tbuckley/cabot-search huggingface dataset:
WHO calls for return to primary care to help ailing health systems
Authors: J. Zarocostas
Journal: BMJ (2008)

<h3>Abstract</h3> Nuclear envelope (NE) expansion must be controlled to maintain nuclear shape and function. ‘Closed’ mitosis occurs within an intact NE and thus, requires NE expansion. In the fission yeast <i>S. pombe</i> the expansion is underpinned by CDK1-dependent inactivation of the phosphatidic acid (PA) phosphatase lipin. Yet, how the lipin substrate PA and its product diacylglycerol (DG) are regulated in time and space and what are the implications of changes in their distribution for mitotic fidelity remain unknown. Using genetically encoded PA and DG probes, we show that DG levels drop dramatically at the NE during <i>S. pombe</i> mitosis. We demonstrate that DG-to-PA conversion catalysed by the diacylglycerol kinase Dgk1 is essential to reinforce the drop in DG levels at the NE, in addition to CDK1-dependent lipin inactivation. When DG levels do not decay, NE does not expand causing mitotic failure. Further experiments suggest that DG consumption fuels a spike in glycerophospholipid biosynthesis, controlling NE expansion, and ultimately, mitotic fidelity.
Doctors' antibiotic prescriptions should be scrutinised, says NICE
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Doctors should have their antibiotic prescribing scrutinised and told whether it is higher than average for their area or falls outside of recommended uses, draft guidelines have said. Prescribers also need to stand up to patients who demand antibiotics when they are not appropriate, the guidelines say.

The recommendations are part of the guidance on antimicrobial stewardship from the National Institute for Health and Care Excellence (NICE), which is open for consultation until 17 March.1 They will apply to anyone who prescribes antimicrobial medicines, although most antibiotic prescribing (79%) takes place in general practice.

The draft guidance recommends setting up multidisciplinary antimicrobial stewardship teams that work across all …
HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity
Authors: Daniele Pastori, Antonella Esposito, Roberto Carnevale, Simona Bartimoccia, Marta Novo, Alessandra Fantauzzi, Francesco Di Campli, Pasquale Pignatelli, Francesco Violi, Ivano Mezzaroma
Journal: Journal of Infection (2015)
Revenue allocation in the reorganized Health Service.
Authors: P H Gentle, J M Forsythe
Journal: BMJ (1975)

This paper recommends that the secrecy long associated with the allocation of Health Service revenue should be replaced by an objective formula applied to areas and districts. In this way the allocations should be "fairer" and the different tiers of management within the reorganized N.H.S. would have a greater incentive for the better use of their resources. The Department of Health and Social Security has demonstrated its desire to be frank and objective in revenue resource allocation and it new remains for the other tiers to follow suit.
Environmental Exposure to Lead and Children's Intelligence at the Age of Seven Years
Authors: Peter A. Baghurst, Anthony J. McMichael, Neil R. Wigg, Graham V. Vimpani, Evelyn F. Robertson, Russell J. Roberts, Shi-Lu Tong
Journal: New England Journal of Medicine (1992)

Exposure to lead in early childhood is thought to result in delayed neuropsychological development. As yet there is little longitudinal evidence to establish whether these effects persist into later childhood.We measured IQ scores in 494 seven-year-old children from the lead-smelting community of Port Pirie, Australia, in whom developmental deficits associated with elevated blood lead concentrations had already been reported at the ages of two and four years. Exposure to lead was estimated from the lead concentrations in maternal blood samples drawn antenatally and at delivery and from blood samples drawn from the children at birth (umbilical-cord blood), at the ages of 6 and 15 months and 2 years, and annually thereafter. Data relating to known covariates of child development were collected systematically for each child throughout the first seven years of life.We found inverse relations between IQ at the age of seven years and both antenatal and postnatal blood lead concentrations. After adjustment by multiple regression for sex, parents' level of education, maternal age at delivery, parents' smoking status, socioeconomic status, quality of the home environment, maternal IQ, birth weight, birth order, feeding method (breast, bottle, or both), duration of breast-feeding, and whether the child's natural parents were living together, the relation with lead exposure was still evident for postnatal blood samples, particularly within the age range of 15 months to 4 years. For an increase in blood lead concentration from 10 micrograms per deciliter (0.48 mumol per liter) to 30 micrograms per deciliter (1.45 mumol per liter), expressed as the average of the concentrations at 15 months and 2, 3, and 4 years, the estimated reduction in the IQ of the children was in the range of 4.4 points (95 percent confidence interval, 2.2 to 6.6) to 5.3 points (95 percent confidence interval, 2.8 to 7.8). This reduction represents an approximate deficit in IQ of 4 to 5 percent.Low-level exposure to lead during early childhood is inversely associated with neuropsychological development through the first seven years of life.
The Relative Effects of Left Ventricular Hypertrophy, Coronary Artery Disease, and Ventricular Dysfunction on Survival Among Black Adults
Authors: Youlian Liao
Journal: JAMA (1995)

To evaluate the effect of echocardiographically determined left ventricular hypertrophy (LVH) on survival in comparison with number of stenosed vessels and left ventricular systolic dysfunction.Cohort study based on a consecutive sample from a hospital registry, with a mean follow-up of 5 years.An inner-city public hospital in Chicago, Ill.The study included 1089 consecutive black patients who underwent both coronary angiography and M-mode echocardiography as part of a diagnostic evaluation.Nonstenosed coronary arteries, single-vessel disease, and multivessel disease were found in 48%, 16%, and 36% of patients, respectively; LVH (left ventricular mass index > 131 g/m2 in men and > 100 g/m2 in women) was detected in 50% of patients. Hypertrophy without coexistent obstructive coronary disease was associated with a lower survival rate than that observed for single-vessel disease and was similar to multivessel disease. When LVH, number of diseases vessels, and left ventricular dysfunction were subjected to multivariate analysis, hypertrophy conferred a relative risk (RR) of 2.4 (95% confidence interval [CI], 1.7 to 3.2). By comparison, the presence of a single stenosed vessel did not increase the risk of death. Multivessel disease and ejection fraction less than 45% were associated with an RR of 1.6 (95% CI, 1.1 to 2.2) and 2.0 (95% CI, 1.4 to 2.7), respectively. Calculation of the attributable risk fraction demonstrated that for every 100 deaths in this cohort, LVH independently accounted for 37. The corresponding attributable risk fractions were 1%, 22%, and 9% for single-vessel disease, multivessel disease, and ventricular dysfunction, respectively.Left ventricular hypertrophy was associated with a greater RR and attributable risk than the traditional measures of coronary disease severity. The high prevalence and powerful risk of LVH make an important contribution to the adverse survival rates among black patients with heart disease and may account for much of the black-white differential.
Androgen Receptor Expression in Breast Cancer with Special Relation to Triple-Negative Molecular Phenotype and its Response to Anterior Chemotherapy
Authors: A.A. Agarwal, A.A. Sonkar, J.K. Kushwaha, N. Hussain, K. Gaurav, R. Gupta, A. Singh, Y. Dheer
Journal: Annals of Oncology (2013)
Pathologists: Servants or Colleagues?
Authors: Renato Baserga
Journal: New England Journal of Medicine (1973)

I have a friend who in the past two years has served as a chronic consultant for pathology search committees. As a former chairman of a department of pathology, with no desire for seeking another chair (the electric chair, he called it), he is considered the proper authority on the future of pathology and on prospective candidates for a chairmanship, presumably for the same reasons for which a retired courtesan is considered an authority in matters of love. He tells me that his experience with pathology search committees has been rather depressing. In the first place, he says, surgeons and . . .
Marfan's Syndrome
Authors: Edward S. Bear
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Lee's points are well taken and possibly we should have stated that the diagnosis of Marfan's syndrome was<i>suggested</i>rather than<i>warranted</i>by our findings. Until a more precise definition of a basic defect (as in homocystinuria) is demonstrated in Marfan's syndrome, there will continue to be confusion surrounding incomplete or forme fruste cases. A recent example is a case of Marfan's syndrome with chronic atrial flutter<sup>1</sup>which failed to exhibit ocular disease, positive family history, or what Lee would call "typical aortic disease." The abnormality in the small coronary arteries of patients with Marfan's syndrome as described by James et al<sup>2</sup>must make one highly suspicious of Marfan's syndrome in a patient with arachnodactaly and a cardiac conduction defect. Sinclair has mentioned cataracts in Marfan's syndrome, but is not clear if they were in association with ectopia lentis or not.<sup>3</sup>Our patient was believed to
THE DIAGNOSIS OF ENLABGED BBONCHIAL LYMPH NODES.
Authors: ALFRED FRIEDLANDER
Journal: JAMA (1905)

Among the phenomena of the developmental period of childhood, there is none more striking perhaps, than the activity for the lymphatic system. The lymph glands constitute an apparatus for filtration. Given the factors of rapid growth, on the one hand, and of poorly developed powers of resistance, on the other, and it can readily be seen that the period of childhood must necessarily be accompanied by marked reactive irritation and inflammation of the entire glandular system. During this period the mucous membranes are prone to irritation, with resulting inflammation. Added to this, there is the disposition, often hereditary, not infrequently aggravated by faulty conditions of development and hygiene, to chronic inflammation of mucous membrane, skin and bone. Under such conditions it is not surprising that the filter system should be taxed to its utmost capacity—hardly less astonishing that we should find very often, in the inability
Hormonal Contraceptives and Arterial Thrombosis — Not Risk-free but Safe Enough
Authors: Diana B. Petitti
Journal: New England Journal of Medicine (2012)

The link between combined estrogen–progestin oral contraceptives and venous and arterial thrombosis was made soon after these products were marketed, in the early 1960s.13 By 1970, the doses of estrogen in combined estrogen–progestin oral contraceptives had already been lowered on the basis of epidemiologic data showing that formulations with higher estrogen doses were associated with increased vascular risks.4 Studies published in 1995 and 1996 showed that increases in the risk of venous thromboembolism were greater with newly marketed estrogen–progestin oral-contraceptive formulations containing desogestrel and gestodene than with formulations containing levonorgestrel and other “older” progestins.58 Much attention has since . . .
An everyday story of ICU folk
Authors: G. Baldock
Journal: BMJ (1995)

In many ways intensive care flies in the face of the current philosophy of health care delivery. It provides expensive rescue care to a small number of people, of whom a substantial minority do not benefit, with minimal impact on the health of communities; and evidence to support many of the treatments given is lacking. Every day those working in intensive care units face head on the results of the tension between changing demography, advancing technology, and limited resources. Given the importance ascribed to involving the public in decisions over priorities in health care, it is important that television programmes on health matters convey the issues entailed in ways that are easily understood yet do not oversimplify or trivialise them. How does the series Intensive Care succeed?

The choice of setting—the adult intensive …
Recombinant human interleukin-11 improves thrombocytopenia in patients with cirrhosis
Authors: Reem Ghalib, Cheryl Levine, Manal Hassan, Tricia McClelland, John Goss, Risë Stribling, Philip Seu, Yehuda Z. Patt
Journal: Hepatology (2003)

To elucidate the hematopoietic activity of recombinant human interleukin–11 (rhIL–11, [Neumega, Cambridge, MA]) in patients with cirrhosis and thrombocytopenia, we administered rhIL–11 at 50 μg/kg/d subcutaneously to 10 patients for 10 days with a 30–day follow–up period. All treated patients (n = 9) experienced a gradual, yet significant increase in their platelet count above the baseline value ( P ≤ .01) reaching the peak value (median, 93,000/μL; range, 60,000–206,000/μL) at a median of 13 days (range, 6–23 days). Eight patients (89%) had a significant increase of ≥50% over the baseline value ( P &lt; .05). Moreover, further increases to ≥60,000/μL, ≥80,000/μL, and ≥100,000/μL were observed in 100%, 78%, and 33% of the patients, respectively. A subsequent decline in platelet count was observed at a median of 19 days (range, 7–26 days) after the occurrence of peak concentration. A significant increase in neutrophil count was also demonstrated starting on the third day of treatment ( P ≤ .01). Concurrent with an increase in the serum level of fibrinogen, transaminase levels declined significantly during treatment period, while bilirubin levels continued to drop for up to 20 days after the initiation of treatment ( P &lt; .05). The most frequent effects were due to plasma volume expansion, including conjunctival redness and edema. In conclusion, rhIL–11 can improve platelet counts in patients with early cirrhosis and these patients could benefit from rhIL–11 treatment. However, given the high frequency of regimen–related toxicity, the use of rhIL–11 in patients with cirrhosis should be administered with caution.
Treatment of Advanced Mammary Cancer
Authors: R. B. Welbourn, J. Ian Burn
Journal: New England Journal of Medicine (1972)

ABOUT 25 per cent of all women treated for cancer of the breast are cured. The remaining 75 per cent require at some stage treatment for incurable disease. These patients, whom we designate as having advanced mammary cancer, fall into four categories.Symptomatic Metastases without Local RecurrenceIn the first category are those in whom after treatment by mastectomy, symptomatic metastatic disease subsequently develops without evidence of local recurrence. This complication occurs in about three of every five women undergoing mastectomy and represents the most usual type of advanced disease. Skeletal deposits predominate, but hepatic, pulmonary and cerebral deposits are . . .
Hypomastia and Mitral-Valve Prolapse
Authors: Carol A. Rosenberg, Gordon H. Derman, William C. Grabb, Andrew J. Buda
Journal: New England Journal of Medicine (1983)

THE pathogenesis of mitral-valve prolapse is unclear. However, it has been associated with thoracoskeletal abnormalities,1 , 2 connective-tissue disorders,3 4 5 and coagulopathies.6 Affected tissues in these disorders are embryologically derived from mesenchymal-cell origins. During the sixth week of fetal life, the mitral valve undergoes embryologic differentiation, and the vertebral column and thoracic cage develop their shape and form through chondrification.7 , 8 The breast, which in large part is of mesenchymal origin, undergoes primordial development during the same time. Since both the breast and mitral valve are of mesenchymal origin, we postulated that an association may exist between breast-size development and mitral-valve prolapse. If present, . . .
Downregulation of polymeric immunoglobulin receptor and secretory IgA antibodies in eosinophilic upper airway diseases
Authors: C. Hupin, P. Rombaux, H. Bowen, H. Gould, M. Lecocq, C. Pilette
Journal: Allergy (2013)

Background Immunoglobulin (Ig) A represents a first-line defence mechanism in the airways, but little is known regarding its implication in upper airway disorders. This study aimed to address the hypothesis that polymeric Ig receptor (pIgR)-mediated secretory IgA immunity could be impaired in chronic upper airway diseases. Methods Nasal and ethmoidal biopsies, as well as nasal secretions, were collected from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP), allergic rhinitis (AR) and controls, and assayed for IgA1/IgA2 synthesis, pIgR expression, production of secretory component (SC), IgA and relevant IgA antibodies, and correlated with local eosinophils and inflammatory features (IL-12, IL-13 and ECP). Results pIgR expression was decreased in the ethmoidal mucosa in patients with CRSwNP (P = 0.003) and in AR (P = 0.006). This pIgR defect was associated with reduced levels of SC (P = 0.007) and IgA antibodies to Staphylococcus aureus enterotoxin B (SAEB) (P = 0.003) in nasal secretions from patients with CRSwNP, and with increased IgA deposition in subepithelial areas. pIgR downregulation was selectively observed in patients with tissue eosinophilia, whilst no clear relation to smoking history was observed. Conclusion Epithelial pIgR expression is decreased in patients with CRSwNP and AR and results in decreased SC and IgA antibodies to certain bacterial antigens (SAEB) in nasal secretions of patients with CRSwNP in parallel to subepithelial accumulation of IgA. This defect in mucosal immunity is associated with eosinophilic, Th2-related inflammation.
Putting palliative care on the global health agenda
Authors: Richard A Powell, Faith N Mwangi-Powell, Lukas Radbruch, Gavin Yamey, Eric L Krakauer, Dingle Spence, Zipporah Ali, Sharon Baxter, Liliana De Lima, Ali Xhixha, M R Rajagopal, Felicia Knaul
Journal: The Lancet Oncology (2015)
Abstract 5443: A novel biosensor for monitoring intracellular cGMP in live cells
Authors: Yanjie Sun, Adam B. Keeton, Heather N. Tinsley, Braeden L. Butler, Brock F. Binkowski, Gary A. Piazza
Journal: Cancer Research (2011)

Abstract The second messenger, cyclic guanosine 3’, 5’-monophosphate (cGMP) is a critical and multifunctional signaling molecule involved in many cellular processes. Intracellular cGMP is synthesized by guanylyl cyclase (GC) and is degraded by various phosphodiesterase (PDE) isozymes. Increased levels of cGMP can activate cGMP-dependent protein kinase (PKG), modulate cGMP-gated ion channels, or affect PDE activity. Since cGMP plays an important physiological role and may also be involved in various pathological conditions, including cancer, CNS disorders, and vascular deficiencies, cGMP-specific PDE isozymes represent an important class of drug targets. In order to measure intracellular cGMP levels in live cells, we constructed a novel genetically encoded cGMP biosensor with cGMP binding domains (from human PDE5A GAF-A domain) fused to a modified firefly luciferase. A lipid based reagent was used to transiently transfect HEK293 with this biosensor. Cells were then treated with the nitric oxide donors, sodium nitroprusside (SNP) or NOR-3, which are known to activate soluble GC. Bioluminescence was measured every 2 minutes for at least 60 minutes following treatment. Both SNP (50 µM) and NOR-3 (100 µM) caused a 3-fold increase in bioluminescence compared with vehicle treated cells, reaching a maximum within 10 to 20 minutes of compound addition. Co-transfection with soluble GC further increased the response up to 13-fold following SNP treatment. In addition, PDE inhibitors such as, zaprinast, dipyridamole and 3-isobutyl-1-methylxanthine amplified the response to SNP treatment. As expected, co-transfection with PDE5A decreased the basal level of cGMP and increased the sensitivity of the cGMP response to zaprinast and SNP, as well as the combination. These results suggest that this cGMP biosensor can be useful for studying drug effects on cGMP signaling in live cells. Methods to use the assay for high throughput screening are also being developed. Funding provided by NIH/NCI grants CA131378 and CA148817. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5443. doi:10.1158/1538-7445.AM2011-5443
THERAPEUTICS OF INFLAMMATION.
Authors: WARREN B. HILL
Journal: JAMA (1899)

This subject would indicate a paper of wide scope and the consideration of a matter which has often been thoroughly aired and discussed. I do not wish, however, to weary you with any generalities, but rather to take up some forms and conditions of inflammation which will interest you as dentists, as well as practitioners of medicine. As was suggested here last year, there is a common ground upon which dentists and doctors may meet, and the therapeutics of inflammatory conditions about the mouth, though a place oftentimes studiously avoided by both professions, should be cultivated in common by both. I do not wish to enter into a controversy as to the definition of inflammation, but will merely state that my remarks have to do more particularly with the pathologic condition characterized by an exaggeration of physiologic function in which engorgement and pain are the two characteristic symptoms.
Range-gated pulsed Doppler echocardiographic diagnosis of supracardiac total anomalous pulmonary venous drainage.
Authors: J Skovránek, S Tůma, D Urbancová, M Samánek
Journal: Circulation (1980)

Three patients with total anomalous pulmonary venous drainage (TAPVD) into the innominate vein were studied by using M-mode and pulsed Doppler echocardiography. An abnormal continuous flow towards the transducer in a suprasternal notch position detected by pulsed Doppler echocardiography in the left hemithorax leftward of the aortic echo is a sign of blood flow through the left vertical vein into the innominate vein. This finding is highly specific for TAPVD. High-velocity flow across the tricuspid valve, disturbed flow in the right pulmonary artery and abnormal flow in the left atrium are additional important pulsed Doppler echocardiographic findings in TAPVD. Right ventricular enlargement and paradoxical interventricular septal motion by M-mode echocardiography were not specific enough to distinguish TAPVD from other right ventricular volume overload lesions. An echo-free space posterior to the left atrium was not recorded.
Gender and the Professional Predicament in Nursing
Authors: M. Carpenter
Journal: BMJ (1995)

Celia Davies, Open University Press, pounds sterling12.99, pp 220, ISBN 0 335 19402 8

Nurses have always borne a double burden in relation to governmental and medical power: subordinated and undervalued as carers in a system with a curative bias, and oppressed as women within a system of male dominance. The times, however, have been changing, in response to the revaluation of biomedicine's contribution to health and the challenge of modern feminism. These two forces came together in 1986 in the proposed reform of nursing education, Project 2000, the implementation of which is currently reshaping the nature of nursing.

Celia Davies, …
LEFT VENTRICULAR HYPERTROPHY IN ATHLETES IS CHARACTERISED BY SUPERNORMAL MYOCARDIAL BLOOD FLOW RESERVE PREDOMINANTLY DUE TO IMPROVED CAPILLARY RECRUITMENT AS ASSESSED by quantitative MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY
Authors: Rajesh Chelliah, Greg Whyte, Sanjay Sharma, Antonis Pantazis, Roxy Senior
Journal: Journal of the American College of Cardiology (2013)