and VL, the joint position sense (JPS) of the knee, the range of motion and anthropometrical characteristics were measured. A military physical fitness test (MPFT) was assessed prior to the start of their BMT. Results After BMT less recruits in the brace group developed PFP compared to the control subjects (16.3% vs 33.7%; p=0.042). A delayed onset of the VMO-VL, poor JPS, lower peak torque of the knee extensors and a low score on the MPFT were predictive variables in the development of PFP. Conclusion The incidence of PFP in predisposed individuals could be downsised using patellofemoral bracing if intrinsic risk factors are identified. Physical intrinsic risk factors predict the development of PFP during strenuous training sessions. The use of the logistic regression model could identify individuals who could derive benefit from patellofemoral bracing during exacting training sessions.
Lord Lister and the Evolution of Modern Surgery. Glasgow, 1861-1869
Authors: H. C. Cameron
Journal: BMJ (1902)

IT isalmost impossible for the young surgeon of the present day vividly to realize what the state of surgery was thirty-five ..r forty years ago.Surgery before Anti8epsis.The introduction ot ether and chloroform some time pre- viously had initiated great changes.Pain being abolished surgery was robbed of no small part of its terror, and patients, in their anxiety to be restored to health, submitted more willingly to such operations as were recommended for tbeir cure.In this way no doubt a great impetus was given to the surgical art.New operations were devised and employed, while those which were old and well established were resorted to in a larger number of cases.And so, uncertain as the healing of wounds had always been, the uncertainty and dis- appointment which dogged the footsteps of the surgeon became increasingly greater as the scope of surgery was extended.In almost all wounds, whether inflicted by the surgeon or by aucident, inflammation and suppuration were expected as a matter of course.And these things were only the beginning of evil.No matter what skill and care had been expended on the making and dressing of the wound, the issue was necessarily looked forward to with doubt and anxiety.Few of those who did recover did so without serious *episodes and complications of some sort.All suffered from p-in and fever more or less pronounced, and very many only reached the terra firma of restored health by swimming through weeks or months of severe and painful illness.Secondary haemorrhage, tetanus, erysipelas, septicaemia, pyaemia, and hospital gangrene were never all absent from the hospital wards, and at times pyaemia and hospital gan- grene became alarmingly epidemic.In the absence of any certain knowledge of the real mode of causation of these wound-begotten diseases, and, therefore, of any sure means of avoiding their occurrence, the surgeon felt no real personal responsibility regarding them, whatever grief and disappoint- ment he might experience when his best efforts repeatedly eaded in disaster and failure.When his patients were-deci- mated and his heart was well-nigh broken by these terrible visitants, he received the sympathy of his friends and pupils.He had done his work well, and a hail in harvest had come ti) destroy it.He was in no waV to blame.He was a man beset by misfortune.This was very much the state of matters in the Glasgow Royal Infirmary, at that time the only General Hospital in the c ty, when in i861 Lord Lister (then Mr. Lister, a young man of 34) was elected one of its surgeons.He had been made
A Window of Opportunity
Authors: Sandra J. Bliss, Richard H. Moseley, John Del Valle, Sanjay Saint
Journal: New England Journal of Medicine (2003)

In this Journal feature, information about a real patient is presented in stages (boldface type) to expert clinicians from several specialties, who respond to the information, sharing their reasoning with the reader (regular type). The authors' commentary follows.A 62-year-old woman presented to her local emergency department because of pain in the epigastrium and right upper quadrant. The pain had begun insidiously five days earlier and was constant, severe, and exacerbated by deep inspiration. She also reported having anorexia, nausea, fatigue, night sweats, and chills, but not fever, vomiting, diarrhea, melena, hematochezia, jaundice, or weight loss.Several features of the patient's history are useful in formulating a focused differential diagnosis of acute abdominal pain. The pain of acute cholecystitis commonly localizes to both the epigastrium and the upper abdomen, peptic ulcer disease and acute pancreatitis frequently . . .