tbuckley/cabot-search huggingface dataset:
Abandoning Presumptive Antimalarial Treatment for Febrile Children Aged Less Than Five Years—A Case of Running Before We Can Walk?
Authors: Mike English, Hugh Reyburn, Catherine Goodman, Robert W Snow
Journal: PLoS Medicine (2008)

Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five.
A case of infantile digital fibromatosis showing spontaneous regression
Authors: N. ISHII, K. MATSUI, S. ICHIYAMA, Y. TAKAHASHI, H. NAKAJIMA
Journal: British Journal of Dermatology (1989)

A case of infantile digital fibromatosis (IDF) in a 3-year-old girl is reported. Two tumours were present on the left fourth toe and one over the lateral aspect of the left heel. Histological examination revealed that the tumour cells contained intracytoplasmic inclusion bodies, characteristic for this condition. The tumours showed spontaneous regression without therapy.
Imaging Synaptic Activity in Intact Brain and Slices with FM1-43 in C. elegans, Lamprey, and Rat
Authors: Alan R Kay, Aixa Alfonso, Simon Alford, Hollis T Cline, Andrea M Holgado, Bert Sakmann, Vladislav A Snitsarev, Thomas P Stricker, Michiko Takahashi, Ling-Gang Wu
Journal: Neuron (1999)
Controversies in the Management of Lymphomas, Including Hodgkin's Disease
Authors: David S. Rosenthal
Journal: JAMA (1984)

Classification, diagnostic tools, and therapeutic alternatives for the malignant lymphomas present a fruitful field for research, as well as controversy, to the clinical investigator. This volume of Cancer Treatment and Research focuses on at least six major dilemmas in the study of Hodgkin's disease and non-Hodgkins lymphomas (NHLs).  The individually authored 13 chapters debate issues such as (1) What is the origin of the Reed-Sternberg cell? (2) Is lymphangiography a necessary procedure in staging or has it been totally replaced by computed tomography? (3) Is radiation therapy or chemotherapy or combination of radiation therapy and chemotherapy the best treatment for limited stages of Hodgkin's disease (stages I to III)? (4) Is Rappaport's classification of the NHLs useful for the clinician in deciding on therapy? (5) Is nodular mixed NHL a subset that is more favorably treated? and (6) Should low grade or favorable NHL be treated conservatively, aggressively, or not
Mitral valve prolapse and coronary artery disease. Clinical, hemodynamic, and angiographic correlations.
Authors: J M Aranda, B Befeler, R Lazzara, A Embi, H Machado
Journal: Circulation (1975)

Among 95 patients with angina pectoris and angiographically documented coronary artery disease (CAD), prolapse of the scallops of the posterior leaflet of the mitral valve (PLMV) was noted in 30 patients. Left ventriculograms in the right anterior oblique (RAO) projection revealed isolated prolapse of the posteromedial commissural scallop (PMCS) in 12 patients and the anterolateral commissural scallop (ALCS) in two patients. Seven patients had prolapse of both PMCS and ALCS, three had prolapse of the PMCS and middle scallop (MS), and six had prolapse of all three scallops of the PLMV. Left ventricular dilatation with increase trabeculations was observed in 19 patients. Contractility determined in a quantitative fashion by segmental motion analysis was markedly impaired in 29 patients. None of the patients had angiographic evidence of mitral insufficiency. Left ventricular dysfunction was documented in 28 patients by either elevated left ventricular end-diastolic pressure (LVEDP), low cardiac index (CI) or decreased ejection fraction (EF). In two patients in whom left ventricular contractility improved after aortocoronary by pass, previously prolapsed scallops could not be identified in the postoperative ventriculogram. Prolapsed PLMV is a frequent angiographic finding in patients with angiographically observed CAD. Impaired contractility of the ventricular myocardium and papillary muscles, left ventricular dilatation, and hypertrophy appear to play a significant role in the pathogenesis of this abnormality through distortion of the directional axis of the papillary muscles, asynergic contraction of the related free wall of the left ventricle, and changes in the normal spatial alignment necessary for mitral valve closure. The syndrome of papillary muscle dysfunction in patients with coronary artery disease represents a wider clinical spectrom than previously described.
Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation.
Authors: O Olakanmi, S E McGowan, M B Hayek, B E Britigan
Journal: Journal of Clinical Investigation (1993)

Alveolar macrophages (AM) from smokers contain a much higher quantity of intracellular iron than AM from nonsmokers. Since some forms of iron will catalyze the formation of hydroxyl radical (.OH) from superoxide and hydrogen peroxide, the ability of AM derived from smokers and nonsmokers to generate .OH was assessed. No detectable .OH was produced by AM from either source, suggesting that iron sequestration by AM may limit the potential for .OH-mediated lung injury. Consistent with this hypothesis, the ability of bronchoalveolar lavage fluid (BAL) from smokers and nonsmokers to act as an .OH catalyst decreased after exposure to AM. We found that, like AM, human monocyte-derived macrophages (MDM) have the ability to acquire large quantities of iron from small low molecular weight iron chelates as well as decrease the ability of BAL to act as a .OH catalyst. When MDM or AM were exposed to the iron chelates or BAL they were then able to generate .OH after phorbol myristate acetate stimulation. However, when acutely iron-loaded or BAL-exposed MDM were placed in culture, their ability to produce .OH decreased with time to the level of non-iron-exposed controls. This process correlated with iron translocation from the plasma membrane to the cytosol as well as a 3-9-fold increase in cellular ferritin. No increase in antioxidant enzyme levels or induction of the heat shock response was observed. Iron sequestration by macrophages may protect nearby cells from exposure to potentially cytotoxic iron-catalyzed oxidants such as .OH.
Dutch doctors to receive more clarity over use of advance euthanasia directives for patients with dementia
Authors: T. Sheldon
Journal: BMJ (2013)

Senior figures in Dutch medicine and politics are set to decide whether advanced euthanasia directives can, in practice, replace verbal requests if patients with dementia are no longer able to express their wishes.

Doctors in the Netherlands have expressed “difficulties” with this “grey area,” arguing that some communication is essential if they are to understand properly their patients’ suffering and wishes.

But eminent figures in medical ethics argue that doctors are placing themselves above the 2002 euthanasia law. This law states that doctors can act on an earlier advanced directive once a patient becomes incompetent. …
Smoking and Deaths between 40 and 70 Years of Age in Women and Men
Authors: Stein Emil Vollset, Aage Tverdal, Håkon K. Gjessing
Journal: Annals of Internal Medicine (2006)

Background: The vast scientific literature on smoking and health contains few large studies with direct estimates of long-term mortality by smoking habits. Data have been lacking, particularly for women. Objective: To study smoking and deaths and causes of death in women and men of middle age (40 to 70 years of age). Design: Population-based cohort study. Setting: Norway (the Norwegian Counties Study). Participants: 24 505 women and 25 034 men who were born between 1925 and 1941. Measurements: Initial information on smoking habits was collected between 1974 and 1978. Smoking status was also assessed about 5 years and 10 years after the first examination. Death during 1974 to 2000 was studied by using death certificate information. Results: During follow-up, 2333 women and 4680 men died in middle age. Among women and men, 9% and 14% of never smokers, respectively, and 26% and 41% of continuing heavy smokers (≥20 cigarettes per day), respectively, died in middle age. Years of life lost among heavy smokers between 40 and 70 years of age were 1.4 years in women and 2.7 years in men, compared with never smokers. Rates of smoking-associated lung cancer were similar in women and men, while lower cardiovascular mortality rates in women explained most of the difference in smoking-associated all-cause mortality between men and women. Limitations: Data on changes in smoking habits after the baseline examination were not available for all participants and for the last 15 years of follow-up. Mortality levels in middle age may not apply to non-Norwegian populations. Conclusions: Continuing smoking strongly increased and smoking cessation decreased the risk for death between 40 and 70 years of age for both women and men. Despite similar rates for lung cancer death, women who smoked had lower mortality rates in middle age than men with similar smoking histories due to fewer cardiovascular deaths in women.
Once-weekly Rifapentine-containing Regimens for Treatment of Tuberculosis in Mice
Authors: JACQUES GROSSET, NACER LOUNIS, CHANTAL TRUFFOT-PERNOT, RICHARD J. O'BRIEN, MARIO C. RAVIGLIONE, BAOHONG JI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The bactericidal activities of several once-weekly rifapentine (P)-containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyrazinamide (Z) in a mouse experiment. Mice were infected intravenously with 1.3 × 107 cfu of M. tuberculosis strain H37Rv, and 8 wk of treatment began on Day 14 after infection, when mice were randomly allocated to an untreated control group and nine treatment groups of 30 mice each. At the end of 8 wk of treatment, all the tested regimens showed promising bactericidal activities. Once-weekly P alone was less bactericidal than six-times-weekly R alone; likewise, the once-weekly P-containing combined regimens were less bactericidal than the six-times-weekly standard regimen. However, the difference in killing was about 1 log10, which represented only a fraction of the overall 4 log10 to 5 log10 magnitude of killing effects. The addition of streptomycin (S) improved the bactericidal effect of once-weekly PHZ, and the effect of once-weekly PHZS was further enhanced when it was preceded by 2 wk of daily HZS. The latter regimen achieved the same level of activity as the standard six-times-weekly regimen. All of the once-weekly P-containing combined regimens were able to prevent the selection of R-resistant mutants, whereas monotherapy with R or P selected resistant mutants in approximately 50% of animals.
Pseudomonas fluorescens cross-infection due to contaminated humidifier water.
Authors: P J Redding, P W McWalter
Journal: BMJ (1980)

properties at high blood concentrations.MacLeod and Lamberts3 have shown the dopamine agonist effects of high concentrations of haloperidol and pimozide on prolactin release.Seeman4 has shown that very high concentrations of some antipsychotic drugs may enhance presynaptic release of neurotransmitters, including dopamine.Altematively, at high concentrations of antipsychotic drugs maximal dopaminergic blockade may occur.Additional dosage increments would not produce further dopamine blockade, but other pharma- cological effects, such as anticholinergic activity, might continue to increase and might be responsible for the presentations described.Toxic psychoses have been associated with high doses of anticholinergic drugs,5 usually combined with moderate doses of antipsychotic drugs.The episodes reported in these studies also appear to have been characterised by excitement and aggression, as in our cases.Requests for reprints to Dr Bridges.1 Barnes TRE, Roy DH, Gaind R. Open study to determine appropriate maintenance dosage of pimozide in patients with chronic schizophrenia.
Heparin-Induced Thrombocytopenia Presenting as Bilateral Adrenal Hemorrhages
Authors: Theodore E Warkentin, Eric L Safyan, Lori-Ann Linkins
Journal: New England Journal of Medicine (2015)

Drug Administration in 2005 as a topical 5% gel (50 mg of dapsone per 1 g of product; Aczone, Allergan).After the topical application of dapsone gel, a plasma level is detectable within 2 hours and has a half-life of 48 hours. 2 Our patient had been applying a pea-sized amount of topical dapsone twice daily for 7 days before presentation.Details of the mechanism of dapsone-induced methemoglobinemia and a discussion of other possible contributing factors in this patient's case are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.Our case report highlights the potential for systemic absorption with clinical methemoglobinemia after prescribed therapeutic use of a topical dapsone-containing product.
Heterozygous Lipoprotein Lipase Deficiency
Authors: Børge G. Nordestgaard, Susanne Abildgaard, Hans H. Wittrup, Rolf Steffensen, Gorm Jensen, Anne Tybjærg-Hansen
Journal: Circulation (1997)

Patients with mutations on both alleles of the lipoprotein lipase gene resulting in complete lipoprotein lipase deficiency exhibit the chylomicronemia syndrome with severe hypertriglyceridemia and increased risk of pancreatitis and possibly of ischemic heart disease. This study examined frequency, lipid levels, and risk of ischemic heart disease for heterozygous carriers of lipoprotein lipase mutations known to cause the chylomicronemia syndrome in the homozygous state.Two mutations were screened for in 9259 individuals in a general population sample and in 948 patients with verified ischemic heart disease. The percent frequencies of heterozygous individuals with the Gly188-->Glu and Ile194-->Thr substitutions in the general population were 0.06% (95% CI, 0.04% to 0.23%) and 0% (95% CI, 0.00% to 0.12%), respectively. The Gly188-->Glu substitution was associated with an increase in plasma triglycerides of 0.8+/-0.3 mmol/L (mean+/-SEM) and a decrease in plasma HDL cholesterol, apo A-I, and glucose levels of 0.45+/-0.07 mmol/L, 17+/-6 mg/dL, and 1.1+/-0.2 mmol/L, respectively. On multiple logistic regression analysis allowing for age, sex, plasma cholesterol, plasma lipoprotein (a), hypertension, diabetes mellitus, smoking, and body mass index, both plasma triglycerides and HDL cholesterol levels were independent predictors of ischemic heart disease. Finally, the Gly188-->Glu substitution was more common among patients with verified ischemic heart disease (percent frequency of heterozygous individuals, 0.32%) than among individuals from the general population (odds ratio, 4.9; 95% CI, 1.2 to 19.6). The effects of the Gly188-->Glu substitution were more pronounced than those of the common Asn291-->Ser substitution.Heterozygous lipoprotein lipase deficiency due to the Gly188-->Glu substitution appears to increase plasma triglycerides and reduce HDL levels and may thereby predispose carriers to ischemic heart disease.
Measuring Health Outcomes — Putting Gains into Perspective
Authors: Allan S. Detsky, Donald A. Redelmeier
Journal: New England Journal of Medicine (1998)

Patients, providers, payers, politicians, and the public are keenly interested in evaluating the worthiness of diverse health care interventions. Sometimes the attention is focused on existing interventions (such as childhood immunizations); at other times the attention is on potential interventions (such as an AIDS vaccine). The evaluations are often problematic because the magnitude of changes in health outcomes is difficult to interpret. And most health care and safety interventions yield only small changes in the health of populations despite causing dramatic changes in the health of some patients.Researchers often assess health outcomes by counting adverse events (e.g., deaths and . . .
1172-76 Healthcare costs for cardiovascular disease in women with and without obstructive coronary disease: Results from the National Institutes of Health-National Heart, Lung, and Blood Institutes-Sponsored Women's Ischemia Syndrome evaluation (WISE)
Authors: Leslee J Shaw, Barry L Sharaf, B.Delia Johnson, George Sopko, Carl J Pepine, Gerry Pohost, Steve Reis, William Rogers, Sheryl F Kelsey, C.Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2004)
Guidance Concerning Surgery for Emphysema
Authors: Jeffrey M. Drazen, Arnold M. Epstein
Journal: New England Journal of Medicine (2003)

Pulmonary emphysema is an irreversible condition resulting from the destruction of alveolar septa in the lung. There has been no effective treatment for emphysema that has progressed to the point at which substantial air-space destruction has occurred. Since emphysema takes your breath and exercise capacity away, without any hope that they will return, there was almost unbridled enthusiasm when a surgical procedure was devised to reverse some of the devastating effects of the disease.As detailed in a previous editorial,1 this procedure, known as lung-volume–reduction surgery, offered hope of enhanced survival and symptomatic relief to many patients with emphysema. In . . .
12High density lipoproteins exert pro-inflammatory effects on macrophages via IKK2- and NIK-independent NF-kB activation
Authors: EPC Van Der Vorst, K Theodorou, J Plat, M Van Eck, KA Rye, CA Bursill, SW Tas, MPJ De Winther, EAL Biessen, MMPC Donners
Journal: Cardiovascular Research (2014)

High-Density Lipoproteins (HDLs) have potent anti-inflammatory effects in various cell types. However, little is known about effects of HDLs on macrophages, key immune cells in atherosclerosis. In this study we aim to elucidate HDLs effects on macrophage inflammatory responses. Pre-incubation of human and murine macrophages with human reconstituted (apolipoproteinA-I/phosphatidylcholine) or native HDLs significantly decreased LPS-induced anti-inflammatory IL-10 production, while the opposite was observed for the pro-inflammatory mediators IL-12 and TNF-α. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages of human ApoA-I transgenic mice, which have high circulating HDLs levels. Stimulation with TLR7 ligand R848 showed similar effects both in vitro and in vivo, indicating that the observed effects are not TLR4 specific. Luciferase reporter assays and NF-κB target gene expression analyses showed that the pro-inflammatory HDLs effects in macrophages were mediated by NF-κB. However, IKK2-/- and NIK-/- macrophage HDLs responses are similar to wildtypes, i.e. excluding the IKK2-dependent canonical as well as the NIK-dependent non-canonical pathway. The pro-inflammatory activity of HDLs in macrophages was not attributable to ABCA1, ABCG1, SR-BI or CD36, established HDLs receptors, as HDLs show equivalent effects in macrophages from the respective knockout mice. Nevertheless, pre-treatment with β-methyl cyclodextrin abrogated the HDLs response, indicating that the pro-inflammatory effects are mediated by cholesterol depletion from macrophages. Although HDLs have been shown to exert anti-inflammatory functions in various cell types, our data point to pro-inflammatory effects of HDLs on macrophages in vitro and in vivo. Such detrimental effects on macrophages might limit the therapeutic potential of HDLs.
Can myocardial contrast echocardiography predict cardiac events in the patients with acute chest pain?
Authors: Pil-Ki Min, Hyun-Joo Kim, Jeong-Ah Ahn, Jae Hun Jung, Young-Sup Byun, Geu-ru Hong, Seok-Min Kang, Donghoon Choi, Se-Joong Rim, Yangsoo Jang, Namsik Chung
Journal: Journal of the American College of Cardiology (2003)
Sustained Inhibition of ε Protein Kinase C Inhibits Vascular Restenosis After Balloon Injury and Stenting
Authors: Tobias Deuse, Tomoyoshi Koyanagi, Reinhold G. Erben, Xiaoqin Hua, Joachim Velden, Fumiaki Ikeno, Hermann Reichenspurner, Robert C. Robbins, Daria Mochly-Rosen, Sonja Schrepfer
Journal: Circulation (2010)

ε protein kinase C (εPKC) is involved in vascular smooth muscle cell (VSMC) activation, but little is known about its function in vascular pathology. We aimed at assessing the role of εPKC in the development of restenosis.Rat models of aortic balloon injury with or without subsequent stenting were used. Rats were treated with the selective ψεPKC activator ε receptor for activated protein kinase C (ψεRACK), the selective εPKC inhibitor εV1-2, or saline. Both down-stream cascades of the platelet-derived growth factor receptor via extracellular signal-regulated kinase and Akt, respectively, were evaluated in vivo and in VSMC cultures. Intimal hyperplasia with luminal obliteration developed in saline-treated balloon-injured rat aortas (20.3±8.0%), and ψεRACK significantly promoted neointima development (32.4±4.9%, P=0.033), whereas εV1-2 significantly inhibited luminal narrowing (9.2±4.3%, P=0.039). εPKC inhibition led to significantly reduced VSMC extracellular signal-regulated kinase phosphorylation in vivo, whereas Akt phosphorylation was not markedly affected. Neointimal proliferation in vivo and platelet-derived growth factor-induced VSMC proliferation/migration in vitro were significantly inhibited by εV1-2. The inhibition of the platelet-derived growth factor pathway was mediated by inhibiting down-stream extracellular signal-regulated kinase and Akt phosphorylation. In vitro, εV1-2 showed inhibitory properties on endothelial cell proliferation, but that did not prevent reendothelialization in vivo. εV1-2 showed proapoptotic effects on VSMC in vitro. After stent implantation, luminal restenosis (quantified by optical coherence tomography imaging) was significantly reduced with εV1-2 (8.0±2.0%) compared with saline (20.2±9.8%, P=0.028).εPKC seems to be centrally involved in the development of neointimal hyperplasia. We suggest that εPKC inhibition may be mediated via inhibition of extracellular signal-regulated kinase and Akt activation. εPKC modulation may become a new therapeutic target against vascular restenosis.
DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia
Authors: Y Oshima, M Ueda, Y Yamashita, Y L Choi, J Ota, S Ueno, R Ohki, K Koinuma, T Wada, K Ozawa, A Fujimura, H Mano
Journal: Leukemia (2003)
Occupational skin diseases in Northern Bavaria between 1990 and 1999: a population-based study
Authors: H. Dickel, O. Kuss, C.R. Blesius, A. Schmidt, T.L. Diepgen
Journal: British Journal of Dermatology (2001)

Occupational skin diseases (OSDs) account for a large portion of occupational diseases in Europe, but population-based epidemiological studies are missing.We analysed the initial reports of OSDs in our register of OSDs in Northern Bavaria (BKH-N).A total of 5285 cases were assessed prospectively and registered from 1990 to 1999. As the German Federal Employment Office provides specific occupational data in relation to the total employed population of Northern Bavaria, it was possible to conduct a population-based study that investigated the trend in incidence rates between two study periods (1990-92 and 1993-99) in 24 different occupational groups.A total of 3097 cases of OSD (median age 25 years) were recorded in the 24 occupational groups. There was a significant decline (P < 0.001) in the overall incidence rate of OSD with 10.7 cases per 10,000 workers per year for the first study period and 4.9 cases per 10,000 workers per year for the second study period. This general trend in incidence rates was also significant for hairdressers and barbers, bakers, health-care workers, cooks and metal processors.The BKH-N provides national data based on the notification of OSDs in Germany. The results demonstrate the rank of occupations hazardous for the skin and are helpful for defining target groups for prevention.