tbuckley/cabot-search huggingface dataset:
Making access to health care more equal: the role of general medical services.
Authors: G Bevan, J Charlton
Journal: BMJ (1987)

The Resource Allocation Working Party (RAWP) recognised the need to consider both health authority and primary care services in achieving its objective. RAWP and the subsequent Advisory Group on Resource Allocation (AGRA) found (but did not publish) considerable variation in resources used by both services but could not find a clear relation between them. Statistics provided by the DHSS were used to compare spending by 80 area health authorities in 1980-1 with expenditure per head on general medical services by their corresponding family practitioner committees. There was considerable variation in the provision of resources for both services and no clear relation between the variations in spending on each service. Only 40 of the 80 areas had both health authority and family practitioner committee spending levels within 10% of "target." Subregional inequalities in resources tend to be related to variations in admission rates, which in turn are related to general practitioners' referral behaviour. These results emphasise the importance of finding out more about inequalities in the provision of general medical services and their relation to the use of hospital services. They also suggest that RAWP's aim of equality of opportunity of access to health care resources may be achieved only if general medical services are brought into the equation as well.
CENTRAL VENOUS PRESSURE IN RELATION TO CARDIAC “COMPETENCE,” BLOOD VOLUME AND EXERCISE
Authors: E. M. Landis, E. Brown, M. Fauteux, C. Wise
Journal: Journal of Clinical Investigation (1946)

The mechanism by which venous pressure is elevated in human heart disease, and the exact relation between venous pressure and the plethora of late cardiac failure are still uncertain.Starling, primarily from his results with the heart-lung preparation (1), suggested the following se- quence:Cardiac failure --elevated venous pressure -> accumulation of blood in the large veins -- compensatory arteriolar constriction -> anoxia of bone.marrow --increase in blood volume.This hypothesis with its tacit assumption that "back pressure" occurs in the intact animal, as it does more clearly in the heart-lung preparation, has been challenged recently by Starr, Jeffers and Meade (2), and by Warren and Stead (3) who relate venous pressure to cardiac failure essentially as follows:"Impaired cardiac function" -> decreased renal excretion of sodium and water (mechanism un- known) -4 increased blood volume -> elevated venous pressure.Starr et al, (2) observed that acute damage of the right ventricle failed to elevate significantly the venous pressures of dogs, but these studies were limited to the resting state.Warren and Stead (3) found in cardiac patients, also during rest, that administering water and sodium chlor- ide increased blood volume before venous pressure rose significantly.They concluded that the earl- iest manifestation of cardiac insufficiency is a re- tention of fluid, the cause of which is not clear, associated with an increase of blood volume.This plethora or hypervolemia is said then to be re- sponsible for the elevated venous pressure which 'Research Fellow in Physiology, Commonwealth Fund.
Is False Membrane Essential to Diphtherite?
Authors: F. Needham
Journal: BMJ (1858)

MEDICAL NEWS.(MARCa 20, 185I the exhibition of steel, it seemed to produce some beneficial efects In rheumatism, he had very rarely seen any good done by galvanism.The cases said to be relieved by this agent ought to be classified; and the mode of applying the instruments should be most distinctly indicated.Mr. BALLARD wished to know if the auithor bad seen any mineral (lead or mercury) deposited from the body in the electric bath.Certain advertisements pronounced that such effects were obtained.
Late-Onset Manifestation of Antenatal Bartter Syndrome as a Result of Residual Function of the Mutated Renal Na+-K+-2Cl− Co-Transporter
Authors: Carsten A. Pressler, Jolanta Heinzinger, Nikola Jeck, Petra Waldegger, Ulla Pechmann, Stephan Reinalter, Martin Konrad, Rolf Beetz, Hannsjo[Combining Diaeresis]rg W. Seyberth, Siegfried Waldegger
Journal: Journal of the American Society of Nephrology (2006)

Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co-transporter result in severe, prenatal-onset renal salt wasting accompanied by polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are described two brothers who presented with hyperuricemia, mild metabolic alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption along the thick ascending limb of Henle's loop was deduced from a reduced increase in diuresis and urinary chloride excretion upon application of furosemide. Molecular genetic analysis revealed that the brothers were compound heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co-transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux assays after heterologous expression in Xenopus oocytes revealed significant residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to no activity of the NKCC2-D918fs frameshift mutant construct. However, coexpression of the two mutants was not significantly different from that of NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined by luminometric surface quantification was not significantly different from wild-type protein, pointing to an intrinsic partial transport defect caused by the p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and for the first time establishes a mild phenotype-associated SLC12A1 gene mutation.
Gangrene After Inadvertent Intraarterial Injection of Amphetamine: Appearance on a Three-Phase Tc-99m MDP Bone Scan
Authors: Vito Rubino, Ian D. Kirkwood, Max Bellon, Barry E. Chatterton
Journal: Clinical Nuclear Medicine (2006)

A 39-year-old man presented to the emergency department with an ischemic left hand after inadvertent injection of amphetamine into the left radial artery 4 days before presentation. Examination revealed a gangrenous left thumb and index finger without clear demarcation and a weak radial pulse. Brachial angiography demonstrated absent blood flow to the digital arteries of the distal left thumb and entire left index finger. A 3-phase Tc-99m MDP (methylene diphosphonate) bone scan was performed 6 days later, which demonstrated nonviability of the distal phalanx of the left thumb and left index finger, distal to the midportion of the proximal phalange. The patient subsequently underwent amputation of the left thumb and index finger at these levels with the bone scan accurately reflecting the operative findings. The 3-phase bone scan was useful in determining the need for and extent of amputation in this case.
RASAL2 activates RAC1 to promote triple-negative breast cancer progression
Authors: Min Feng, Yi Bao, Zhimei Li, Juntao Li, Min Gong, Stella Lam, Jinhua Wang, Diego M. Marzese, Nicholas Donovan, Ern Yu Tan, Dave S.B. Hoon, Qiang Yu
Journal: Journal of Clinical Investigation (2014)

Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for recurrence in these individuals remains poorly understood. Here, we demonstrate that RASAL2, which encodes a RAS-GTPase–activating protein (RAS-GAP), is a functional target of anti-invasive microRNA-203 and is overexpressed in a subset of triple-negative or estrogen receptor–negative (ER-negative) breast tumors. As opposed to luminal B ER-positive breast cancers, in which RASAL2 has been shown to act as a RAS-GAP tumor suppressor, we found that RASAL2 is oncogenic in TNBC and drives mesenchymal invasion and metastasis. Moreover, high RASAL2 expression was predictive of poor disease outcomes in patients with TNBC. RASAL2 acted independently of its RAS-GAP catalytic activity in TNBC; however, RASAL2 promoted small GTPase RAC1 signaling, which promotes mesenchymal invasion, through binding and antagonizing the RAC1-GAP protein ARHGAP24. Together, these results indicate that activation of a RASAL2/ARHGAP24/RAC1 module contributes to TNBC tumorigenesis and identify a context-dependent role of RASAL2 in breast cancer.
Cholesterol cholelithiasis in the prairie dog: Role of mucin and nonmucin glycoproteins
Authors: Nezam H. Afdhal, Dahai Gong, Niu Niu, Bradley Turner, Thomas J. Lamont, Gwynneth D. Offner
Journal: Hepatology (1993)

The aims of this study were to examine the effect of exogenous prostaglandin on mucin secretion and to determine the role of nonmucin glycoproteins on gallstone formation in the prairie dog model of cholesterol cholelithiasis. The concentration of total glycoprotein and nonmucin glycoproteins was measured in gallbladder bile from four groups of prairie dogs fed a control diet or a diet supplemented with 1.2% cholesterol with or without simultaneous subcutaneous administration of prostaglandin E 1 . Cholesterol feeding resulted in an increased concentration of concanavalin-A binding-proteins in gallbladder bile associated with an increase in pronucleating activity in vitro . Treatment with prostaglandin E 1 and cholesterol feeding was associated with a significant increase in the incidence of cholesterol gallstone formation. Prostaglandin E 1 treatment in the cholesterol-fed animals increased biliary concentrations of total glycoprotein and concanavalin-A-binding glycoproteins. Therefore the increased biliary glycoprotein level in cholesterolfed, prostaglandin E 1 -treated prairie dogs, which reflects higher levels of mucin and nonmucin glycoproteins, appears to be an important factor in gallstone formation. (Hepatology 1993;17:693-700.)
Promoting walking and cycling as an alternative to using cars: Vested interests doom puny healthcare interventions
Authors: Douglas J Carnall
Journal: BMJ (2004)

EDITOR—Ogilvy et al's systematic review on promoting walking and cycling as an alternative to using cars treats motoring as if it were a disease that can be cured, without examining the social forces that lead to car use.1 The effects they find in their review are hardly surprising, given the social currents opposing …
AORTIC STENOSIS MANIFESTED AS CHRONIC COR PULMONALE
Authors: Louis A. Soloff
Journal: JAMA (1952)

Aortic stenosis is notoriously difficult to diagnose during life in the absence of classical findings. Characteristically, a harsh systolic murmur is audible in the second interspace to the right of the sternum, in which a systolic thrill is palpable.<sup>1</sup>The murmur is transmitted upward into the vessels of the neck. The second aortic sound is faint or absent. The blood pressure is low, and the heart rate is slow. The radial pulse rate is low and slow in rising. Classical findings are frequently absent. There may be associated hypertension that changes the character of the pulse and of the second aortic sound; this can also occur with the accentuated second pulmonic sound present in failure of the left side of the heart or in mitral stenosis. The murmur may not be intense enough either to give rise to a thrill or to be transmitted upward. On the other hand,
A Note on Statistical Usage
Authors: Norman G. Hawkins
Journal: JAMA (1961)

SEVERAL WRITERS have deplored recently the lack of technical preparation behind much of contemporary clinical research.<sup>1-3</sup>On the other hand, the difficulty often seems to be that of the same general nature which may divide a staff conference or a society meeting. It is not so much the marshalling of evidence as it is the use of common sense in interpretation. This point may be illustrated by the controversy over BCG vaccination. There seems to be nothing wrong with the statistical analysis on either side of the question, but statistics are of much less importance than the conclusions which may be drawn legitimately with reference to the same figures. Technical skill in compiling the evidence may help evolve a decision, but the decision is made by the rules of common sense. There are also rules of common sense inherent in statistical methods, rules derived either from the mathematical theory
PSYCHIC AND EMOTIONAL FACTORS IN THEIR RELATION TO DISORDERS OF THE DIGESTIVE TRACT
Authors: JAMES S. McLESTER
Journal: JAMA (1927)

Since a symposium is intended to develop individual opinions taken from diverse points of view, I shall express my own concept of the causes underlying the digestive disorders of a certain group of mildly psychoneurotic patients. This group embraces those emotionally unbalanced people who, because of digestive distress, real or imaginary, commonly consult the internist; it does not include those who, because of an obvious psychoneurosis, properly seek the advice of a psychiatrist. A relatively large number of the patients who find their way to the consultant are so-called neurasthenics; otherwise, most of them would in all likelihood have been relieved by the first physician whose advice they sought. Of 5,700 patients seen in my office during the period of our present method of work, the records of the last thousand have been reviewed with the object of determining the etiologic rôle played by emotional and psychic influences. Of these
Gene variation in IL10 and susceptibility to chronic hepatitis B
Authors: Tian-Chen Zhang, Wen-Feng Zhang, Yu-Qin Zhao, Fa-Ming Pan, Yu-Feng Gao, Hui Yuan, Xiao-Qing Liu, Xiao-Dan Chen, Cai-Wen Zeng, Li-Juan Liu, Yue-Qing Chen
Journal: Journal of Infection (2014)
Variant <i>TREM2</i> as Risk Factor for Alzheimer's Disease
Authors: Harald Neumann, Mark J. Daly
Journal: New England Journal of Medicine (2012)

Current knowledge about the pathogenic mechanism of Alzheimer's disease is based mainly on rare, high-penetrance variants in genes encoding amyloid precursor protein, presenilin 1, and presenilin 2, which result in familial early-onset Alzheimer's disease. However, Alzheimer's disease is predominantly a sporadic late-onset disease with exponentially increasing prevalence starting at the age of 65 years. Genomewide association studies have recently identified several risk variants for late-onset Alzheimer's disease, but aside from the well-known ε4 allele of apolipoprotein E, these variants are generally associated with very low risk; in addition, such variants are noncoding and more challenging to link to molecular function. . . .
The Drunk in Court: Survey of Drunkenness Offenders from Two London Courts
Authors: D. Gath, C. Hensman, A. Hawker, M. Kelly, G. Edwards
Journal: BMJ (1968)

A total of 151 men charged with drunkenness with or without aggravations were interviewed immediately after their appearance before the magistrates. The survey was conducted in two Metropolitan courts; one in an area frequented by vagrants, and the other in a mixed middle-class and working-class area.Few of the offenders were casual roisterers and the majority had a serious drinking problem. Half the offenders showed evidence of chemical dependence on alcohol as determined by morning shakes, morning relief drinking, amnesias, inability to stop drinking, and hallucinatory experiences.The majority of the offenders were suffering from gross social isolation.Existing ways of dealing with such men seem inadequate. A rehabitation service is needed, with hostel accommodation, and particular attention should be paid to first offenders.
Solid cancers after allogeneic hematopoietic cell transplantation
Authors: J. Douglas Rizzo, Rochelle E. Curtis, Gérard Socié, Kathleen A. Sobocinski, Ethel Gilbert, Ola Landgren, Lois B. Travis, William D. Travis, Mary E. D. Flowers, Debra L. Friedman, Mary M. Horowitz, John R. Wingard, H. Joachim Deeg
Journal: Blood (2008)
Omeprazole and aryl hydrocarbon hydroxylases: Should we be worried?
Authors: J. C. Kolars, D. K. Turgeon, P. B. Watkins
Journal: Hepatology (1991)

Diaz and colleagues have carefully studied the effects of omeprazole on the expression of cytochrome P-450 in primary cultures of human hepatocytes. When omeprazole was added to the culture medium in varying concentrations, there was an increase in P-450IA2 protein and mRNA concentrations, an increase in de novo synthesis of P-450IA2 protein, and an increase in microsomal catalytic activities characteristic of P-450IA2 (phenacetin deethylase and acetanilide hydroxylase). Omeprazole treatment also resulted in an increase in both enzymatic activity characteristic of P-450IA1 (ethoxyresorufin deethylase and benzpyrene hydroxylase) and concentration of P-450IA1 mRNA. In contrast, omeprazole appeared to have no significant effect on expression of other P-450s within the P-450II or P-450III families in the hepatocytes. To validate these in vitro observations, liver biopsy specimens were obtained from five patients before and after a 4-day course of pharmacological doses of omeprazole. In each patient, omeprazole treatment appeared to result in a two- to eightfold increase in P-450IA2 immunoreactive protein and P-450IA1 and P-450IA2 enzymatic activities. The authors conclude that omeprazole is an inducer of P-450IA2 and probably P-450IA1 in human liver. Induction of these enzymes could potentiate the bioactivation of carcinogens or the hepatotoxicity of some drugs such as acetaminophen.
High-dose inhaled terbutaline in the management of chronic severe asthma: comparison of wet nebulisation and tube-spacer delivery.
Authors: J G Prior, R V Nowell, G M Cochrane
Journal: Thorax (1982)

Eight patients with chronic severe asthma, poorly controlled by conventional doses of inhaled bronchodilator, were treated with high-dose inhaled terbutaline (4 mg four times daily), via either wet nebulisation of terbutaline respirator solution, or by tube-spacer aerosol, using cannisters delivering 1 mg terbutaline per metered dose. All patients improved objectively and subjectively on these higher dosage regimens during both day and night. A trial of high-dose inhaled beta2 sympathomimetic therapy should be considered in any patient with chronic severe asthma who fails to obtain benefit from standard doses of inhaled bronchodilator.
MEDICAL CARE FOR THE AGED
Authors: Charles D. Aring
Journal: JAMA (1961)

Considerable attention has been drawn to plans concerning compulsory health insurance for the aged under the Social Security System, or a "low cost health insurance protection" not under its aegis. I am uninformed on the financial and economic implications of plans such as these, but I have an opinion about the medical, social, and public health aspects of them by reason of forty years' work with the aged in large hospitals and medical schools over the country. Looking at matters under the aspect of eternity (as Spinoza said), I believe it unwise to single out a segment of the population for preference or for obloquy (depending on one's point of view) on grounds that will tend to isolate them, or in any way discourage their sense of responsibility. Beside the aged, there comes to mind the veteran, the orphan, the adolescent, the epileptic, etc., etc. Such classifications tend to insulate
Metal Sensitivity and Duodenal Ulcer
Authors: Barton L. Lewis
Journal: JAMA (1967)

To the Editor:—  Recently I have been impressed with a series of cases in which the presenting complaint was the common problem of metal sensitivity. These patients are for the most part sensitive to nickel, which is alloyed into a large number of metallic products which contact the skin, eg, jewelry, buckles, garters, and snaps. I have been impressed by the considerable number who have a history of active or healed duodenal ulcer (x-ray-proven). Whether this observation is true to the point of being able to withstand controlled study is difficult to say. Since our knowledge of the pathogenesis of duodenal ulcer is incomplete, conjecture regarding something more than a coincidence between the metal sensitivity and the ulceration could be useful and worthy of presentation.  Cross sensitivity reactions between contact dermatitis of the skin and the mucosa have been demonstrated, as in acrylic dermatitis due to dentures. Whether this mucosal
Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens.
Authors: D Vercelli, H H Jabara, K Arai, R S Geha
Journal: The Journal of Experimental Medicine (1989)

The induction of IgE synthesis by IL-4 requires T cells and monocytes, as well as T cell- and monocyte-derived cytokines. Optimal cytokine combinations, however, fail to induce highly purified B cells to secrete IgE, indicating that additional signals are required. We show herein that the induction of human IgE synthesis by rIL-4 requires cognate interaction between the T cell receptor/CD3 complex on T cells and MHC class II antigens on B cells: mAbs directed against these molecules completely blocked IL-4-dependent IgE induction. mAbs against cell adhesion molecules (CD2, CD4, LFA-1) also inhibited IgE synthesis induced by IL-4, confirming that cell-cell contact is necessary for IgE induction. The requirement for cognate T/B cell interaction was further shown by comparing the IgE-inducing ability of two human IL-4-producing alloreactive T cell clones: F6, which recognizes MHC class II antigens on both B cells and monocytes, and A1, which recognizes an HLA-DP-associated epitope expressed on monocytes, but not on B cells. When incubated with B cells and monocytes from a normal donor bearing the appropriate alloantigen, clone F6, but not clone A1, induced vigorous IgE synthesis, although both clones proliferated and secreted IL-4. Taken together, our results suggest that at least two, possibly synergizing, signals are required for the T cell-dependent induction of IgE synthesis by B cells: one signal is delivered by cognate T/B cell interaction, the other by T cell-derived IL-4.
Urinary tract infection in childhood: College guidelines inaccessible to GPs
Authors: A. D Short
Journal: BMJ (1993)

Responses of principals in general practice and trainees to question asking when they would refer childreni with uninary tract infections Girls Boys < 5 years ¢ 5 years < 5 years ¢ 5 years Principals (n=26): First infection 14 12 26 23 Second infection 11 12 3 Subsequent infections 1 2 Trainees (n= 6): First infection 4 3 5 5 Second infection 2 1 1 1 Subsequent infections 2replied (table).In the practice I audited five of 606 boys aged under 16 had had a urinary tract infection.Four of the five had been referred for investigation, all after the first documented episode, and four had had a repeat urine specimen sent for culture after treatment.More of the girls (12/58 1) had had a urinary tract infection, but only five had been referred for investigation, after a median of four episodes (range three to five); only two had had a urine specimen sent for culture after treatment.The eight other children had not been referred for investigation.