tbuckley/cabot-search huggingface dataset:
Estimating cardiovascular risk for primary prevention: outstanding questions for primary care
Authors: J. Robson
Journal: BMJ (2000)

Editorial by Jackson 

The recent joint British recommendations on the prevention of coronary heart disease, 1 the British Hypertension Society guidelines for the management of hypertension, 2 and comparable recommendations from the United States3 all conclude that the decision to start drug treatment in people at high risk but without cardiovascular disease should be based on their risk of coronary heart disease as estimated by the Framingham risk equations. We review some implications of their use in primary care.

#### Summary points

Prediction of coronary risk on the basis of multiple risk factors is more accurate than with any single factor alone

People with a 30% or greater risk of a coronary heart disease event in 10 years should be considered for treatment with aspirin, antihypertensives, and statins

Risk assessment for coronary heart disease should be routinely added to the existing screening programme for smoking and raised blood pressure

The measurement of serum lipid concentrations in all adults is not necessary for the identification of people at high risk

A national programme is required to support the identification and treatment of the 10% of the population who have coronary risks of 30% or more

For 50 years the Framingham heart study has documented blood pressure, smoking, lipid concentrations, and other characteristics of 5300 white men and women, together with their causes of death and disease.4 These data have been used to predict death or major vascular events.

It is important to be clear which outcome is being predicted and over what period. Expressed as risks at one, five, or 10 years the predicted outcomes include fatal and non-fatal coronary heart disease, 5 stroke, 6 and total cardiovascular disease including congestive cardiac failure and peripheral vascular disease.7 8 The risk of a coronary heart disease event in 10 years (myocardial infarction …
THE INFLUENCE OF CORTISONE ON PRIMATE MALARIA
Authors: L. H. Schmidt, Wanda L. Squires
Journal: The Journal of Experimental Medicine (1951)

Studies have been made of the effects of cortisone on the course of primary and developed infections with P. cynomolgi in the rhesus monkey. This investigation has shown that repetitive admmistration of the hormone in daily doses of 10 mg. per kg. during the primary attack produced striking intensification of the peripheral blood infection during the postcrisis phases of the disease. Similar administration of 10 or 50 mg. per kg. doses of the hormone during the chronic or latent stages of the infection provoked recrudescences of remarkable severity. In both early and late infections the responses induced by cortisone treatment corresponded closely to the reactions to splenectomy. Collateral studies have shown that the doses of cortisone which produced the reactions described above also evoked a lymphopenia, marked reductions in the sizes of the axillary and inguinal lymph nodes and spleen, and striking histological changes in the latter organ. These changes involved severe regression or exhaustion of lymphoid elements in both splenic nodules and pulp with almost complete obliteration of proliferative activities involved in the production of macrophages from lymphocytes. Indications are that the resulting reduction in supply of macrophages, rather than inhibition of phagocytic activity per se, was responsible for the intensification of the disease produced by cortisone.
Outbreaks of salmonella infection in hospitals in England and Wales 1978-87.
Authors: C. A. Joseph, S. R. Palmer
Journal: BMJ (1989)

A total of 248 outbreaks of salmonella infection in hospital affecting over 3000 patients and 110 associated deaths were ascertained in England and Wales in 1978-87, compared with 522 outbreaks of salmonella in 1968-77. The largest reduction was found in outbreaks from children's units and maternity units. Fifty seven (24%) outbreaks were considered to be due to foodborne salmonellosis, and 70 (30%) were reported as person to person spread of the infection. The psychiatric hospital was the type of hospital in which foodborne outbreaks most often occurred, but the risk of being affected in an outbreak not due to food seemed to be highest in maternity units. Better control of infection and better surveillance should lead to earlier investigation and control of outbreaks.
Mechanisms whereby a synthetic phosphatidyl-choline-specific phospholipase D (PCPD) activator overcomes multidrug resistance in human hepatocellular carcinoma cells
Authors: L MARUCCI
Journal: Hepatology (1995)

This chapter reviews the genetic studies that have provided new information on the biochemical and medical importance of CAAX-protein prenylation. The CAAX proteins undergo three sequential posttranslational processing steps: prenylation, endoproteolysis, and carboxyl methylation. These steps are mediated by four different enzymes: farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I), RAS converting enzyme 1 (RCE1), and isoprenylcysteine carboxyl methyltransferase (ICMT). Over the past 20 years, there has been an intense interest in understanding the biological significance of CAAX protein processing and its impact on CAAX protein stability, membrane targeting, protein–protein interactions, signaling, and function. The genetic studies with Fntb and Pggt1b conditional knockout alleles support the idea that farnesylation is essential for H-RAS membrane association and HDJ2 and prelamin A prenylation and that both farnesylation and geranylgeranylation are essential for fibroblast and keratinocyte proliferation in vitro. Knockout of Fntb alone and Pggt1b alone significantly impairs K-RAS-induced tumor growth in vivo despite the fact that K-RAS remains prenylated under both conditions. The results also support the idea that simultaneous inhibition of FTase and GGTase-I blocks K-RAS prenylation and could be therapeutically useful.
Treating Cushing's disease
Authors: W J Jeffcoate
Journal: BMJ (1988)

Treating Cushing's diseasePituitary dependent bilateral adrenocortical hyperplasia (Cushing's disease) is a rare and unpleasant condition.Before bilateral adrenalectomy was made possible by the advent of adrenal replacement treatment in the 1950s life expectancy was less than five years.'Although hazardous,2 bilateral adrenalectomy was the best treatment for many years.Indeed, it remains so in some cases, especially as morbidity and mortality can be reduced by preoperatively using drugs that block cortisol synthesis (metyrapone3 and aminoglutethimide4).The operation may be complicated by Nelson's syndrome,5 in which the adrenocorticotrophic hormone secreting adenoma of the pituitary enlarges and may occasionally become locally invasive and effectively incurable.Estimates of the risk of this happening vary from
Detection of occult cerebrospinal fluid involvement during maintenance therapy identifies a group of children with acute lymphoblastic leukemia at high risk for relapse
Authors: Carolina Martínez‐Laperche, Ana M. Gómez‐García, Álvaro Lassaletta, Cristina Moscardó, José L. Vivanco, Javier Molina, José L. Fuster, José M. Couselo, José Sánchez de Toledo, Encarnación Bureo, Luis Madero, Manuel Ramírez
Journal: American Journal of Hematology (2013)

We aimed at assessing the clinical significance of the levels of acute lymphoblastic leukemia (ALL) cells in samples of cerebrospinal fluid (CSF) during therapy. We studied 990 CSF samples from 108 patients, at the time of diagnosis (108) and at each time of intrathecal therapy (882). The proportions of leukemic cells in CSF samples were assessed by flow cytometry (FCM). Patients with central nervous system (CNS) involvement at diagnosis (FCM+) showed predominantly a T-ALL, and higher percentages of known negative prognostic factors: high risk group, higher white blood cell counts, normal karyotype, and the BCR-ABL fusion gene. No differences in relapse free survival (RFS) and overall survival (OS) were observed between FCM+ versus FCM- at diagnosis. Patients with CNS involvement during therapy showed significantly older age, and higher frequencies of T-cell leukemia. We found a significantly higher RFS in patients with FCM+ during therapy. The detection of subclinical CNS disease by FCM during maintenance was associated with significantly lower 3-years RFS and 3-years OS. A sensitive methodology like FCM can be applied for a close follow-up of the levels of ALL in CFS samples, and may identify a group of patients at high risk for relapse.
Gilles de la Tourette's Syndrome: Remission With Haloperidol
Authors: Marvin Boris
Journal: JAMA (1968)

<h3>To the Editor:—</h3> A syndrome comprised of motor tics and coprolalia was reported by Gilles de la Tourette in 1885.<sup>1</sup>Characteristically, the syndrome consists of numerous vocal and motor tics accentuated during times of emotional stress. Coprolalia occurs later and is considered a pathognomonic sign. The onset is usually between 5 and 10 years of age, and the prognosis almost uniformly poor. Psychotherapeutic and psychopharmacological measures employed have been of very little benefit.<sup>2-6</sup> In 1961, Seignot used haloperidol for Gilles de la Tourette's syndrome.<sup>7</sup>The patient was a 35-year-old man who had an estimated 1,000 tics a day and coprolalia since the age of 10 years, except for a period of two years in adolescence when he had spontaneous remission. Haloperidol decreased the patient's tics to two to three times per day, and completely alleviated the coprolalia. Four additional cases with marked beneficial response to haloperidol have
Motivational Factors in Abortion Patients
Authors: FRANCIS J. KANE, PETER A. LACHENBRUCH, MORRIS A. LIPTON, DAVID BARAM
Journal: American Journal of Psychiatry (1973)

Ninety-nine single white pregnant women seeking abortion were compared with 79 single nonpregnant women of similar background. Most of the women in both groups were college students. Of the pregnant group, 40 percent were found to have motivational factors that may have influenced the occurrence of the pregnancy, such as guilt over use of contraception, a severe acting-out character disorder, or reactions to loss. Psychological testing showed that the pregnant group rated themselves as more impulsive and as tending to externalize aggression. Knowledge of and access to contraception was similar in the two groups. The authors draw inferences from their study as to the most useful kinds of sex education programs colleges might undertake.
Physicians' role will change to meet patients' needs BMA wants national standards for community care (pounds sterling)300 000 allocated for research on medical education BMA backs EU commissioner's antismoking initiative Doctors can make computers work Government appoints commission on human genetic
Authors: L. Beecham
Journal: BMJ (1996)

# Physicians' role will change to meet patients' needs {#article-title-2}

District general hospitals will continue to play a major role in caring for patients who are acutely ill and need complex investigation and management. In its report Future Patterns of Care by General and Specialist Physicians the Royal College of Physicians recommends the retention of the acute general hospital serving between 200 000 and 300 000 people. The district general hospital of the future will provide care for the emergency admission and subsequent care of acutely ill patients round the clock.

The college says that in the medical disciplines at least 70–80% of beds are occupied by patients admitted urgently or as emergencies. In some district general hospitals the figure is nearer 95%—a figure which the college says must not be ignored in proposals for bed reductions.

The report says that while there has been a drift towards highly specialised physicians over the past two decades the balance is now returning towards the generalist. The college says that in the future both the general and specialist physician will need to play a key role in secondary care and suggests that there may also be a need for a new kind of physician with specific responsibilities for medical emergencies.

Physicians of the future are likely to work in teams with other healthcare workers, collaborating with general practitioners in following jointly developed guidelines, and in outreach clinics where appropriate.

As the hours worked by junior doctors fall more direct care will be delivered by consultants …
Loss of Insulin Signaling in Vascular Endothelial Cells Accelerates Atherosclerosis in Apolipoprotein E Null Mice
Authors: Christian Rask-Madsen, Qian Li, Bryn Freund, Danielle Feather, Roman Abramov, I-Hsien Wu, Kai Chen, Junko Yamamoto-Hiraoka, Jan Goldenbogen, Konstantinos B. Sotiropoulos, Allen Clermont, Pedro Geraldes, Claudia Dall'Osso, Amy J. Wagers, Paul L. Huang, Mark Rekhter, Rosario Scalia, C. Ronald Kahn, George L. King
Journal: Cell Metabolism (2010)
PREDICTORS AND PROGNOSIS OF SPONTANEOUS CORONARY ARTERY DISSECTION IN YOUNG WOMEN PRESENTING WITH STEMI
Authors: Amber Marie Otten, Jan Paul Ottervanger, Anita Kloosterman, Arnoud Hof, Marcel Gosselink, Jan-Henk Dambrink, Jan Hoorntje, Harry Suryapranata, Angela Maas
Journal: Journal of the American College of Cardiology (2013)
Circulating Tumor Cells in Metastatic Breast Cancer — Toward Individualized Treatment?
Authors: Stephan Braun, Christian Marth
Journal: New England Journal of Medicine (2004)

When Steven Paget published his theory of "seed and soil" in 1889,1 the idea of hematogenous tumor-cell dissemination was born. More than a century later, with the use of molecular tools, new clinical findings have resulted in explanations of hither-to unexplainable phenomena, such as that donor-derived cancer in recipient organ allografts2 and viable single tumor cells in secondary organs were both the descendants of a known primary tumor3 and the potential precursors of subsequent metastasis.4 Now, as shown by Cristofanilli et al.5 in this issue of the Journal, a laboratory assay of circulating tumor cells enables us to predict a . . .
The Treatment of Renal Failure: Therapeutic Principles in the Management of Acute and Chronic Uremia
Authors: Norman W. Carter
Journal: JAMA (1966)

The second edition of this well known book is somewhat larger than the first, having added 128 pages of text and 257 more references. The scope of the book remains much the same as in the previous edition. Introductory chapters deal with normal anatomy and renal function, and then two chapters discuss function in the diseased kidney and signs and symptoms of renal failure. The remainder of the book is largely taken up by two chapters of immediate importance in the care of a patient, "Diagnosis and Treatment of Acute Renal Failure" and "Treatment of Chronic Renal Failure." Merrill correctly stresses the need for a logical diagnostic approach to the patient with acute renal failure, and he includes specific examples. He proposes a thoughtful, conservative course, instead of a perhaps harmful diagnostic assault. Although he cites many references, the author gives no really critical discussion of the mechanisms of production
Abstract 2138: 6-Shogaol from dried ginger inhibits growth of prostate cancer cells both in vitro and in vivo
Authors: Achinto Saha, Jorge Blando, Eric Silver, Linda Beltran, Jonathan Sessler, John DiGiovanni
Journal: Cancer Research (2014)

Abstract Prostate cancer (PCa) is the most common non-cutaneous neoplasm and is the second leading cause of cancer death in American men. Approximately 1 in 6 men will be diagnosed with PCa during their lifetime and about 1 in 36 will die of PCa. It is estimated that approximately 238,590 new cases of PCa will be diagnosed and 29,720 PCa-related deaths will occur in the United States in 2013. 6-Shogaol (6-SHO), a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been shown to possess anti-inflammatory and anticancer activity. In the present study, the effect of 6-SHO on the growth of PCa cell lines was investigated. 6-SHO effectively reduced survival and induced apoptosis of cultured human (LNCaP, DU145 and PC3) and mouse (HMVP2) PCa cell lines. Mechanistic studies revealed that 6-SHO reduced constitutive and IL-6 induced STAT3 activation and inhibited both constitutive and TNF-α induced NF-κB activity in these cell lines. In addition, 6-SHO decreased the level of several STAT3 and NF-κB regulated target genes at the protein level (including cyclin D1, survivin and cMyc) and modulated mRNA levels of chemokine, cytokine, cell cycle and apoptosis regulatory genes (IL-7, CCL5, BAX, BCL2, p21 and p27). 6-SHO was more effective than two other compounds found in ginger, 6-gingerol and 6-paradol, at reducing survival of PCa cell lines and reducing STAT3 and NF-κB signaling. 6-SHO also showed significant tumor growth inhibitory activity in an allograft model using HMVP2 cells. Overall, the current results lead us to suggest that 6-SHO may have potential as a chemopreventive and/or therapeutic agent for PCa and that further study of this compound is warranted Citation Format: Achinto Saha, Jorge Blando, Eric Silver, Linda Beltran, Jonathan Sessler, John DiGiovanni. 6-Shogaol from dried ginger inhibits growth of prostate cancer cells both in vitro and in vivo. [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 2138. doi:10.1158/1538-7445.AM2014-2138
Abstract 2340: Ribonucleotide reductase subunit M2 promotes cell invasiveness and motility in lung and head and neck cancer cells
Authors: Mohammad Aminur Rahman, A.R.M. Ruhul Amin, Zhuo Georgia Chen, Mark E. Davis, Dong Moon Shin
Journal: Cancer Research (2011)

Abstract Ribonucleotide reductase subunit M2 (RRM2) has been frequently observed to be aberrantly overexpressed in various tumors. RRM2 is a key enzyme involved in the production of 2′-deoxyribonucleoside 5′-triphosphates required for DNA synthesis. In addition to DNA synthesis, it has been reported that RRM2 modulates cellular invasiveness. However, the mechanisms through which RRM2 affects the invasive phenotype have not been elucidated. In our study, we examined the role of RRM2 in cell invasion and migration of different lung (A549, H460 and H1299) and head and neck (Tu686) cancer cell lines. To explore the mechanism underlying RRM2's activity, we applied small interference RNA (siRNA) to knockdown the RRM2 protein while pcDNA3/RRM2 plasmid was used to establish RRM2 overexpressing stable cell lines. Our results revealed varying degrees of RRM2 expression levels in lung and head and neck cancer cell lines, which were proportionally correlated with the invasive capability of cells. H1299, a cell line that features epithelial-mesenchymal transition (EMT) expressed the highest level of RRM2 protein among the cell lines studied, and exhibited the greatest invasive and migratory abilities as demonstrated by Boyden chamber invasion and wound healing assays. H1299 was 6-fold more invasive than A549, which has lower RRM2 expression. Moreover, gain of function analysis demonstrated that overexpression of RRM2 enhanced cell invasiveness and motility in low RRM2-expressing cell lines A549 and Tu686. Western blots revealed that markers associated with tumor cell invasion and migration such as phospho-Src, phospho-FAK, phospho-calveolin-1, phospho-Akt, phospho-Erk, and MMP-9 secretion were induced whereas E-cadherin protein expression was significantly inhibited in RRM2 overexpressing cell lines. In contrast, loss of function analysis showed that siRNA targeting RRM2 decreased RRM2 expression and attenuated cellular invasiveness and motility in both lung and head and cancer cell lines. Our study demonstrated that RRM2 substantially promoted cell invasion and migration abilities. An elevated RRM2 may serve as a potential biomarker for metastasis of head and neck and lung cancer. Thus, targeting RRM2 and its downstream signaling intermediaries represents a rational approach for developing novel anticancer therapeutics. (This work is supported by grants from NIH U54CA119338-04, P50CA128613 and DOD W81XWH-07-1-0306). 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 2340. doi:10.1158/1538-7445.AM2011-2340
Blood Transfusion and Non-Hodgkin Lymphoma: Lack of Association
Authors: Johanna Adami
Journal: Annals of Internal Medicine (1997)

Background: Non-Hodgkin lymphoma is the seventh most commonly diagnosed malignant condition world-wide, and its incidence has increased markedly in recent decades. Blood transfusions have been implicated as a possible risk factor for non-Hodgkin lymphoma. Objective: To determine whether blood transfusions are associated with an elevated risk for non-Hodgkin lymphoma. Design: Population-based, nested case–control study. Setting: Nationwide cohort in Sweden. Patients: 361 patients with non-Hodgkin lymphoma and 705 matched controls, nested within a population-based cohort of 96 795 patients at risk for blood transfusion between 1970 and 1983. Prospectively collected information on exposure was retrieved from computerized transfusion registries. Measurements: Odds ratios obtained from conditional logistic regression models were used as measures of relative risks. Results: No association was found between blood transfusions and the risk for non-Hodgkin lymphoma when patients who had received transfusions were compared with patients who had not received transfusions (odds ratio, 0.93 [95% CI, 0.71 to 1.23]). A reduction in risk was seen among persons who received transfusion of blood without leukocyte depletion (odds ratio, 0.72 [CI, 0.53 to 0.97]). Risk was not related to number of transfusions, and no interaction was seen with latency after transfusion. Conclusion: The findings in this study do not support previous observations of an association between blood transfusions and the risk for non-Hodgkin lymphoma.
Challenges of Minimally Invasive Pancreas Surgery Growth With Such a High Learning Curve
Authors: Barish H. Edil, Richard D. Schulick
Journal: JAMA Surgery (2015)

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Eastern Europe and Russia face world's fastest growing HIV epidemic
Authors: Fiona Fleck
Journal: BMJ (2004)

Developing democracies in eastern Europe and the former Soviet Union are facing the world's fastest growing epidemic of HIV, according to a report published this month by the United Nations Development Programme.

If governments in the region fail to coordinate health, law and order, public information measures, and humanitarian concerns to tackle the growing crisis, the epidemic will be a severe brake on their economic and social development, the report concluded.

The report was released ahead of a three day conference in Dublin last week called “Breaking the barriers: the fight against HIV/AIDS in Europe and Central …