tbuckley/cabot-search huggingface dataset:
Reply to: Hepatic microvascular dysfunction and endotoxemia in sepsis
Authors: Chantal A. Rivera, D. Neil Granger, Georg Singer
Journal: Journal of Hepatology (2008)

We thank Dr. Fujita [[1]Fujita T. Hepatic microvascular dysfunction and endotoxemia in sepsis.J Hepatol. 2008; 48: 676Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] for the constructive and insightful comments about our recent report [[2]Singer G. Houghton J. Rivera C.A. Anthoni C. Granger D.N. Role of LPS in the hepatic microvascular dysfunction elicited by cecal ligation and puncture in mice.J Hepatol. 2007; 47: 799-806Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar] and appreciate the opportunity to respond to the questions raised regarding: (1) the units used to express endotoxin concentrations detected in blood; and (2) the interpretation of our findings about the potential role of endotoxin in the hepatic microvascular responses to experimental sepsis. We regret the confusion that resulted from expressing endotoxin concentrations in terms of both EU/ml and pg/ml. Although we did not measure endotoxin activity per se, the concentrations of endotoxin in plasma were analyzed using a chromagenic limulus test and were estimated based on standards constructed with endotoxin serotype 055:B5. This serotype has an approximate activity of 1 EU = 100 pg/ml, based on the manufacturer’s suggestions. Thus, our data can easily be converted by simply multiplying the EU/ml values provided in Table 2 by a factor of 100. However, since endotoxin was undetectable following cecal ligation and puncture (CLP), this conversion would not affect the overall outcome of the study. Finally, we agree that rapid clearance of endotoxin may account for lowered endotoxin levels in the circulation of mice following CLP. Unlike the experiments wherein only one dose of endotoxin was injected, CLP likely induces the sustained release of endotoxin. As a result, large amounts of endotoxin should have been detected at any time point throughout the 6-h exposure, especially in the portal blood draining the gut. The absence of detectable endotoxin in blood does not, on its own, justify the conclusion that “our findings do not support a major role for LPS in the hepatic microvascular disturbances associated with polymicrobial sepsis”. This conclusion was based on a collective body of evidence that included the absence of enhanced mRNA expression for TLR-4 or the adaptor molecule MD-2 in the livers of septic mice, as well as our observation that the hepatic microcirculation of endotoxin-sensitive and -insensitive (TLR-4 deficient) mice responded in a nearly identical fashion to CLP, while the TLR-4 mutants were protected against exogenous endotoxin. We believe that these observations following CLP, coupled with the absence of detectable endotoxin in blood, warrant the conclusion drawn in our report. Additional work is needed to further address the importance of endotoxin and products from Gram-positive bacteria in liver pathology.
The energetics of myocardial stretch. Creatine kinase flux and oxygen consumption in the noncontracting rat heart.
Authors: J A Bittl, J S Ingwall
Journal: Circulation Research (1986)

Previous studies have suggested that flux through the creatine kinase reaction is coupled to cardiac performance and to the rate of adenosine triphosphate synthesis in the intact, beating heart. To define the effect of passive myocardial stretch on creatine kinase kinetics, we measured the rate constants and chemical fluxes for both directions of the creatine kinase reaction with the 31P-nuclear magnetic resonance technique of magnetization transfer in isolated, arrested rat hearts at four levels of left ventricular pressure and volume. Adenosine triphosphate synthesis was estimated from oxygen consumption measurements. As left ventricular pressure rose from 0 to 24 mm Hg and oxygen consumption increased by 20%, we observed a twofold increase in the rate constants and fluxes (mean +/- SD, n = 4-7) for the creatine kinase reaction. The forward rate constant increased from 0.33 +/- 0.03 to 0.80 +/- 0.08, and the reverse rate increased from 0.34 +/- 0.11 to 0.74 +/- 0.32/sec. The forward and reverse fluxes for the creatine kinase reaction increased from 12.0 +/- 3.4 to 26.5 +/- 5.8 and from 9.1 +/- 3.4 to 19.1 +/- 3.4 mumol/g dry weight per sec, respectively. At each level of left ventricular pressure, the forward and reverse rate constants were the same. However, as left ventricular pressure increased, the ratio of the forward to the apparent reverse fluxes for the creatine kinase reaction increased. The relationships between the rate constant or flux through the creatine kinase reaction vs. left ventricular pressure were linear. In addition to providing further support for the coupling between creatine kinase and mitochondrial adenosine triphosphate synthesis, these results suggest that flux through the creatine kinase reaction and adenosine triphosphate synthesis increases with myocardial stretch in the intact, noncontracting heart.
Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy
Authors: Zhao-Yang Wang, Qing-Feng Liu, Hua Wang, Jing Jin, Wei-Hu Wang, Shu-Lian Wang, Yong-Wen Song, Yue-Ping Liu, Hui Fang, Hua Ren, Run-Ye Wu, Bo Chen, Xi-Mei Zhang, Ning-Ning Lu, Li-Qiang Zhou, Ye-Xiong Li
Journal: Blood (2012)
Reoxygenation of Hypoxic Coronary Smooth Muscle Cells Amplifies Growth-Retarding Effects of Ionizing Irradiation
Authors: Amina Arab, Thorsten Grumann, Roland Guttenberger, Christoph Bode, Christoph Hehrlein
Journal: Circulation (2004)

Hypoxic human coronary smooth muscle cells (HCSMCs) are possible targets for brachytherapy to prevent restenosis after percutaneous transluminal coronary angiography. It is unclear whether growth kinetics and gene expression of these cells undergoing gamma-irradiation are changed by reoxygenation.Hypoxic (H) and hypoxia-reoxygenated (H-R) HCSMCs were irradiated with gamma-radiation at single doses of 4, 8, and 16 Gy using a 60Co-source. Vascular endothelial growth factor gene expression of HCSMCs was dramatically suppressed in H-R versus H cells independent of the radiation dose (15+/-7% versus 2183+/-2023%, P<0.01, H-R versus H cells). An oxygen enhancement ratio of 1.8 was calculated after irradiation from the retarded growth of H-R versus hypoxic HCSMCs. Production of reactive oxygen species by HCSMCs after irradiation increased by 15+/-2% in H-R cells versus 7+/-1% in H cells (P<0.05).Reoxygenation of hypoxic HCSMCs markedly amplifies growth-retarding effects of ionizing irradiation. On the basis of these findings, oxygenating radiosensitizers should be analyzed with regard to suitability for coronary brachytherapy to prevent restenosis.
CORRELATION OF LEFT VENTRICULAR NON-COMPACTED/ COMPACTED MASS RATIO AND CLINICAL OUTCOMES IN PATIENTS WITH LEFT VENTRICULAR NON-COMPACTION
Authors: Yongkasem Vorasettakarnkij, Daniel J. Verdini, Peerawut Deeprasertkul, Hector M. Medina, Alexander Goehler, Elkan F. Halpern, Waleed Ahmed, Shanmugam Uthamalingam, Amparo L. Figueroa, Gyongyi P. Major, Thomas J. Brady, David E. Sosnovik, Brian B. Ghoshhajra, Godtfred Holmvang
Journal: Journal of the American College of Cardiology (2011)
Prevalence and pathogenesis of pneumoconiosis in coal workers.
Authors: A G Heppleston
Journal: Environmental Health Perspectives (1988)

Dust dose and composition do not appear to account wholly for changes in the prevalence of coal workers' pneumoconiosis in Europe. In certain coal pits high progression evidently occurred with relatively low dust exposure or vice versa, whereas progression in relation to dust levels might be variable. Exceptionally high quartz concentrations occur in coal mine dust when pneumoconiosis may progress with unusual rapidity. Under such circumstances lesions resembling silicotic nodules may be found, but with the customarily lower levels of quartz the pathological features assume the form characteristic of coal workers. Morphological changes in relation to dust content of human and animal lungs, as well as cellular behavior, have not accounted completely for the epidemiological findings. Considering all the pathological evidence helps explain the pathogenesis of pneumoconiosis and vagaries of progression. The origin of progressive massive fibrosis cannot be explained simply in terms of dust burden or immunological features, and the role of an infective factor cannot be dismissed. Moreover, lipid secretion by alveolar epithelium introduces a new element that could affect the development of simple and complicated pneumoconiosis. In vitro, cytotoxicity appeared to be too variable for predictive purposes, though direct assay of fibrogenicity using the macrophage fibrogenic factor suggested that dust dose was more important than dust composition. Assessing individual susceptibility presents serious obstacles.
Hepatic encephalopathy treatment and its effect on driving abilities: A continental divide
Authors: Mette M. Lauridsen, Jasmohan Singh Bajaj
Journal: Journal of Hepatology (2015)

We read with great interest the review article on hepatic encephalopathy (HE) that, in addition to the recent EASL/AASLD guidelines, is informative about the spectrum of this disease [1,2]. We set out to evaluate the practice patterns of clinical HE experts worldwide (285 ISHEN members and authors of clinical HE articles in the last 5years) through a systematic electronic questionnaire focused on the management and effect on driving ability in HE. Results are summarized in the Table 1.
Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: Reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro
Authors: David M. Virshup, William H. Zinkham, Ronald L. Sirota, Winslow S. Caughey
Journal: American Journal of Hematology (1983)

Abstract Phenazopyridirie (PAP) causes a hemolytic anemia in normal individuals who receive an overdose or in patients with decreased renal function given therapeutic doses. There are no reports of PAP‐induced hemolysis in individuals with unstable hemoglobins. Therapeutic doses of PAP administered to a subject with Hb Zürich (His E7 (63) β→ Arg) caused a severe hemolytic anemia with many large Heinz bodies appearing in the red cells. Incubation of whole blood from three asymptomatic Hb Zürich subjects with PAP at a molar ratio of PAP/Hb of 1.3/1 produced a moderate to marked increase in methemoglobin (MHb) and Heinz body formation accompanied by a slight to moderate decrease in levels of reduced glutathione. The rates of MHb formation were proportional to the concentration of PAP. In two of the subjects the rates of formation of Heinz bodies and MHb were substantially higher than in the third subject. Red cells from five normal adults were not affected. In Hb Zürich red cells the affinity of the abnormal β chain for carbon monoxide is much greater than that of the normal α and β chains. The two subjects with higher rates of MHb and Heinz body formation were nonsmokers with in vivo carboxyhemoglobin (HbCO) levels of 4–6%. The third subject with low rates of MHb and Heinz body formation was a smoker with in vivo HbCO levels of 15–18%. Increasing levels of HbCO from 8.2% to 14.3% by the in vitro addition of CO caused a marked reduction in the rate of Heinz body formation and a moderate decrease in MHb formation. Rates of MHb formation similar to those observed in normal red cells occurred at HbCO percentages of 89.2 and 99.2. Red cells containing Hb Zürich are extremely sensitive to oxidative injury by PAP, either in vivo or in vitro. The degree of oxidative injury diminishes as the level of HbCO increases, a phenomenon that is enhanced by preferential binding of CO to the abnormal β subunit of Hb Zürich.
Recommendations from quality of life scales are not simple
Authors: M. E Hyland
Journal: BMJ (2002)

<h3>Background/Aims</h3> Vision impairment (VI) increases the risk of various comorbidities, including depression. However, the relationship between depression and VI is unclear, and existing findings are inconsistent. We therefore investigated the risk of depression in adults before and after their registration as visually impaired. <h3>Methods</h3> In this longitudinal, nationwide, retrospective cohort study, 131 434 patients (aged ≥18 years) with newly registered VI during 2005–2013 were evaluated using the Korean National Health Insurance Service database. Using 1:1 propensity score matching, randomly selected patients (control group) were compared with patients with VI (patient group) according to age, sex, residential area and household income. Each patient was tracked from 3 years before and 5 years after registration. The risk of depression before and after VI registration was evaluated using a conditional logistic regression model. <h3>Results</h3> The risk of depression gradually increased from 3 years before registration (OR, 1.186; 95% CI 1.089 to 1.290), then peaked at the time of registration (OR, 1.925; 95% CI 1.788 to 2.073), and then gradually decreased until 5 years after registration (OR, 1.128; 95% CI 1.046 to 1.216). Male patients, those with severe VI and those aged 18–29 years had a higher risk of depression. <h3>Conclusions</h3> Patients with VI had an increased risk of depression from 3 years before to 5 years after registration. Significant risk factors included severity, male sex and younger age. Thus, public mental health services are necessary to provide appropriate support and interventions to people before and after registration as visually impaired.
The importance of being naked from the elbow down
Authors: Ian A Laing
Journal: BMJ (2006)

One-time general consent for research on biological samples Opt out system for patients is optimal and endorsed in many countriesEditor-Wendler's valuable overview of empirical studies of patients' preferences about the use of residual (leftover) tissue for research is not complete. 1 The discussion has already been settled by legislation in many countries.In 2004 the Danish act on patient rights was amended with an opt out system for using residual tissue for research.In 2004 the US Office for Human Research Protections (OHRP) issued guidance that research on residual tissue which is anonymous to the researcher is not human subject research and therefore the tissue can be used without consent. 2Earlier the Dutch Federation of Medical Research Societies' code of conduct on research with residual tissue drafted with patients' organisations had an opt out system for research on samples anonymous to the researcher. 3 In the recent UK Human Tissue Act no form of consent is needed for the use of fully anonymous or coded (or linked) residual tissue that is anonymous to the researcher, provided that an ethical review board has permitted the study.The more restrictive provisions in the original bill were amended also because of pressure from patient groups afraid that research to their benefit would be hampered by the proposed consent system.Wendler emphasises autonomy and argues that one-time consent protects the autonomy of individuals and protects them from serious risks.There are two major arguments against this.Firstly, autonomy should be balanced against other values such as the interests of patients who might benefit from this research. 4 Secondly, autonomy as such cannot protect individuals from risks but only from risks they do want to carry.Research on residual tissue, whether anonymous or anonymously used and being coded, does not carry any risks to individuals.Ethical review boards should oversee that sufficient measures have been taken to ensure that the samples used in research remain anonymously used.It should be possible to enrich data from tissue research with patient data.Fully anonymising samples, as suggested by Wendler, is a waste of valuable information.
Early and Delayed 1-123 IMP SPECT in Epileptic Patients with Partial Seizures and Normal CT
Authors: MASASHI KAWAMURA, KENYA MURASE, MASAAKI KATAOKA, HISAO ITOH, MASAHIRO ISHINE, SACHIKO KAWAMURA, SHIGERU NAKATA, KEN HAMAMOTO
Journal: Clinical Nuclear Medicine (1991)

Forty-six epileptic patients with partial seizures and normal CT underwent 48 examinations of early and delayed SPECT using I-123 IMP in the interictal phase. One of them underwent a follow-up SPECT in a more stable state compared to the first SPECT. Another patient, with informed consent, underwent a follow-up SPECT in combination with pharmacologic activation with bemegride. Early SPECT was performed 30 minutes after an IMP Injection and delayed SPECT 4 to 4 1/2 hours later. Temporal changes in uptake pattern were visually classified into six types and compared with known patterns of SPECT uptake in relation to ischemic, hyperemic, and other changes. These were also correlated with the amount of epileptic activity seen on the EEG.
HbF production in β thalassaemia heterozygotes for the IVS-II-1 G→A β0-globin mutation. Implication of the haplotype and theGγ-158 C→T mutation on the HbF level
Authors: George V.Z. Dedoussis, Georgia D. Mandilara, Marina Boussiu, Aphrodite Loutradis
Journal: American Journal of Hematology (2000)

We studied the presence of the XmnI site and the β-globin haplotype in 24 individuals, carriers of the IVSII-1 G→A β0-globin mutation, of whom fourteen had no detectable levels of HbF, while ten coming from 5 families, presented HbF levels ranging from 1.7 to 9% of the total Hb. Of these β-thalassaemia heterozygotes with fetal hemoglobin, 6 were females and 4 were males with median HbF levels of 4.85% and 4% respectively, and an excess of Gγ chains (range Gγ/Aγ: 55/45–70/30). Of the group of carriers of β-thalassaemia with HbF < 0.1, in all cases except one, IVSII-1 mutation was found associated with XmnI polymorphic site. Haplotype analysis in these individuals revealed that in 10 cases IVSII-1 was linked with haplotype IIIb, in 1 case with haplotype IIIa, and in 3 cases with haplotype IX. On the other hand, in the group of carriers with measurable levels of HbF, IVSII-1 was always associated with haplotype IIIa and the XmnI site was either in-homozygous or the heterozygous state in-cis or in-trans with the mutated β-globin gene. In conclusion the results of the study of these families seem that XmnI site in-cis with the IVSII-1 does not induce HbF production when this β0-thalassaemia mutation is associated with IIIb or IX haplotype. On the other hand the Gγ −158 C→T mutation is associated with small amounts of HbF in IVSII-1 heterozygotes, when the β-globin mutation is linked to haplotype IIIa. Am. J. Hematol. 64:151–155, 2000. © 2000 Wiley-Liss, Inc.
Hemophagocytosis exacerbated by G‐CSF/GM‐CSF treatment in a patient with myelodysplasia
Authors: Sa Wang, Barbara A. Degar, Arthur Zieske, Nelofar Q. Shafi, Michal G. Rose
Journal: American Journal of Hematology (2004)

Abstract We describe a 75‐year‐old man with neutropenia in whom bone marrow aspirate and biopsy demonstrated hemophagocytosis associated with myelodysplasia (MDS). Therapy with granulocyte‐colony stimulating factor (G‐CSF) and granulocyte‐monocyte‐colony stimulating factor (GM‐CSF) caused splenomegaly and severe thrombocytopenia, which recurred upon rechallenge. We propose that myeloid growth factors may be detrimental in patients with MDS‐associated hemophagocytosis. Am. J. Hematol. 77:391–396, 2004. © 2004 Wiley‐Liss, Inc.
Relationship of Anthracycline-Free Interval to Outcomes in a Phase 3 Trial of Pegylated Liposomal Doxorubicin Plus Docetaxel Compared with Docetaxel Monotherapy in Patients with Advanced Breast Cancer Treated with Adjuvant Anthracycline.
Authors: J. Sparano, S. Zhuang, A. Londhe, K. Lantz, C. Lowery
Journal: Cancer Research (2009)

Abstract Background: An earlier report showed that pegylated liposomal doxorubicin (PLD) + docetaxel (D) improved time to progression (TTP) vs D alone in patients (pts) with advanced breast cancer (ABC) who had relapsed at least 1 year after adjuvant or neoadjuvant anthracycline therapy. (Sparano et al., SABC 2008, #80) This analysis evaluated whether the time between completion of adjuvant anthracycline therapy until relapse impacts overall outcome. We retrospectively examined outcomes in pts with an anthracycline-free (A-F) interval of 1 to 2 years and pts with an A-F of &amp;gt;2 years.Methods: 751 pts were randomly assigned to receive either D 75 mg/m2 (N=373) or PLD 30 mg/m2 followed by D 60 mg/m2 (N=378) every 21 days. Treatment was continued until disease progression or the occurrence of unacceptable toxicity. The primary endpoint was TTP and secondary endpoints included overall survival (OS), progression free survival (PFS), objective response rate (ORR), and safety. Pts were categorized into groups by anthracycline-free interval of 1-2 years or &amp;gt;2 years. Relationship between the interval and outcomes was examined by proportional hazards model for TTP, OS (updated as of 1-Dec-2008), and PFS.Results: Approximately 60% of pts in both treatment groups had A-F intervals of &amp;gt;2 years. Median TTP, OS, and PFS (months) by A-F interval groups are listed in the Table. A-F interval 1-2 years A-F interval &amp;gt;2 years D, n=151PLD+D, n=155HR (CI)*; P**D, n=221PLD+D, n=221HR (CI)*; P**TTP5.77.80.67 (0.52, 0.87); .0027.710.60.63 (0.50, 0.79); &amp;lt;.001OS15.817.90.90 (0.69, 1.16); .40424.722.91.10 (0.86, 1.40); .448PFS5.57.70.67 (0.52, 0.87); .0027.710.00.65 (0.51, 0.81); &amp;lt;.001ORR25%34%P=.086†27%36%P=.042† A-F interval 1-2 years, N=306 A-F interval &amp;gt;2 years, N=442 HR (CI)***; P**TTP6.6 8.9 0.74 (0.63, 0.88); .001OS17.2 23.4 0.63 (0.52, 0.75); &amp;lt;.001PFS6.5 8.7 0.74 (0.62, 0.87); &amp;lt;.001ORR30% 31% P=.826†*Proportional hazard model for PLD+D vs D; **Log-rank test; ***Proportional hazard model for &amp;gt;2 years vs ≤2 years A-F; †Cochran-Mantel-Haenszel test.Overall, HFS and stomatitis occurred more often in pts treated with PLD+D. The overall incidence of CHF was 1%.Conclusions: An A-F interval of &amp;gt;2 years reduced the risk for TTP, OS, and PFS, regardless of treatment. However, similar to results of the overall study, treatment with the combination PLD+D resulted in statistically significant improvement of TTP and PFS, but not OS, compared with D among pts with ABC, regardless of A-F interval. The addition of PLD to a D-based regimen is an active option for pts with ABC previously treated with adjuvant anthracycline regimens. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2095.