tbuckley/cabot-search huggingface dataset:
Medicine in Politics
Authors: A. W. Macara
Journal: BMJ (1969)

<h3>Abstract</h3> In most species, elaborate programs exist to protect chromatin and maintain its integrity over cell cycles and generations. However some species systematically undergo excision and elimination of portions of their genome in somatic cells in a process called programmed-DNA elimination (PDE). PDE involves the elimination of mainly repeated elements but also protein-coding genes. PDE has been described in approximately 100 species from very distinct phyla, and more extensively in the parasitic nematodes <i>Ascaris</i> and in the unicellular Ciliates. In Ciliates, where PDE is pervasive, the underlying mechanisms have been studied and involve small RNA-guided heterochromatinization. In striking contrast, chromatin recognition and excision mechanisms remain mysterious in Metazoans, because the study species are not amenable to functional approaches. Above all, the function of such a mechanism, which has emerged repeatedly throughout evolution, is unknown. Answering these questions will provide significant insights into our understanding of chromatin regulation and genome stability. We fortuitously discovered the phenomenon of PDE in all species of the free-living nematode genus <i>Mesorhabditis. Mesorhabditis</i>, which belong to the same family as <i>C. elegans</i>, have a small ∼150 Mb genome and offer many experimental advantages to start elucidating the elimination mechanisms in Metazoans. In this first study, we have used a combination of cytological observation and genomic approaches to describe PDE in <i>Mesorhabditis</i>. We found that the dynamics of chromosome fragmentation and loss are very similar to those described in <i>Ascaris</i>. Elimination occurs once in development, at the third embryonic cell division in all 5 presomatic blastomeres. Similar to other species, <i>Mesorhabditis</i> eliminate repeated elements but also about a hundred unique sequences. Most of the eliminated unique sequences are either pseudogenes or poorly conserved protein-coding genes. Our results raise the possibility that PDE has not been selected for a gene regulatory function in <i>Mesorhabditis</i> but rather mainly is a mechanism to irreversibly silence repeated elements in the soma.
Bone Lesion in a Child
Authors: Murray L. Janower
Journal: JAMA (1964)

<h3>Dr. Donald L. Stone:</h3> These are the roentgenograms (Fig 1) of a 12-year-old female who was in good health until one day prior to admission when she fell down some stairs in her home. After falling, she noted the onset of a dull ache in the right lower thigh. She continued to have pain in this region, particularly on motion. Twenty-four hours later, she appeared at the emergency room. Her past history, review of systems, and family history were not contributory. The physical examination was essentially negative except for the presence of moderate tenderness over the distal right femur. One observer noted an increased warmth in this area. Laboratory examination revealed a white blood cell count of 12,200/cu mm with 73% polymorphonuclear cells and 19% lymphocytes; a hemoglobin of 14.2 gm/100 cc and a negative urine. The calcium was 9.8 mg/100 cc, phosphorus 3.7 mg/100 cc, and alkaline phosphatase 8.4
PTU-093 Inappropriate inflammatory responses in the ileum of ulcerative colitis patients
Authors: J Landy, H O Al-Hassi, S T Peake, N English, P J Ciclitira, R J Nicholls, S K Clark, S C Knight, A L Hart
Journal: Gut (2012)

<h3>Introduction</h3> Inflammation in ulcerative colitis (UC) is restricted to the colon. However, up to 50% of UC patients develop inflammation of the small bowel following restorative proctocolectomy (RPC). We hypothesised that in UC patients, ileal lamina propria dendritic cells would have a more “stimulatory” phenotype than in normal controls predisposing UC patients to pouch inflammation following RPC. <h3>Methods</h3> Mucosal biopsy samples were taken from the ileum of UC patients undergoing RPC and from healthy controls undergoing colonoscopy. Lamina propria dendritic cells were isolated from biopsy tissue by collagenase digestion. DCs were identified as an HLA DR+, lineage- (CD3-, CD14-, CD16-, CD19-, CD34-, CD56-) population and expression of Toll-like receptors (TLRs), homing markers and co-stimulatory markers were measured by multicolour flow cytometry. T-tests were performed for statistical analysis. <h3>Results</h3> There were no differences between the percentage of dendritic cells expressing TLR 2 (30.5±11.5% vs 32.5±8.8%) or TLR 4 (38.6±5.8% vs 38.8±7.2%) in the UC and healthy control ileum. A significantly greater percentage of lamina propria dendritic cells expressed the gut homing marker β7 in the normal ileum (33.8±9.6%) compared with the UC ileum (6.4±3.2%, p=0.007) as well as the co-stimulatory marker CD40 (80±2.9% vs 48.6±5.7%, p=0.001). <h3>Conclusion</h3> Contrary to our expectations, lamina propria dendritic cells in the ileum of UC patients appear to have a less “stimulatory” phenotype than in normal controls. There may therefore be an absence of appropriate effector responses and reduced regulation by T-cells in the UC ileum. Further work is necessary to assess the T-cell responses to dendritic cell stimulation in the ileum of UC and in healthy controls. <h3>Competing interests</h3> None declared.
EXPERIMENTS IN MALNUTRITION
Authors: V. H. Mottram
Journal: BMJ (1928)

6XDICALIoWWIntracranial T un o-ur.To explain how relief cal -be obtained by means of hvper- tcnic solutions in cases -of iintracranijal tumour it is iece8- sary to give a brief account of the way in whichl a r'ise of intr acranial pressure is brought about in this condition.We may recognize three factor s whiclh contribute to this result-the direct pressure of the tumour, the effect of the tum-nour upon the initracranial circulation, and the com- biniation of both of these factors to produce internial hydro- cephalus.It is easy to understand that the growth of a tumrkour' within thle brain raises the intracranial pressure in its immediate neighbourhood.In additioii, by pressure upon surrouniding veins, it raises the venous pressure locally, Rnd in many cases throughout the whlole cranial cavity.The local venous congestion leads to oe-dema of ar eas of brain surroundinlg tho tumiour', aind so intensifies thle local rise of pressure.The main causes of internal hydrocephalus in cases of intracranial tumour are obstruction to the free passage of fluid froom the ventricles by the tumour, and the general rise of intracr-anial venous pres- sure, which leads to both increased formation and impaired absorption of cerebro-spinal fluid.Thus anl intracranial tumoul sets up a series of vicious circles whereby the iijtracranial pressure, once raised, tends to rise more and more.The value of hypertonic solutions in cases of cerebral tu-mour lies in the fact that they break these vicious circles and l)ermit a readjustment of the volumes of the intra- ci aniial conitents wlhich miiay last for a considerable time.This they do miiainly bv reducinig the formation anid iniereas- inig tlle absorption of cerebro-spiiial fluid, anid so tempor- arily relieving the hydrocephalus.The following are the chiief indications for emnploying them.
SPAIN AS THE CRADLE OF PSYCHIATRY
Authors: PETER BASSOE
Journal: American Journal of Psychiatry (1945)

Was Spain a "cradle of psychiatry"? She certainly was not the mother of psychiatry for that honor belongs to Greece. In the middle ages she stressed charity in her Christianity, and for some centuries both the Christians and Mohammedans showed remarkable tolerance. The Moors gave to Jews as much freedom as to Christians. Some of the churches were used by Mohammedans on Friday, Jews on Saturday, and Christians on Sunday. On account of the relative isolation from the rest of Europe Greek and Roman traditions were maintained and strongly reenforced by the same traditions brought by the Arabs, and still more by the oncoming renaissance. Spain was relatively prosperous and powerful as well, and all these factors helped to bring about the remarkable attention given to the insane in the fifteenth and sixteenth centuries. Spain truly was the cradle of psychiatry but she later neglected the infant, and in the following centuries she actually fell behind other countries. With the advent of the inquisition and the hunt for heretics charity was largely lost sight of, and, as usual, the insane were the first to be neglected. During the bitter warfare between Christians and Moors, the latter also became fanatic and more intolerant. On account of the intellectual isolation of Spain, on which all historians agree, it is not likely that the "cradling" of psychiatry in Spain did much to further better care of the insane in the rest of Europe. It was probably known to very few until Pinel visited Spain at the time of Napoleon.
An Introduction to Dermatology
Authors: Norman Walker
Journal: JAMA (1934)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats.
Authors: M Ruzicka, B Yuan, F H Leenen
Journal: Circulation (1994)

BACKGROUND The role of nonhemodynamic cardiac trophic mechanisms differs not only between different models of cardiac hypertrophy but also within the same model for development versus maintenance of cardiac hypertrophy. Our previous studies pointed to a major role for the renin-angiotensin system (RAS) as a cardiac trophic stimulus in the remodeling of the heart in response to volume overload by aortocaval shunt or minoxidil treatment. METHODS AND RESULTS In the present study, we evaluated the effects of blockade of the RAS by the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan on left ventricular (LV) and right ventricular mass and LV dilation in relation to changes in central hemodynamics during the maintenance of minoxidil and aortocaval shunt-induced cardiac hypertrophy. Both blockers similarly decreased LV end-diastolic pressure (LVEDP) and LV peak systolic pressure, whereas cardiac output remained unchanged in both models of volume overload. This suggests a major contribution of improved LV performance and decreased afterload to the decrease in cardiac preload by the two blockers rather than decreased venous return. Both blockers reversed LV hypertrophy in parallel to their effects on LVEDP in both models of volume overload. In minoxidil-treated rats, the extent of reversal in LV mass and dilation by the two blockers was similar to "spontaneous regression" after discontinuation of minoxidil treatment. CONCLUSIONS These results indicate that in contrast to the development phase of cardiac hypertrophy, the RAS does not contribute to the maintenance of volume overload-induced cardiac hypertrophy in these two models via direct cardiac trophic effects. The RAS, however, maintains cardiac hypertrophy indirectly by contributing to the persistence of high filling pressures.
Current Strains for Mental Health Trainees
Authors: C. BROOKS BRENNEIS, DORI LAUB
Journal: American Journal of Psychiatry (1973)

Mental health trainees are currently troubled by conflicts between the "new" radical psychiatry and "old" professionalism. The conflict has been shaded with social and political overtones such that trainees view their worth as professionals not in terms of their skill, but rather in terms of how involved they are in the social and political arena. The authors feel that as a result, trainees have difficulty accepting their fallibility, tend to attribute psychiatric illness to social ills, and deal with their doubts about their therapeutic efficacy by committing themselves to action rather than to reflection.
Infant of the Addicted Mother
Authors: Carl Zelson
Journal: New England Journal of Medicine (1973)

HEROIN addiction and now also methadone addiction among pregnant women have been increasing steadily over the years. The full scope of the problem is unknown because of the illicit nature of the drug traffic. However, with the increasing incidence of drug addiction in general, and since 85 per cent of the women involved are in the childbearing age (15 to 40 years), one would thus also expect an increase in the number of births of infants of drug-addicted mothers.It has been estimated that there are between 400,000 and 600,000 heroin addicts in the United States. The latter figure is . . .
Baseline plasma fibrinolysis and its correlation with clinical manifestations in patients with Raynaud's phenomenon.
Authors: C S Lau, M McLaren, I Mackay, J J Belch
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--(1) To assess if patients with various forms of Raynaud9s phenomenon (RP) have abnormal plasma fibrinolysis that may contribute to diminished digital blood flow; (2) to assess whether patients with RP with evidence of endothelial damage have abnormal plasma fibrinolysis; (3) to determine the clinical relevance of abnormalities, if any, in plasma fibrinolysis in patients with RP. METHODS--One hundred and sixty eight patients with significant RP were studied--46 had primary Raynaud9s disease (RD), 32 had suspected Raynaud9s syndrome secondary to an undifferentiated connective tissue disorder (undifferentiated CTD), 25 had Raynaud9s syndrome associated with atherosclerosis (athero RS), and 65 had an underlying connective tissue disease (CTD RS). All attended in the morning after a low fat light breakfast. After a clinical history was obtained, venous blood samples were collected without stasis for assays of plasma fibrinolysis and factor VIII von Willebrand factor antigen (fVIII vWF Ag). Results were compared with those obtained from normal subjects matched for sex and age. As patients with athero RS were significantly older than the other patients with Raynaud9s phenomenon, two groups of control subjects were recruited--namely, 9old9 and 9young9 control subjects. RESULTS--Patients with CTD RS and athero RS had higher concentrations of fVIII vWF Ag (CTD RS median 174.5 range (45-370)% v 100 (38-202)%, p &lt; 0.001; athero RS 182-5 (100-240)% v 100 (50-158)%, p &lt; 0.001). Both had raised fibrinogen (CTD RS 3.25 (1.9-6.8) g/l v 2.4 (1.2-4.2) g/l, p &lt; 0.001; athero RS 3.4 (2.2-6.2) g/l v 2.5 (1.8-3.9) g/l, p &lt; 0.001) and both had diminished fibrinolysis with reduced plasminogen activator activity (CTD RS 79.5 (31-72) mm2 v 92 (37-197) mm2, p &lt; 0.04; athero RS 73 (45-125) mm2 v 98 (41-197) mm2, p &lt; 0.03). Patients with CTD RS also had raised plasminogen activity (3.3 (2.3-5.8) cU/ml v 2.9 (1.5-5.4) cU/ml, p &lt; 0.001). On the contrary, patients with primary RD and undifferentiated CTD had normal fibrinogen and plasma fibrinolysis. Within each patient group, no significant differences in any of the measured variables were found between those who had RP all year and those who had RP in the winter only, those with RP of the hands only and of hands and feet, or those with and without digital ulcers. CONCLUSION--Diminished plasma fibrinolysis is found in patients likely to have endothelial damage (CTD RS and athero RS). These changes are probably a consequence rather than a cause of the disease.
Sylvia Dische (nee Goldberg)
Authors: F. Dische
Journal: BMJ (2008)

Sylvia came to Britain from South Africa in 1950 to further her training as a paediatrician, and never went back. After studies in Edinburgh, she held junior posts at the Canadian Red Cross Memorial Hospital, Taplow, and in London. Following marriage in 1953, she worked part-time in schools and clinics in …
Abstract LB-233: Unique physicochemical properties of the potent FGFR 1, 2, 3 and 4 inhibitor JNJ-42756493 contribute to prolonged target shutdown
Authors: Eleonora Jovcheva, Caroline Paulussen, Patrick Van Bergen, Yolanda Chong, Jorge Vialard, Laurence Mevellec, Patrick Angibaud, Timothy Perera
Journal: Cancer Research (2014)

Abstract The ability of drugs to penetrate into cells and tissues is a fundamentally important property that is essential for the efficacy of drugs targeting intracellular processes. Many weakly basic small molecule drugs are known to accumulate extensively in acidic sub-cellular compartments such as lysosomes, through a process called ion trapping that is dependent on the physico-chemical properties of a compound. ‘Lysosomal uptake’ has been shown to significantly influence the activity of many agents, including anticancer drugs, both positively and negatively. Here we describe the unique physico-chemical properties of JNJ-42756493, a potent inhibitor of fibroblast growth factor receptors (FGFRs) 1, 2, 3 and 4, currently undergoing clinical testing for the treatment of malignancies with FGFR pathway activating alterations. JNJ-42756493 has weakly basic and lipophilic characteristics, is highly permeable, and is fluorescent when exposed to UV light. The fluorescent property of JNJ-42756493 enabled rapid and convenient visualization of the drug (spatial and temporal localization) within the lysosomes of cultured cells exposed to JNJ-42756493. In order to evaluate the influence of this lysosomotropic property on the activity of JNJ-42756493, FGFR phosphorylation was monitored in a series of wash-out experiments performed in various cellular models with FGFR1 or FGFR2 amplifications. This comparative washout analysis demonstrated prolonged FGFR kinase inhibition by JNJ-42756493 in comparison to other FGFR inhibitors lacking lysosomotropic properties. This qualitative fluorescence-based data was complemented by accurate quantification of the amount of compound taken up by the cells through the use of radiolabelled JNJ-42756493. Our results unequivocally demonstrate that JNJ-42756493 accumulates at high concentrations within the lysosomal compartment of cells without undergoing metabolism. The continued, long lasting effects on the target FGF receptor kinase inhibition following drug washout, suggest a novel intrinsic slow release of the unmodified drug from these intracellular stores. The lysosomotropic property of JNJ-42756493 is proposed to be a major contributor to the efficient and persistent inhibition of FGFR phosphorylation leading to potent cellular and in vivo activity. Citation Format: Eleonora Jovcheva, Caroline Paulussen, Patrick Van Bergen, Yolanda Chong, Jorge Vialard, Laurence Mevellec, Patrick Angibaud, Timothy Perera. Unique physicochemical properties of the potent FGFR 1, 2, 3 and 4 inhibitor JNJ-42756493 contribute to prolonged target shutdown. [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-233. doi:10.1158/1538-7445.AM2014-LB-233
Consequences of Queuing for Care at a Public Hospital Emergency Department
Authors: Andrew B. Bindman
Journal: JAMA (1991)

To determine whether the length of a queue at a public hospital emergency department was associated with increased likelihood of patients' leaving without being seen by a physician and whether leaving adversely affected patients' health or affected their subsequent use of health care services.Observational cohort. Patients were surveyed during 1 week in July 1990 and received a follow-up survey 7 to 14 days later. The responses of patients who left without being seen by a physician were compared with those who were seen by a physician.Emergency department at San Francisco (Calif) General Hospital.All English-, Spanish-, and Cantonese-speaking adults waiting for emergency care were eligible. Of 882 eligible individuals, 700 agreed to participate; 85% of enrolled subjects saw a physician and 15% left without being seen. Demographic characteristics of patients who were and who were not seen were not significantly different.Emergency department waiting time and changes in patients' self-reported health.Patients were more likely to leave as waiting times increased. At follow-up, patients who left without being seen were twice as likely as those who were seen to report that their pain or the seriousness of their problem was worse. Only 4% of patients who left required subsequent hospitalization, but 27% returned to an emergency department.Many patients can appropriately decide whether their problem is truly urgent and make alternative plans in the face of long waits, but the health of some patients may be jeopardized by long queues for emergency care.
THE HEMIC BASOPHIL
Authors: George S. Graham
Journal: The Journal of Experimental Medicine (1920)

1. The basophilic granule of blood and marrow cells does not show the brown color reaction with benzidine solutions that is characteristic of the neutrophilic and eosinophilic granules. It differs from these types also in other important microchemical and physical particulars. 2. The hemic basophil which bears these granules is peculiar from a purely cytological standpoint, while physiologically it appears to be devoid of any functional activity comparable with that of the other granulocytes. 3. The peculiarities exhibited seem in every instance, at least for mammalian blood, best explained as evidence that the basophil is a degenerated or degenerating cell. It is probably derived from the eosinophilic cells and perhaps in rare cases from those of neutrophilic type.
The world is watching the English experiment
Authors: F. Godlee
Journal: BMJ (2008)

It may seem parochial for the BMJ to use so much space discussing the NHS—and the English NHS at that. But I make no apologies—firstly, because if doctors are to take the lead in health care, as they must and as they are being encouraged to do, they need to understand the systems that deliver it. Secondly, because the wider world is watching what may come to be known as the English experiment. As evidence of this, the New England Journal of Medicine has published another paper on England’s use of quality indicators and performance payments. As Alison Tonks describes it (doi: 10.1136/bmj.a891), the …
PERIODIC MEDICAL EXAMINATIONS OF APPARENTLY HEALTHY PERSONS
Authors: HAVEN EMERSON
Journal: JAMA (1923)

From both medical and lay sources requests have come to the American Medical Association to prepare a description of the objects to be attained, the methods to be employed and results which may be expected from inquiry into and observation of the tissues and physiologic functions of persons, young and old, who are not at the time aware of any disease or defect which is causing them to seek medical relief. By resolution of the House of Delegates in June, 1922, the Council on Health and Public Instruction was authorized to prepare forms suitable for use by practitioners of medicine in carrying out the purposes of the periodic health examination, and the statement here submitted is offered in fulfilment of this obligation.<sup>1</sup> The preparation of forms for record of the applicant's history and the medical examination, without explanatory text as to the intent and meaning of the questions and