tbuckley/cabot-search huggingface dataset:
Defective regulation of phosphatidylcholine-specific phospholipases C and D in a kindred with Tangier disease. Evidence for the involvement of phosphatidylcholine breakdown in HDL-mediated cholesterol efflux mechanisms.
Authors: M Walter, H Reinecke, U Gerdes, J R Nofer, G Höbbel, U Seedorf, G Assmann
Journal: Journal of Clinical Investigation (1996)

The negative correlation between coronary heart disease and plasma levels of HDL has been attributed to the ability of HDL to take up cellular cholesterol. The HDL3-induced removal of cellular cholesterol was reported to be impaired in fibroblasts from patients with familial HDL deficiency (Tangier disease, TD). In addition, we have recently shown that HDL3 stimulates the hydrolysis of phosphatidylcholine (PC) in cholesterol-loaded fibroblasts. To investigate whether this cell signaling pathway is involved in cholesterol efflux mechanisms, we compared the HDL3-induced PC hydrolysis in normal fibroblasts and in fibroblasts from a TD kindred, in whom the HDL3- and apolipoprotein A-I (apo A-I)-induced mobilization of cellular cholesterol was found to be reduced by 50%. The HDL3-induced formation of phosphatidic acid (PA) via PC-specific phospholipase D (PC-PLD) was markedly reduced by 60-80% in these cells, whereas the formation of diacylglycerol (DG) via PC-specific phospholipase C (PC-PLC) was two- to threefold enhanced. Defective regulation of PC-PLC and PC-PLD was similarly observed in response to apo A-I and endothelin, but not in response to the receptor-independent stimulation of PC hydrolysis by PMA. A Tangier-like PA and DG formation pattern could be induced in normal cells after preincubation with pertussis toxin, suggesting the involvement of a G-protein. The impaired mobilization of radiolabeled cellular cholesterol in TD cells could completely be overcome by increasing the PA levels in the presence of the PA phosphohydrolase inhibitor propranolol. Conversely, the inhibition of PA formation in the presence of 0.3% butanol as well as the inhibition of DG formation in the presence of the PC-PLC inhibitor D 609 reduced the mobilization of cellular cholesterol both in normal and in TD cells. Our data indicate that the coordinate formation of PA and DG via PC-PLD and PC-PLC is essential for efficient cholesterol efflux. The molecular defect in this TD kindred appears to affect an upstream effector of protein kinase C responsible for the G-protein-dependent regulation of PC-specific phospholipases.
Simultaneous detection of two mechanisms of immune destruction of penicillin‐treated human red blood cells
Authors: Israel Yust, Bertha Frisch, Naomi Goldsher
Journal: American Journal of Hematology (1982)

Abstract Two separate processes of putative red‐cell destruction in penicillin‐induced immune hemolysis were measured simultaneously by a rapid (3 hour) assay utilizing 51 Cr‐labelled red blood cells (RBC). Antibody‐dependent, cell‐mediated cytotoxicity (ADCC) was estimated by release of 51 Cr; and antibody‐dependent phagocytosis (ADPh) by quantitation of 51 Cr uptake into mononuclear phagocytes as well as by counts of engulfed RBC. Attacking cells were obtained by Ficoll‐Hypaque separation of peripheral blood from normal donors. Phagocytosis as well as lysis were proportional to anti‐penicillin antiserum concentration, to incubation time, and to the concentration of the attacking cells. Enrichment of mononuclear phagocytes in the attacking cell population by albumin gradient separation led to an increase in phagocytosis as well as in cytotoxicity. Depletion of mononuclear phagocytes resulted in a decline in both processes. Dilution of antiserum abolished ADCC but affected ADPh only slightly. Iodoacetate as well as colchicine inhibited both activities. These results indicate that both processes may be operative in the immune destruction of RBC in vivo.
PTU-067 Out-patient assessment for liver transplantation: a single centre experience: Abstract PTU-067 Table 1
Authors: T R Lim, M J Armstrong, D D Houlihan, K Wong, C Cook, A Turner, M Perrin, J Cantrill, P Ashcroft, D Hughes, C Weijers, A Holt
Journal: Gut (2012)

<h3>Introduction</h3> Assessment for orthotopic liver transplantation (LT) traditionally requires admission to hospital. In 2010, the liver unit at the University Hospital Birmingham (UHB) launched the first UK-based out-patient assessment programme (OPA). This study aims to describe our experience, with specific focus on feasibility, efficacy, cost-effectiveness and patient satisfaction. <h3>Methods</h3> Patients undergoing elective LT assessment were retrospectively analysed between June 2010 and April 2011. Data collected included patient demographics/clinical features, LT assessment parameters, duration to listing/LT and reasons for LT refusal. An extensive cost evaluation was performed on both in- and out-patient LT assessment, including clinical tests, staffing and hospital facilities utilised. Patient satisfaction questionnaires were collected prospectively from April 2011 to November 2011. <h3>Results</h3> 179 patients underwent LT assessment. 87/94 successfully completed OPA, with seven converted to in-patient LT assessment (IPA) due to pre-existing co-morbidity including refractory ascites and hepatic encephalopathy. All patients referred for OPA were triaged 2 weeks prior to the assessment to ensure suitability. 92 patients successfully underwent IPA. 66/87 OPAs were subsequently listed for LT (median duration from OPA to listing 3 days [0–306], of which 37/66 received a cadaveric graft. The reasons for OPAs not listed include: too early for LT (50.0%), contraindication to LT (42.9%) and patient refusal (7.1%). 53/92 IPAs were listed, mean duration 4 days [1–39], of which 34/53 were transplanted. Reasons for IPAs not listed: contraindication to LT (48.2%), too early for LT (44.4%) and patient refusal (7.4%). A single IPA costs on average £14 441 as compared to £11 494 for an OPA. Overall satisfaction (mean score 9.6/10; 10=very satisfied, 1=very dissatisfied) and convenience (7.9/10) for patients undergoing OPA were high. <h3>Conclusion</h3> We describe for first time that OPA is feasible, efficient and cost-effective. With increasing demand on hospital beds in the UK National Health Service, such a programme has the potential to reduce the burden on LT in-patient services. <h3>Competing interests</h3> None declared.
The International Campaign to Revitalise Academic Medicine
Authors: Crispin Hiley, Andrew Robertson
Journal: Annals of Internal Medicine (2005)

Letters1 March 2005The International Campaign to Revitalise Academic MedicineCrispin Hiley, MB, ChB and Andrew Robertson, MB, ChBCrispin Hiley, MB, ChBFrom Manchester University, Manchester M13 9PL, England, United Kingdom, and Glasgow University, Glasgow, Scotland, United Kingdom.Search for more papers by this author and Andrew Robertson, MB, ChBFrom Manchester University, Manchester M13 9PL, England, United Kingdom, and Glasgow University, Glasgow, Scotland, United Kingdom.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-142-5-200503010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Academic medicine has been in decline over recent years and is facing a crisis in recruitment. In response to this trend, a working party was appointed to coordinate the International Campaign to Revitalise Academic Medicine (1). More than 40 international medical journals, including BMJ and The Lancet, and a number of prominent organizations are supporting this campaign (2). The campaign aims to consult all stakeholders and provide a truly international response to the challenges and opportunities facing academic medicine.Teaching is central to academic medicine, and those who work in this field have traditionally been the educators ...References1. Tugwell P. Campaign to revitalise academic medicine kicks off [Editorial]. BMJ. 2004;328:597. [PMID: 15016665] CrossrefMedlineGoogle Scholar2. Homepage of the International Campaign to Promote Academic Medicine. bmj.bmjjournalscom/academicmedicine. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Manchester University, Manchester M13 9PL, England, United Kingdom, and Glasgow University, Glasgow, Scotland, United Kingdom. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByScientific activity and working hours of physicians in university hospitals: Results from the Innsbruck and Salzburg physician lifestyle assessment (TISPLA) 1 March 2005Volume 142, Issue 5Page: 390-391KeywordsAcademic medicine ePublished: 1 March 2005 Issue Published: 1 March 2005 CopyrightCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Percutaneous Left Atrial Appendage Occlusion (PLAATO) for Preventing Cardioembolism
Authors: Toshiko Nakai, Michael D. Lesh, Edward P. Gerstenfeld, Renu Virmani, Russell Jones, Randall J. Lee
Journal: Circulation (2002)

Background — Atrial fibrillation is associated with a high risk for cardioembolic stroke. The left atrial appendage (LAA) is the source of the vast majority of these thromboemboli. A novel implanted device for percutaneous LAA transcatheter occlusion (PLAATO) has been designed to seal the LAA. The purpose of this study was to test the feasibility and safety of transcatheter LAA occlusion in dogs. Methods and Results — A PLAATO implant was delivered to the LAA through a 12F transseptal catheter in 25 dogs. The PLAATO device was repositioned until occlusion was seen, or it was recaptured and replaced with a different size. LAA sealing was confirmed by intracardiac echocardiography and contrast fluoroscopy. Follow-up was performed 2 days to 6 months after implantation. After imaging assessment, dogs were euthanized and LAA was examined for device healing, migration, perforation, and any thrombosis, both grossly and histologically. The LAA was occluded in all cases. No mobile thrombi associated with the implantation were seen. Healing on the atrial-facing surface was 90% at 1 month and was complete by 3 months, which was confirmed by gross and histological examination. Light microscopic examination of brain, kidney, and spleen showed no evidence of emboli or infarct. Conclusions — Transcatheter LAA occlusion is simple and feasible. At the follow-up study, the device remained in the LAA, with benign healing and no evidence of new thrombus or damage to surrounding structures. This new strategy may provide an alternative treatment for patients with nonvalvular atrial fibrillation who are less than optimal candidates for warfarin.
VALUE OF ROUTINE BLOOD SUGAR TESTS IN THE DETECTION OF DIABETES MELLITUS
Authors: E. P. McCullagh
Journal: JAMA (1953)

For the past 30 years, it has been the practice of our group to perform routine blood sugar tests on all new patients. Because we believe that this is an important method of detecting diabetes, this paper is presented in order to illustrate some of the results we obtained. Our method is advocated for general use in office practice. If all physicians who demand that a complement fixation test for syphilis be performed on all patients would obtain a blood sugar test as well, many cases of early diabetes would be detected. <h3>MATERIALS AND METHODS</h3> This study presents data on the number of new patients in our practice who, solely because the initial blood sugar level was elevated, were later proved to have diabetes. A total of 2,357 consecutive patients entering all services of the diagnostic division of the Cleveland Clinic constitutes the basis of this survey. The majority of
Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion
Authors: Marco Lucioni, Francesca Novara, Giacomo Fiandrino, Roberta Riboni, Daniele Fanoni, Mariarosa Arra, Luigia Venegoni, Marta Nicola, Elena Dallera, Luca Arcaini, Francesco Onida, Pamela Vezzoli, Erica Travaglino, Emanuela Boveri, Orsetta Zuffardi, Marco Paulli, Emilio Berti
Journal: Blood (2011)
Spread of HIV Infection in Married Monogamous Women in India
Authors: Raman R. Gangakhedkar
Journal: JAMA (1997)

<h3>Context.</h3> —A high prevalence of human immunodeficiency virus (HIV) infection in female sex workers (FSWs) and men who attend sexually transmitted disease (STD) clinics poses a risk for spread of infection to other populations. <h3>Objective.</h3> —To examine spread of HIV to a low-risk population by comparing prevalence of, and risk factors for, HIV and STDs in FSWs and non-FSWs. <h3>Methods.</h3> —Women attending STD clinics in Pune, India, were assessed for STDs and HIV from May 13, 1993, to July 11, 1996. Demographic and behavioral information was collected, and clinical and laboratory assessment was performed. <h3>Main Outcome Measure.</h3> —Prevalence and risk determinants of HIV infection. <h3>Results.</h3> —Of 916 women enrolled, 525 were FSWs and 391 were non-FSWs. Prevalence of HIV in FSWs and non-FSWs was 49.9% and 13.6%, respectively (<i>P</i>&lt;.001). In multivariate analysis, inconsistent condom use and genital ulcer disease or genital warts were associated with prevalent HIV in FSWs. History of sexual contact with a partner with an STD was associated with HIV in non-FSWs. <h3>Conclusions.</h3> —Infection with HIV is increasing in non-FSWs, previously thought to be at low risk in India. Since history of sexual contact with their only sex partner was the only risk factor significantly associated with HIV infection, it is likely that these women are being infected by their spouses. This underscores the need for strengthening partner-notification strategies and counseling facilities in India.
Hemodynamic assessment after palliative surgery for hypoplastic left heart syndrome.
Authors: P Lang, W I Norwood
Journal: Circulation (1983)

Ten patients with hypoplastic left heart syndrome underwent cardiac catheterization to assess the effectiveness of palliative surgery designed to prepare them for a modified Fontan procedure. The objectives of palliation were to establish unobstructed systemic blood flow, normalize pulmonary blood flow and pressure, and relieve pulmonary venous obstruction. In the first four patients, systemic blood flow from the right ventricle was established by means of a conduit from either the right ventricular free wall or the proximal main pulmonary artery to the thoracic aorta. Pulmonary blood flow was limited by pulmonary artery banding and ligation of the ductus arteriosus in three patients and by a Blalock-Taussig shunt in one. Conduit obstruction of systemic blood flow developed in two of these infants, and pulmonary vascular abnormalities precluded reparative surgery in the other two. In the other six patients, systemic blood flow was established by direct anastomosis of the proximal main pulmonary artery to the ascending aorta and aortic arch. The pulmonary vasculature was protected by providing pulmonary flow through a central or Blalock-Taussig shunt. The interatrial communication was enlarged by atrial septectomy or balloon atrial septotomy. One infant had progressive tricuspid regurgitation necessitating valve replacement. One, in whom balloon atrial septotomy had been performed, developed an obstructive interatrial communication necessitating late atrial septectomy. These six patients were candidates for physiologic correction. To date, three patients have undergone a modified Fontan procedure; two are clinically well at 9 and 12 months after surgery. Three patients await this procedure.
An evaluation of home visiting of patients by physicians in geriatric medicine
Authors: M. Arcand, J Williamson
Journal: BMJ (1981)

The practice of preadmission home visiting of patients referred to geriatric medicine units has in recent years been criticised as being unnecessary on the grounds that if there is no waiting list there is no need for allocation of priority for admission; as being wasteful of doctors9 time; as being resented by general practitioners; and as failing to provide adequate clinical information. The geriatric medicine department at the City Hospital with no waiting list for patients referred by general practitioners has retained home visits for most referrals because of the advantages in terms of acceptability to general practitioners (98-100%); the quantity and quality of information obtained; the usefulness of this information in deciding appropriate management and in planning discharge from hospital; and the provision of a unique teaching opportunity, which is highly valued by students and teachers alike.
Identification of submicroscopic genetic changes and precise breakpoint mapping in myelofibrosis using high resolution mate‐pair sequencing
Authors: Terra Lasho, Sarah H. Johnson, David I. Smith, John D. Crispino, Animesh Pardanani, George Vasmatzis, Ayalew Tefferi
Journal: American Journal of Hematology (2013)

We used high resolution mate-pair sequencing (HRMPS) in 15 patients with primary myelofibrosis (PMF): eight with normal karyotype and seven with PMF-characteristic cytogenetic abnormalities, including der(6)t(1;6)(q21-23;p21.3) (n = 4), der(7)t(1;7)(q10;p10) (n = 2), del(20)(q11.2q13.3) (n = 3), and complex karyotype (n = 1). We describe seven novel deletions/translocations in five patients (including two with normal karyotype) whose breakpoints were PCR-validated and involved MACROD2, CACNA2D4, TET2, SGMS2, LRBA, SH3D19, INTS3, FOP (CHTOP), SCLT1, and PHF17. Deletions with breakpoints involving MACROD2 (lysine deacetylase; 20p12.1) were recurrent and found in two of the 15 study patients. A novel fusion transcript was found in one of the study patients (INTS3-CHTOP), and also in an additional non-study patient with PMF. In two patients with der(6)t(1;6)(q21-23;p21.3), we were able to map the precise translocation breakpoints, which involved KCNN3 and GUSBP2 in one case and HYDIN2 in another. This study demonstrates the utility of HRMPS in uncovering submicroscopic deletions/translocations/fusions, and precise mapping of breakpoints in those with overt cytogenetic abnormalities. The overall results confirm the genetic heterogeneity of PMF, given the low frequency of recurrent specific abnormalities, identified by this screening strategy. Currently, we are pursuing the pathogenetic relevance of some of the aforementioned findings.
Skin Conditions in Children
Authors: R. P. Warin
Journal: BMJ (1965)

SIR,-In 1947 we published a paper' entitled " Studies on the Mechanism of the Fanconi Syndrome."The subject of the study was a man aged 34, presenting in 1945 with gross osteomalacia.He was found to have the full renal-tubular abnormalities usually associated with the name " Fanconi syndrome "-namely, renal tubular reabsorp- tive defects of phosphate, glucose, and amino- acid, with renal-tubular acidosis.He was also found to have severe cirrhosis, from which he died in early 1946, his bone disease having been largely controlled by treatment.We thought then that cirrhosis was an occasional association of " Fanconi syndrome," indeed we then speculated that the cirrhosis might have resulted from amino-acid depletion in consequence of the amino-aciduria.'(We do not believe this any longer.)Our subsequent clinical studies at Univer- sity College Hospital have shown that cirrhosis is only consistently associated with a childhood form of the Fanconi syndrome, as in the case described by Baber.3One of us (C.E. D.) began to get worried about the original case in an adult man, since no further similar " idiopathic " cases have since been seen or heard of in this age group.The postmortem material was no longer available, but a measured aliquot of the patient's 24-hour urine of 7 January 1946 has been traced in our cold room.It has been sent to Professor J. N. Cumings, who reports that it contained 45 jeg./100 ml. of copper, or 594 pig. in the 24-hour specimen.He adds that this grossly excessive excretion is "undoubtedly diag- nostic of Wilson's disease if it cannot be explained by contamination."It would seem necessary to record now that the diagnosis of " idiopathic adult Fanconi syndrome with cirrhosis of the liver" prob- ably no longer exists on the basis of present evidence.Any apparent case should there- fore be carefully screened for causes of secondary renal tubular or of liver dysfunction such as myeloma, and heavy-metal poisoning-but especially for Wilson's dis- ease, for which we now have excellent treatment.4The existence of adult Fanconi syndrome without cirrhosis remains fully substantiated.-We are, etc.,
WHERE IS THE FUNDUS OF THE BLADDER?
Authors: BRANSFORD LEWIS
Journal: JAMA (1913)

Some years ago my attention was attracted to what appeared to me a curious eccentricity of nomenclature in vesical anatomy, namely, that of applying to the top of the bladder the term "fundus"; a word evidently allied to and having a common origin with such words as "foundation," "fundament" or base. It seemed unreasonable and illogical, and yet the evidence that it was correct appeared on all hands; in all current writings such usage was in vogue. On the other hand, the term "fundus of the uterus," in which the base was pointed upward, seemed unquestioned as to its authenticity and anatomic regularity. So for a time my doubts were quieted; but gradually my Missouri instinct prevailed and I sought headquarters for information on the subject. Every book on anatomy that I consulted not only failed to give sanction to such usage, but also applied the term "fundus," as do
RATIONAL TREATMENT OF PERTUSSIS.
Authors: FRANCIS T. B. FEST
Journal: JAMA (1895)

With every disease its etiology shows us the way for its treatment. Therefore it is necessary to recapitulate the etiology of every disease for which we wish to outline the therapeutics. Pertussis or whooping cough is a contagious disease, which manifests itself in spasmodic cough. Although some bacteriologists have found in the sputum, bacilli, we are unable so far to determine their rôle, whether causing, accompanying or only accidental. It is a local disease of the larynx, acting upon the nerve supply, and causing spasms of this organ. The course of the disease shows three distinct phases: the catarrhal, paroxysmal and declining. The first stage shows only symptoms of mild catarrh of the bronchi, nose or conjunctiva. Pathognostic for pertussis is only the excessive watery secretion from the affected regions. This phase lasts from two to seven weeks, with infants often a few days only. The paroxysmal stage affirms the
Measurement of bronchial reactivity: a question of interpretation.
Authors: J Orehek
Journal: Thorax (1982)

Measurement of bronchial reactivity: a question of interpretation Sir,-In their letter in the December 1981 issue (p 960) Dr EH Walters and his colleagues indicate that asthmatics with abnormal baseline values of specific airway conduc- tance (sGaw) showed a lower reactivity to histamine (slope of dose-response curve) than normal subjects.They sug- gest that we reached an opposite conclusion' because we inappropriately used an arithmetic plot of the doses.The rules of in vitro pharmacology, however, do not necessarily apply to in vivo pharmacology.In vitro pharmacologists use a log plot of doses for two purposes: (1) linearising the dose-response curve around the response representing 50% of the maximal response; (2) determining the relative potency of various agonists yielding parallel dose-response lines.2In vitro, the sigmoid shape of the dose-response curves obtained with a log plot is justified by the theory of drug-receptor interaction.In vivo, factors other than drug-receptor interaction intervene to determine the shape of the dose-response curve and a sigmoid shape is unlikely to occur.3Furthermore, a maximal response cannot be obtained.In our study' the dose-response relationships obtained