tbuckley/cabot-search huggingface dataset:
Sentinel lymph node biopsy in malignant melanoma
Authors: J Meirion Thomas
Journal: BMJ (2008)

<h3>Objective</h3> Metabolic reprogramming of tumour cells that allows for adaptation to their local environment is a hallmark of cancer. Interestingly, obesity-driven and non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) mouse models commonly exhibit strong steatosis in tumour cells as seen in human steatohepatitic HCC (SH-HCC), which may reflect a characteristic metabolic alteration. <h3>Design</h3> Non-tumour and HCC tissues obtained from diethylnitrosamine-injected mice fed either a normal or a high-fat diet (HFD) were subjected to comprehensive metabolome analysis, and the significance of obesity-mediated metabolic alteration in hepatocarcinogenesis was evaluated. <h3>Results</h3> The extensive accumulation of acylcarnitine species was seen in HCC tissues and in the serum of HFD-fed mice. A similar increase was found in the serum of patients with NASH-HCC. The accumulation of acylcarnitine could be attributed to the downregulation of carnitine palmitoyltransferase 2 (CPT2), which was also seen in human SH-HCC. CPT2 downregulation induced the suppression of fatty acid β-oxidation, which would account for the steatotic changes in HCC. CPT2 knockdown in HCC cells resulted in their resistance to lipotoxicity by inhibiting the Src-mediated JNK activation. Additionally, oleoylcarnitine enhanced sphere formation by HCC cells via STAT3 activation, suggesting that acylcarnitine accumulation was a surrogate marker of CPT2 downregulation and directly contributed to hepatocarcinogenesis. HFD feeding and carnitine supplementation synergistically enhanced HCC development accompanied by acylcarnitine accumulation in vivo. <h3>Conclusion</h3> In obesity-driven and NASH-driven HCC, metabolic reprogramming mediated by the downregulation of CPT2 enables HCC cells to escape lipotoxicity and promotes hepatocarcinogenesis.
Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer
Authors: Sunita K. Patel, Andrew L. Wong, F. Lennie Wong, Elizabeth Crabb Breen, Arti Hurria, Mackenzie Smith, Christine Kinjo, I. Benjamin Paz, Laura Kruper, George Somlo, Joanne E. Mortimer, Melanie R. Palomares, Michael R. Irwin, Smita Bhatia
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Neurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by pro-inflammatory cytokines.
Pancreatitis during therapy of acute myeloid leukemia: Cytarabine related?
Authors: L.H. McGrail, L.H. Sehn, R.B. Weiss, M.R. Robson, J.H. Antin, J.C. Byrd
Journal: Annals of Oncology (1999)

Background: Acute pancreatitis in acute myeloid leukemia (AML) has been rarely associated with cytarabine therapy.This report attempts to characterize this toxicity.Patients and methods: Criteria for pancreatitis was prospectively defined.Seven patients with pancreatitis were identified from an AML database and a clinical study at two tertiary care centers (n = 134).Their records were retrospectively reviewed.Results: Seven patients with pancreatitis complicating AML therapy were identified.Median age was 36 (range 25-73) years.Median amylase was 184 (range 77-552) U/l and median lipase was 1026 (range 630-6087) U/l.The patients had received high dose bolus cytarabine (2 g/m 2 i.v.bolus every 12 hours; n -2), and continuous infusion cytarabine followed by high-dose cytarabine (100 mg/m 2 i.v.CI days 1-7 then 2 g/m 2 i.v.bolus every 12 hours days 8-10; n = 2), or standard dose continuous infusion cytarabine (200 mg/m 2 /d; n -3) prior to developing pancreatitis.Pancreatitis occurred at a median of 10 days following day one of cytarabine administration with resolution at a median of 11 days after initial diagnosis.Six patients did not suffer major complications.One patient died of causes unrelated to pancreatitis.Five of six patients was rechallenged and all remained free of pancreatitis.One patient subsequently did develop pancreatitis on a later rechallenge.Conclusions: Pancreatitis in the setting of AML therapy may be an infrequent and self-limited toxicity of cytarabine.A schedule dependent toxicity with cytarabine was not identified.
COPE guidelines on good publication practice
Authors: M. DOHERTY
Journal: Annals of the Rheumatic Diseases (2000)

The Committee on Publication Ethics (COPE) was founded in 1997 by a group of UK medical editors who wished to discuss specific examples of possible research and publication misconduct that they were currently facing. A few, such as the editors of the Lancet and BMJ , were full time professional editors with a large publishing staff and ready access to expert advice. Most, however, were more isolated part time editors who had received no formal training in publication issues. Additional committee members provided expertise on medical ethics, law, and the practical consequences of actions such as “whistle-blowing”. The discussions of cases by COPE, published regularly in anonymised form,1 2 focus on the practicalities of what should and what could be done in each specific case. These case discussions have proved useful not only to guide appropriate action in …
Does Ischemic Preconditioning in the Human Involve Protein Kinase C and the ATP-Dependent K <sup>+</sup> Channel?
Authors: M. E. Speechly-Dick, G. J. Grover, D. M. Yellon
Journal: Circulation Research (1995)

Protein kinase C (PKC) and the ATP-dependent K+ channel (KATP channel) have been implicated in the mechanism of ischemic preconditioning in animal models. This study investigated the role of KATP channels and PKC in preconditioning in human myocardium and whether KATP channels are activated via a PKC-dependent pathway. Right atrial trabeculae were superfused with Tyrode's solution and paced at 1 Hz. After stabilization, muscles underwent one of nine different protocols, followed by simulated ischemia (SI) consisting of 90 minutes of hypoxic substrate-free superfusion paced at 3 Hz and then by 120 minutes of reperfusion. Preconditioning consisted of 3 minutes of SI and 7 minutes of reperfusion. The experimental end point was recovery of contractile function after SI, presented here as percentage recovery (%Rec) of baseline function. %Rec was significantly improved by preconditioning by the KATP channel opener cromakalim (CK), and by the PKC activator 1,2-dioctanoyl-sn-glycerol (DOG) compared with nonpreconditioned controls when these treatments were given before the SI insult (control group, 29.5 +/- 3.6%; preconditioned group, 63.5 +/- 5.4%, CK-treated group, 52.9 +/- 3.1%; and DOG-treated group, 48.0 +/- 3.5%; P < .01). The effects of CK could be blocked by the KATP channel blocker glibenclamide (%Rec, 17.8 +/- 3.5%). Preconditioning could be blocked by the PKC antagonist chelerythrine (%Rec, 24.1 +/- 5.0%) and the KATP blocker glibenclamide (%Rec, 24.8 +/- 3.1%). The effects of DOG could also be blocked by glibenclamide (%Rec, 23.1 +/- 2.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Clinics in neurology and neurosurgery of sport: cervical disc prolapse
Authors: G Davis, P Hamlyn, W R Sears, P McCrory
Journal: British Journal of Sports Medicine (2008)

A cervical intervertebral disc can prolapse (hernia or rupture) asymptomatically or may produce neck pain, nerve root compression (radiculopathy) or spinal cord compression (myelopathy). Surgery is indicated in cases of cervical myelopathy. In cases of symptomatic cervical radiculopathy, surgery is indicated in cases that fail to respond to conservative treatment. Surgical approaches to the cervical spine are usually anterior or posterior. Currently, anterior cervical discectomy is the most common procedure used. This may be performed alone or with the addition of fusion (insertion of a bone graft) and with or without instrumentation (an intervertebral prosthesis or use of plates or screws). An alternative to fusion (arthrodesis) is a disc replacement (arthroplasty). There is extensive debate among spinal surgeons as to the most appropriate technique, and as the literature lacks absolute clarity regarding the superiority of one technique over another, most spinal surgeons use the technique that works well in their hands.

A 25-year-old professional soccer player is involved in a motor vehicle crash, sustaining an acute C6–7 disc prolapse with radiculopathy (figs 1 and 2). He undergoes C6–7 anterior cervical discectomy and fusion. Postoperatively he is neurologically intact. Three months have now passed and you are asked to provide your expert opinion. What recommendations do you make, based on the following considerations?

1.  Can the patient return to play?

2.  If so, when? Do you place any restrictions on him and is there any further follow-up that you require?

3.  If you determine that he may not return to play, please explain your reasons for this) If you review him 12 months after surgery and plain x-ray of the cervical spine shows solid fusion, with stable flexion extension x-rays of the cervical spine, would this alter your decision? Are there any other factors that would alter your decision?



Figure 1 
Sagittal T2-weighted MRI scan of …
Effects of vitamins on chromium(VI)-induced damage.
Authors: M Sugiyama
Journal: Environmental Health Perspectives (1991)

The effects of vitamin E and vitamin B2 on DNA damage and cellular reduction of chromium(VI) were investigated using Chinese hamster V-79 cells. Pretreatment with alpha-tocopherol succinate (vitamin E) resulted in a decrease of DNA single-strand breaks produced by Na2CrO4, while similar treatment with riboflavin (vitamin B2) enhanced levels of DNA breaks. In contrast, levels of DNA-protein crosslinks induced by Na2CrO4 were unaffected by these vitamins. Electron spin resonance (ESR) studies showed that incubation of cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complexes, and cellular pretreatment with vitamin E reduced the level of the chromium(V) complex, whereas pretreatment with vitamin B2 enhanced the level of this intermediate. However, the levels of chromium(III) were unchanged by these vitamins. The uptake of chromate was not affected by vitamin E or vitamin B2, nor were the levels of glutathione or glutathione reductase activity, which are both capable of reducing chromate. ESR studies demonstrated that a chromium(V) species was formed by the reaction of Na2CrO4 with vitamin B2 and that vitamin B2 enhanced the formation of hydroxyl radicals during the reaction of Na2CrO4 and hydrogen peroxide. Treatment cells with Na2CrO4 resulted in a decrease of glutathione reductase activity, and pretreatment with vitamin E restored the enzyme activity suppressed by this metal. However, pretreatment with vitamin B2 enhanced the inhibition of this enzyme by Na2CrO4. Using a colony-forming assay, pretreatment with vitamin E dramatically decreased the cytotoxicity of Na2CrO4, while pretreatment with vitamin B2 was found to result in only a decrease of cell lethality of this metal.(ABSTRACT TRUNCATED AT 250 WORDS)
Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: prospective two centre study
Authors: Jorge A Cepeda, Tony Whitehouse, Ben Cooper, Janeane Hails, Karen Jones, Felicia Kwaku, Lee Taylor, Samantha Hayman, Barry Cookson, Steve Shaw, Chris Kibbler, Mervyn Singer, Geoffrey Bellingan, A Peter R Wilson
Journal: The Lancet (2005)
Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations
Authors: I. Garcia-Olivé, E. Monsó, F. Andreo, J. Sanz-Santos, M. Taron, M. A. Molina-Vila, M. Llatjós, E. Castellà, T. Moran, J. Bertran-Alamillo, C. Mayo-de-las-Casas, C. Queralt, R. Rosell
Journal: European Respiratory Journal (2009)

The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of &gt;5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.
Morphometry of canine coronary arteries, arterioles, and capillaries during hypertension and left ventricular hypertrophy.
Authors: R J Tomanek, P J Palmer, G L Peiffer, K L Schreiber, C L Eastham, M L Marcus
Journal: Circulation Research (1986)

The mechanisms responsible for the increase in minimal coronary vascular resistance per unit mass of myocardium in animals with chronic hypertension and left ventricular hypertrophy remain unidentified. Because increases in wall thickness of resistance vessels in some vascular beds in response to hypertension may decrease luminal diameter, we hypothesized that similar changes may occur in the coronary vasculature. To test this hypothesis, we performed hemodynamic and morphometric studies on eight dogs with renovascular hypertension (one kidney, one clip) of 6 weeks' duration, and in six normotensive dogs. Hypertension evoked a 27% increase in left ventricular mass and was associated with a 67% increase in left ventricular minimal coronary vascular resistance per 100 g calculated from coronary perfusion measured with microspheres during adenosine infusion. The vasculature was fixed via perfusion of glutaraldehyde and tissue samples from the left ventricle were embedded in Epon. Wall:lumen ratios, determined by light microscopy, of coronary arteries and arterioles were similar in hypertensive and normotensive dogs. Lumen diameters of large epicardial arteries (greater than 640 microns) of hypertensive dogs increased significantly so that wall:lumen ratios were normal despite an increased medial thickness. Ultrastructural analysis, however, showed an enhancement of the relative extracellular compartment of the tunica media of large coronary arteries of hypertensive dogs: 36.4 +/- 3.4% vs. 26.5 +/- 1.6% (mean +/- SEM). Capillary numerical density and surface area (surface area:tissue volume) were significantly lower in the endomyocardium, while capillary volume density (volume:tissue volume) was lower in the midmyocardium and endomyocardium of hypertensive dogs compared to normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)
Infection of Peritoneum during Dialysis
Authors: E. N. Wardle
Journal: BMJ (1973)

The hypothesis that the accumulation of uroporphyrin, characteristic of uroporphyria, arises at least in part from oxidation of uroporphyrinogen and the molecular basis for the potentiation of the disorder by iron have been investigated. The iron chelates of ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid were very active at promoting the hydrogen peroxide-dependent oxidation of porphyrinogens, and a similar role of iron was found for the NADPH-dependent oxidation of porphyrinogens by liver microsomes in vitro. In contrast, neither the iron chelate of desferrioxamine (DES) nor ferritin iron possessed prooxidant activity, but the latter could be mobilized in an active form by incubation with EDTA. Iron was also found to promote further modification of the porphyrin pigment, leading to marked loss of its Soret absorbance. This latter effect, which could also be inhibited by DES, suggested further oxidative conversion of the accumulating uroporphyrin, but further work is necessary to establish the relevance of this (or similar) reaction to the inhibitor of uroporphyrinogen decarboxylase which has recently been reported. These results suggest a possible mechanism for the exacerbation of uroporphyria by excess iron and also for its marked improvement when the iron stores are diminished, for example, by DES treatment.
Three-Dimensional and Molecular Analysis of the Venous Pole of the Developing Human Heart
Authors: Aleksander Sizarov, Robert H. Anderson, Vincent M. Christoffels, Antoon F.M. Moorman
Journal: Circulation (2010)

Various congenital malformations and many abnormal rhythms originate from the venous pole of the heart. Because of rapid changes during morphogenesis, lack of molecular and lineage data, and difficulties in presenting complex morphogenetic changes in the developing heart in a clear fashion, the development of this region in human has been difficult to grasp.To gain insight into the development of the different types of myocardium forming the venous pole of the human heart, we performed an immunohistochemical and 3-dimensional analysis of serial sections of human embryos ranging from 22 through 40 days of development. Three-dimensional models were prepared in a novel interactive portable format providing crucial spatial information and facilitating interpretation. As in the mouse, the systemic venous myocardium expresses the transcription factor TBX18, whereas the pulmonary venous myocardium expresses NKX2-5. In contrast to the mouse, a systemic venous sinus is identified upstream from the atrial chambers, albeit initially with nonmyocardial walls. From the outset, as in the mouse, the pulmonary vein empties to a chamber with atrial, rather than systemic venous, characteristics. Compared with the mouse, the vestibular spine is a more prominent structure.The similarities in gene expression in the distinctive types of myocardium surrounding the systemic and pulmonary venous tributaries in man and mouse permit extrapolation of the conclusions drawn from transgenic and lineage studies in the mouse to the human, showing that the systemic and pulmonary venous myocardial sleeves are derived from distinct developmental lineages.
Mechanism of luminal enlargement by optimal atherectomy — IVUS insights from the OARS study
Authors: Donald S. Baim, Charles A. Simonton, Jeffrey J. Popma, Tomaki Hinohara, Robert M. Bersin, Tia DeFeo, Kenneth M. Kent, Paul G. Yock, Richard E. Kuntz
Journal: Journal of the American College of Cardiology (1996)
Structure-Based Assessment of Missense Mutations in Human BRCA1
Authors: Nebojsa Mirkovic, Marc A. Marti-Renom, Barbara L. Weber, Andrej Sali, Alvaro N. A. Monteiro
Journal: Cancer Research (2004)

Abstract The BRCA1 gene from individuals at risk of breast and ovarian cancers can be screened for the presence of mutations. However, the cancer association of most alleles carrying missense mutations is unknown, thus creating significant problems for genetic counseling. To increase our ability to identify cancer-associated mutations in BRCA1, we set out to use the principles of protein three-dimensional structure as well as the correlation between the cancer-associated mutations and those that abolish transcriptional activation. Thirty-one of 37 missense mutations of known impact on the transcriptional activation function of BRCA1 are readily rationalized in structural terms. Loss-of-function mutations involve nonconservative changes in the core of the BRCA1 C-terminus (BRCT) fold or are localized in a groove that presumably forms a binding site involved in the transcriptional activation by BRCA1; mutations that do not abolish transcriptional activation are either conservative changes in the core or are on the surface outside of the putative binding site. Next, structure-based rules for predicting functional consequences of a given missense mutation were applied to 57 germ-line BRCA1 variants of unknown cancer association. Such a structure-based approach may be helpful in an integrated effort to identify mutations that predispose individuals to cancer.
Failure to change care provision will leave more UK trusts in financial difficulty, say MPs
Authors: A. O'Dowd
Journal: BMJ (2014)

The longer NHS trusts fail to change how they provide care, the more likely they will be to run into financial trouble, MPs have warned.

In a report published on 26 March by the parliamentary health select committee,1 MPs said that trusts were not changing their models of care quickly enough and were doomed to hit serious financial problems as a result.

The report followed the committee’s annual accountability hearing2 with Monitor, which regulates the health sector in England. The report recommended that Monitor should review its relationships with providers in primary care and the third sector because it had not yet developed a good enough …
Strain Dependency of Hormonally Activated C-Type RNA Tumor Virus Markers in Mice
Authors: A. K. Fowler, P. J. McConahey, A. Hellman
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Strain Dependency of Hormonally Activated C-Type RNA Tumor Virus Markers in Mice Get access A. K. Fowler, A. K. Fowler National Cancer Institute,4Bethesda, Maryland 20014; and Scripps Clinic and Research Foundation, La Jolla, California 92037 Search for other works by this author on: Oxford Academic PubMed Google Scholar P. J. McConahey, P. J. McConahey National Cancer Institute,4Bethesda, Maryland 20014; and Scripps Clinic and Research Foundation, La Jolla, California 92037 Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Hellman A. Hellman National Cancer Institute,4Bethesda, Maryland 20014; and Scripps Clinic and Research Foundation, La Jolla, California 92037 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 4, April 1973, Pages 1057–1059, https://doi.org/10.1093/jnci/50.4.1057 Published: 01 April 1973 Article history Received: 13 November 1972 Accepted: 22 January 1973 Published: 01 April 1973