tbuckley/cabot-search huggingface dataset:
Tumor B7-H1 Is Associated with Poor Prognosis in Renal Cell Carcinoma Patients with Long-term Follow-up
Authors: R. Houston Thompson, Susan M. Kuntz, Bradley C. Leibovich, Haidong Dong, Christine M. Lohse, W. Scott Webster, Shomik Sengupta, Igor Frank, Alexander S. Parker, Horst Zincke, Michael L. Blute, Thomas J. Sebo, John C. Cheville, Eugene D. Kwon
Journal: Cancer Research (2006)

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor.
Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction
Authors: So Hun Kim, Soo Hyun Kim, Minah Choi, Yongho Lee, Young Ook Kim, Duck Sun Ahn, Young Ho Kim, Eun Seok Kang, Eun Jig Lee, Mankil Jung, Jin Won Cho, Darren R. Williams, Hyun Chul Lee
Journal: Cardiovascular Research (2010)

We have investigated the effects of magnesium lithospermate B (MLB), the active compound of the Oriental herbal remedy, Salvia miltiorrhizae, on endothelial dysfunction associated with diabetes mellitus using cultured endothelial cells and an animal model of type 2 diabetes mellitus. The effect of MLB on vasodilatory function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was assessed. MLB treatment for 20 weeks starting at 12 weeks attenuated the decrease in endothelium-dependent vasodilation in OLETF rats. MLB treatment also increased serum nitrite level and reduced serum advanced glycation end products concentration. The effect of MLB was greater than an equivalent dose of α-lipoic acid (αLA), a popular antioxidant treatment. MLB rescued the inhibition of endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation in endothelial cells cultured in hyperglycaemia. This effect was dependent on Akt phosphorylation and associated with decreased O-linked N-acetylglucosamine protein modification of eNOS. MLB also increased nuclear factor erythroid 2-related factor-2 (Nrf-2) activation in a phosphoinositide 3-kinase/Akt pathway dependent manner. MLB treatment induced the expression of the Nrf-2-regulated antioxidant enzyme, heme oxygenase-1. The antioxidant αLA could not produce this effect. Moreover, MLB decreased oxidative stress and endothelial cell apoptosis caused by hyperglycaemia. MLB is a naturally occurring, new generation antioxidant that activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. The relative strong performance of MLB makes it an ideal candidate for further, expanded trials as a new generation of antioxidant to treat diabetes-related complications.
Mixed Form Lymphatic Malformation of the Foot Simulating Acute Soft-Tissue Lesion on 3-Phase Bone Scintigraphy
Authors: Serdar N. Haskok, Orhan Konez
Journal: Clinical Nuclear Medicine (2004)

A 15-year-old girl who presented with a congenital masslike soft-tissue lesion involving the second and third toes of the left foot was evaluated with various imaging modalities. Tc-99m methylene diphosphonate (MDP) 3-phase bone imaging was performed for further assessment of the lesion and to evaluate the underlying osseous structures, which showed increased tracer uptake on the first 2 phases. A mixed-form lymphatic malformation (LM) was diagnosed based on the typical clinical history, physical examination, and imaging findings. Despite the rarity of this condition, this report concludes that soft-tissue LM should be considered in the differential diagnosis when increased focal blood flow and soft-tissue uptake are seen on 3-phase bone scintigraphy.
A RESEARCH UPON ANÆSTHESIA
Authors: H. C. Wood, Wm. S. Carter
Journal: The Journal of Experimental Medicine (1897)

The conclusions which have been reached by the series of experiments recorded in the present memoir are: First. Lowered arterial pressure has a comparatively feeble effect upon the respiration, but when the pressure falls sufficiently, respiratory depression does occur. Second. Even excessive lowering of blood pressure primarily stimulates the vaso-motor centre, the sensibility of the centre being evidently necessary to the automatic regulation of the circulation. Third. The circulation recovers itself more slowly after profound etherization than after a like chloroform narcosis. Fourth. It is possible for ether as well as chloroform to produce death some hours after the cessation of its administration, at a time when the cerebrum has long freed itself from distinct evidences of the narcotic, so that consciousness and intellectual action have been restored. In applying these conclusions to the subject of practical anæsthesia it is evident that the depression of the circulation produced by chloroform has effect upon the respiratory centres only when the pressure has fallen very low, and whilst it may be a factor in the production of respiratory failure during chloroformization, the failure must be chiefly due to the direct influence exercised by the drug upon the respiratory centres. Clinical experience shows that nausea and general depression are more pronounced after the use of ether than after the use of chloroform, a difference which is strongly insisted upon by the advocates of chloroform as an important agent in favor of that anæsthetic. Our research confirms clinical observation, and experimentally shows that the depression of the circulation produced by ether is more permanent than that caused by chloroform; the reason probably being the large amount of ether which is necessary to produce profound narcosis, with lowering of the arterial pressure; an amount so large that it can neither be burned up in the system nor yet eliminated in the time which would be necessary for the much smaller amount of chloroform to be gotten rid of after chloroformization.
On the possible role of long chain fatty acylcarnitine accumulation in producing functional and calcium permeability changes in membranes during myocardial ischaemia
Authors: J. M J LAMERS, J. T D. JONGE-STINIS, P. D VERDOUW, W. C HULSMANN
Journal: Cardiovascular Research (1987)

Journal Article On the possible role of long chain fatty acylcarnitine accumulation in producing functional and calcium permeability changes in membranes during myocardial ischaemia Get access JOS M J LAMERS, JOS M J LAMERS ** From the Department of Biochemistry I, Erasmus University Rotterdam, Rotterdam, The Netherlands Address for correspondence and reprints: Dr Jos M J Lamers, Department of Biochemistry I, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHANNA T DE JONGE-STINIS, JOHANNA T DE JONGE-STINIS ** From the Department of Biochemistry I, Erasmus University Rotterdam, Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar PIETER D VERDOUW, PIETER D VERDOUW † From the Thoraxcentre, School of Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar WILLEM C HÜLSMANN WILLEM C HÜLSMANN ** From the Department of Biochemistry I, Erasmus University Rotterdam, Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 5, May 1987, Pages 313–322, https://doi.org/10.1093/cvr/21.5.313 Published: 01 May 1987 Article history Received: 19 June 1986 Accepted: 15 October 1986 Published: 01 May 1987
Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes
Authors: Francine V. van Venrooij, Marcel A. van de Ree, Michiel L. Bots, Ronald P. Stolk, Menno V. Huisman, J. D. Banga
Journal: Diabetes Care (2002)

OBJECTIVE—Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might be an effective method to improve endothelial function in these patients. RESEARCH DESIGN AND METHODS—A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks’ administration of atorvastatin 10 mg and 80 mg on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease. RESULTS—Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilatation was found (P &amp;gt; 0.8). CONCLUSIONS—We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction.
Bisphosphonates associated osteonecrosis of the jaw: A long‐term follow‐up of a series of 35 cases observed by GISL and evaluation of its frequency over time
Authors: Samantha Pozzi, Raffaella Marcheselli, Simona Falorio, Luciano Masini, Caterina Stelitano, Antonietta Falcone, Giovanni Quarta, Luisa Ponchio, Vincenzo Pitini, Stefano Luminari, Luca Baldini
Journal: American Journal of Hematology (2009)

d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Safety and effectiveness of nurse telephone consultation in out of hours primary care
Authors: V. Tanna, K. Blackmore, L. Dodd, S. Twist, S. George, V. Lattimer
Journal: BMJ (1999)

Editor—Lattimer et al report a randomised controlled trial to show the safety and effectiveness of nurse telephone consultations in out of hours primary care.1 I accept that the results showed a reduced workload for general practitioners from the nurse intervention, probably at an increased cost. For methodological reasons, however, I am less certain whether the results show safety.

Lattimer et al report that during intervention periods, 49.8% of the calls could be managed by the nurse alone without referral to a doctor. This implies that 50.2% of the calls were assessed twice: once by an experienced and specially trained nurse using a systematic assessment with the aid of decision support software and then by the general practitioner in attendance. I would expect that the improved diagnosis and management in this subgroup would lead to much better clinical outcomes than in the control group, which had only one assessment by the general practitioner. This improved outcome could mask the potentially poorer outcomes in the 49.8% of calls handled by the nurse alone. By combining the outcomes for essentially two interventions (nurse alone and nurse and general practitioner) into a single intervention group, the issue has been clouded. I therefore question the conclusion that nurse telephone consultation is at least as safe as existing out of hours care.

To convince a sceptic of the safety of nurse telephone consultations, the outcomes for patients managed by the nurse alone should be compared with the outcomes for matched patients in the control group. I wonder whether the authors can extract this information from their data. It may be that the trial would have to run for longer than one year to fulfil sample size criteria for such a comparison.
Peripheral Nervous System Function and Organophosphate Pesticide Use among Licensed Pesticide Applicators in the Agricultural Health Study
Authors: Sarah E. Starks, Jane A. Hoppin, Freya Kamel, Charles F. Lynch, Michael P. Jones, Michael C. Alavanja, Dale P. Sandler, Fred Gerr
Journal: Environmental Health Perspectives (2012)

Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function.Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS).Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates.Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold.Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators.
Expert group warns radiotherapy is still underused in England
Authors: S. Mayor
Journal: BMJ (2011)

Only about two thirds of cancer patients in England who would benefit from radiotherapy currently receive it, warns an expert group that is recommending improved awareness and training about the latest targeted radiotherapy techniques in cancer treatment.

Modelling suggests that just over half (52%) of cancer patients could benefit from radiotherapy, but only 37% receive it, Mike Richards, national clinical director for cancer, told the meeting. “Lack of awareness among some doctors of the efficacy and the low rate of side effects with some of the latest techniques for delivering radiotherapy may explain the underuse of this treatment option for cancer.

“We have introduced measures to deal with lack of staffing and resources in radiotherapy and improved previously long waiting times. The next step is improving commissioning of radiotherapy so that patients who …
Association between stress and glycemic control in adults with type 1 (insulin-dependent) diabetes.
Authors: C E Lloyd, P H Dyer, R J Lancashire, T Harris, J E Daniels, A H Barnett
Journal: Diabetes Care (1999)

OBJECTIVE: To examine the relationship between stressful life events and alterations in glycemic control in adults with diabetes. RESEARCH DESIGN AND METHODS: The occurrence of stressful experiences was recorded using the life Events and Difficulties Schedule of Brown and Harris in 55 adults with type 1 diabetes. The two most recent measures of glycemic control (HbA1c) were obtained from medical records, with poor glycemic control defined by the sample median (&amp;gt; or =7.7%). RESULTS: Subjects whose control deteriorated over time or who remained in poor glycemic control were significantly more likely to report severe personal stressors (SPS) in the month before HbA1c measurement, compared with subjects whose control remained fair or whose control improved (43 and 25% vs. 7 and 0%; P = 0.000). Subjects whose control remained fair or whose control improved were significantly more likely to report only positive life events during the same time period (80 and 11% vs. 0 and 0%, respectively; P = 0.000). Multiple regression analysis demonstrated that SPS, sex, and lack of further education were all significantly associated with either remaining in poor control or deterioration of control. CONCLUSIONS: The study has shown that recent severe stressors are associated with poorer glycemic control. Positive life events were associated with fair or improved glycemic control. This study has its limitations, and future studies should be prospective in design. While it is not always possible to avoid stress, learning to recognize and cope with stressors may help individuals with diabetes maintain good glycemic control and improve overall quality of life.
Screening for cancer with computed tomography
Authors: S. J Swensen
Journal: BMJ (2003)

Whole body screening with computed tomography is the focus of a major advertising campaign in the United States. Enticing testimonials on billboards and radio spots urge the public to use this technology, implying that there is much to gain and little to lose. How should primary care doctors advise their patients?

In one sense screening with computed tomography has much to offer. As part of a study conducted by the National Institutes of Health, our centre has used computed tomography to screen for lung cancer for the past four years and has identified 56 lung cancers. Fully 62% of the non-small cell cancers were stage IA.1 In the absence of screening, only 15-20% of lung cancers present at stage IA. Five year survival for stage I lung cancers, which is about 60-70%, is higher than for cancers diagnosed at more advanced stages. There is little doubt that computed tomography is more sensitive than chest x ray in detecting small, early stage lung cancers. We found two cancers measuring only 3 mm in diameter.

Recognising that we found 56 patients with lung cancer, one could ask why …
More DNA support for a Cetacea/Hippopotamidae clade: the blood-clotting protein gene gamma-fibrinogen
Authors: J. Gatesy
Journal: Molecular Biology and Evolution (1997)

Recent phylogenetic analyses of DNA sequences suggest that cetaceans (whales) and hippopotamid artiodactyls (hippos) are extant sister taxa. Consequently, the shared aquatic specializations of these taxa may be synapomorphies. This molecular view is contradicted by paleontological data that overwhelmingly support a monophyletic Artiodactyla (even-toed ungulates) and a close relationship between Cetacea and extinct mesonychian ungulates. According to the fossil evidence, molecular, behavioral, and anatomical resemblances between hippos and whales are interpreted as convergences or primitive retentions. In this report, competing interpretations of whale origins are tested through phylogenetic analyses of the blood-clotting protein gene gamma-fibrinogen from cetaceans, artiodactyls, perissodactyls (odd-toed ungulates), and carnivores (cats, dogs, and kin). In combination with published DNA sequences, the gamma-fibrinogen data unambiguously support a hippo/whale clade and are inconsistent with the paleontological perspective. If the phylogeny favored by fossil evidence is accepted, the convergence at the DNA level between Cetacea and Hippopotamidae is remarkable in its distribution across three genetic loci: gamma-fibrinogen, the linked milk casein genes, and mitochondrial cytochrome b.
Cosmetic laser treatment is dangerously unregulated, warn experts
Authors: J. Wise
Journal: BMJ (2012)

Experts have called for cosmetic laser treatment to be regulated, warning that its misuse can result in skin burns, blistering, scarring, and permanent blindness.

Laser and intense pulse light cosmetic treatments are becoming increasingly popular for the removal of hair, tattoos, and birthmarks as well as for skin “rejuvenation” or “resurfacing.” These treatments are offered at an estimated 10 000 beauty salons and clinics in England and there is no requirement that the practitioner is trained or registered.

Experts from the Society for Radiological Protection expressed their concerns at a press conference in London on 9 May ahead of the International Radiation Protection Association Congress in Glasgow later this month.

“Lasers, by their nature, are dangerous pieces of equipment,” warned Harry Moseley, consultant clinical scientist and head of a dermatological laser clinic at Ninewells Hospital in Dundee, which treats both NHS and private patients. He said he knew of many cases where patients had been …
SC-31 * RATIONAL DESIGN OF A PI3-KINASE/mTOR INHIBITOR CYTOTOXIC TO BRAIN CANCER STEM CELLS UNDER HYPOXIA
Authors: N. Vad, S. Jagannathan, K. Sumita, M. Abdel-Malek, J. Driscoll
Journal: Neuro-Oncology (2014)

Small molecules that modulate cancer stem cell (CSC) fate and function offer therapeutic potential to improve patient outcome. Malignant gliomas are highly aggressive primary brain tumors with few treatment options and an invariably fatal outcome. High-throughput screening and structure-guided design identified a novel, dual phosphatidylinositol-3-kinase (PI3K)/mammaliam target of rapamycin (mTOR) inhibitor that potently induced apoptosis in glioma cells and glioma patient-derived CSCs. The compound, designated DT61, inhibited PI3K, mTORC1 and mTORC2 kinase activities at nanomolar concentrations in a dose-dependent manner. DT61 dramatically reduced the level of the PI3-K α and β isoforms and led to a reduction in the site-specific phosphorylation and activity of the pro-survival serine-threonine kinase Akt/Protein Kinase B (PKB). DT61 inhibition of PI3K activity prevented the inactivation of glycogen synthase kinase (GSK-3beta) to enhance site-specific phosphorylation and proteasomal degradation of the c-myc oncoprotein that drives gliomagenesis. The apoptotic effect of DT61 on CSCs was synergistically enhanced when combined with radiation treatment, a standard-of-care modality for glioma treatment. Taken together, the results demonstrate that DT61 is a novel, highly effective dual PI3K/mTOR inhibitor that is cytotoxic to brain CSC under normoxia and hypoxia with potential benefit for glioma patients.
Malaria Vaccine Trials — Beyond Efficacy End Points
Authors: Johanna P. Daily
Journal: New England Journal of Medicine (2012)

Plasmodium falciparum infection, malaria, continues to cause more than 1 million childhood deaths each year.1 In addition, millions of nonlethal infections affect communities on an economic basis and inhibit children from reaching their full developmental potential.2 The creation of an effective vaccine has been a long-sought, elusive goal.The first results of the phase 3 trial of the candidate malaria vaccine RTS,S/AS01, which is being conducted in seven African countries, were reported for children 5 to 17 months of age at enrollment, with a vaccine efficacy of 56% against all clinical malaria infections and 47% against severe malaria during a . . .