tbuckley/cabot-search huggingface dataset:
Effects of vasopressor agents and epoprostenol on systemic hemodynamics and oxygen transport in fulminant hepatic failure
Authors: Julia A. Wendon, Phillip M. Harrison, Richard Keays, Alexander E. Gimsson, Graeme J. M. Alexander, Roger Williams
Journal: Hepatology (1992)

Hypotension is a serious complication in patients with fulminant hepatic failure, because it is associated with tissue hypoxia and a further compromise to end-organ function. In this study we investigated the effects of epinephrine and norepinephrine on hemodynamics and oxygen transport variables in 30 patients with fulminant hepatic failure. All had a mean arterial pressure of less than 60 mm Hg, despite adequate intravascular filling pressures. Both epinephrine (n = 15) and norepinephrine (n = 15) improved mean arterial pressure (p < 0.001 epinephrine and norepinephrine), although this was not associated with a rise in oxygen delivery. Oxygen consumption fell (p<0.05 epinephrine, p<0.001 norepinephrine) because of a lower oxygen extraction ratio (p<0.01 epinephrine and norepinephrine). The addition of epoprostenol, a microcirculatory vasodilator, in 10 patients from each group led to an increase in oxygen consumption (p<0.001 epinephrine and norepinephrine) because of a rise in oxygen delivery (p<0.05 epinephrine, p<0.01 norepinephrine) and oxygen extraction ratio (p<0.01 epinephrine, p<0.001 norepinephrine), without a fall in mean arterial pressure. The fall in oxygen consumption after the institution of vasopressor therapy could exacerbate tissue hypoxia and thus contribute to further organ damage in an already susceptible patient. In patients with fulminant hepatic failure who are given vasopressor support, the addition of epoprostenol may prevent the development of tissue hypoxia. (HEPATOLOGY 1992;15:1067-1071).
A Phase I Study of Topical Tempol for the Prevention of Alopecia Induced by Whole Brain Radiotherapy
Authors: James M. Metz, Debbie Smith, Rosemarie Mick, Robert Lustig, James Mitchell, Murali Cherakuri, Eli Glatstein, Stephen M. Hahn
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Complete alopecia is a universal complication of whole brain radiation therapy which contributes to patient anxiety over treatment. Tempol, a nitroxide radioprotector, has been shown to protect against radiation-induced alopecia in an animal model. This phase Ib study was designed to evaluate the safety and side effect profile of topical Tempol in patients with brain metastases being treated with whole brain radiotherapy. Experimental Design: Twelve patients with metastatic cancer to the brain were enrolled in the study between October 2000 and February 2003. Tempol (70 mg/ml concentration solution) was applied topically to the scalp 15 minutes before and washed off immediately after the completion of each of 10 fractions of whole brain radiation. Pharmacokinetic studies to evaluate the systemic absorption of Tempol were performed. Patients were assessed for toxicity before, during, and after Tempol administration. A secondary end point of the study, hair retention, was also scored. Results: Eleven patients were treated with topical Tempol. Adverse events that were considered possibly, probably, or definitely related to Tempol, included asymptomatic grade 2 (two patients) and grade 1 (one patient) hypoglycemia, grade 1 forehead skin redness (one patient), grade 1 dry scalp (one patient), and grade 1 tingling sensation on the scalp (one patient). Tempol was not detected in blood samples from more than 50% of the patients. Mean maximum Tempol levels for individual patients at any time point varied from 0.4 to 3.1 μmol/L. Hair retention was localized to the base of the scalp where the Tempol solution pooled after application in the first four patients on the study. Subsequently, full scalp hair retention was seen in three of final five evaluable patients after gauze had been wrapped around the head to hold the solution against the scalp. Conclusions: This study demonstrates that topical application of Tempol to the scalp before whole brain radiation is safe and well tolerated. Evidence of protection against radiation-induced alopecia was observed. A phase II study that uses a gel formulation to increase the exposure of scalp to Tempol has been initiated.
In-flight Medical Emergencies
Authors: J. Martin V. Nicoll
Journal: JAMA (1989)

<h3>To the Editor.—</h3> From the statistics of in-flight deaths reported by Cummins et al,<sup>1</sup>one might infer that the problem is a minor one; however, serious illness that occurs during commercial air travel may be a much larger problem. Some of Cummins' coauthors have claimed that "all airlines... rely on the chance presence of a doctor competent to deal with the more serious emergency."<sup>2</sup>This is not necessarily the case.<sup>1,3</sup> However, as passengers, we have been requested to attend to in-flight medical emergencies on several different occasions. We have found that the crew are only too relieved to shift the responsibility for the patient onto any co-opted physician-passenger. On a recent intercontinental flight both a psychiatrist and one of the authors (K.R.E.), an anesthesiologist, responded to the call for help. The psychiatrist, who arrived first, pronounced that the patient was "just fine." The anesthesiologist found that this
Therapy of Staphylococcus aureus Bacteremia Associated with a Removable Focus of Infection
Authors: Paul B. Iannini, Kent Crossley
Journal: Annals of Internal Medicine (1976)

We did a retrospective study of Staphylococcus aureus bacteremia--from removable foci of infection--treated with short course antimicrobial therapy. Patients with S. aureus endocarditis were excluded from our study. The majority of patients had sepsis from intravascular devices. After removal of the focus of bacteremia, antibiotics were administered for a mean period of 15.2 days. There were no relapses, and no patient developed endocarditis. A 10- to 21-day antibiotic regimen can be curative in S. aureus bacteremia associated with a removable focus of infection.
Decreased myofilament responsiveness in myocardial stunning follows transient calcium overload during ischemia and reperfusion.
Authors: J P Carrozza, L A Bentivegna, C P Williams, R E Kuntz, W Grossman, J P Morgan
Journal: Circulation Research (1992)

The purpose of this study was to test the hypothesis that abnormal intracellular calcium handling characterizes myocardial stunning. Isolated, isovolumic, buffer-perfused ferret hearts were loaded with the bioluminescent calcium indicator aequorin for simultaneous measurement of individual calcium transients and left ventricular pressure. After 15 minutes of global ischemia and 20 minutes of reperfusion, left ventricular developed pressure was significantly reduced (75 +/- 7 versus 93 +/- 6 mm Hg, p < 0.05). During ischemia, [Ca2+]i levels were significantly elevated compared with preischemic levels, both during systole (1.38 +/- 0.31 versus 0.88 +/- 0.2 microM, p < 0.05) and end diastole (0.85 +/- 0.16 versus 0.38 +/- 0.13 microM, p < 0.05). Early during reperfusion, [Ca2+]i was also significantly elevated during systole (1.63 +/- 0.44 versus 0.88 +/- 0.20 microM, p < 0.05) and end diastole (0.75 +/- 0.15 versus 0.38 +/- 0.13 microM, p < 0.05). After 20 minutes of reperfusion, myocardial stunning occurred, but [Ca2+]i was not significantly different from preischemic levels. Thus, myocardial stunning does not result from decreased levels of activator calcium. The force-pCa relation generated by the stunned hearts was shifted downward compared with that generated by the control hearts, consistent with a decrease in maximum calcium-activated force (Fmax). At steady state during tetanus, the decrease in Fmax was confirmed, but there was no significant difference in the slope of the force-pCa relation of the stunned hearts versus controls. Thus, we conclude that stunned myocardium is characterized by decreased Fmax without desensitization of the myofilaments to [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance
Authors: Myriam Alcalay, Enrico Tiacci, Roberta Bergomas, Barbara Bigerna, Elisa Venturini, Simone P. Minardi, Natalia Meani, Daniela Diverio, Loris Bernard, Laura Tizzoni, Sara Volorio, Lucilla Luzi, Emanuela Colombo, Francesco Lo Coco, Cristina Mecucci, Brunangelo Falini, Pier Giuseppe Pelicci
Journal: Blood (2005)
Tamoxifen Induction of Apoptosis in Estrogen Receptor-Negative Cancers: New Tricks for an Old Dog?
Authors: E. P. Gelmann
Journal: JNCI Journal of the National Cancer Institute (1996)

figure represents the added cost of HAI treatment as compared with IVC treatment. The cost-effectiveness of HAI could then be determined by the ratio of the incremental cost of HAI to the average quality-adjusted time gained (in years). The resulting figure represents the cost per quality-adjusted year gained. This figure could be used to determine whether HAI treatment is cost-effective. The use of assessment tools and procedures similar to those mentioned above is becoming increasingly important in clinical cancer research. At a minimum, future clinical trials should carefully collect data regarding toxicity grade and duration in addition to the usual clinical end points. The use of a quality-oflife instrument and the tracking of costs longitudinally over the course of a study are also strongly recommended. The soon-tobe-activated Cancer and Leukemia Group B randomized clinical trial comparing HAI versus systemic therapy represents an important step in this direction. That study will collect data on quality of life, utility coefficients, and economic costs, as well as clinical end points. When the study is completed, we can expect to have a meaningful evaluation of clinical outcome, quality-of-life trade-offs, and economic costs. The current meta-analysis of HAI treatment for liver metastases from colorectal cancer provides useful and insightful results regarding this treatment regimen. The authors have done an excellent job of evaluating the data and of discussing the implications and limitations of their results. Their discussion also highlights the need to evaluate trade-offs in clinical research as well as the need to continue developing practical tools and analytic methods for accomplishing this.
The effect of γ-tocotrienol on human airway smooth muscle cell proliferation and migration
Authors: Tomoya Harada, Akira Yamasaki, Hiroki Chikumi, Kiyoshi Hashimoto, Ryota Okazaki, Yasuyuki Hasegawa, Masanari Watanabe, Andrew Halayko, Eiji Shimizu
Journal: European Respiratory Journal (2013)

Background  Vitamin E is known to have antioxidant activity and there are eight different forms of Vitamin E (α,β,γ and δ tocopherol and tocotrienol). Clinical trials using tocopherol supplementation for patients with asthma to assess impact of antioxidant activity have yielded equivocal results. Of note, the tocotrienol form of vitamin E has greater antioxidant activity than tocopherol, this manifest through several biological effects in vivo and in vitro. Therefore, we tested the effect of tocotrienol on human airway smooth muscle (ASM) cell growth and migration, which play an important role in airway remodeling in asthma.  Methods: We measured PDGF-BB-induced ASM cell proliferation using colorimetric assay by Cell counting kit-8 and ASM cell migration by transwell migration assay. We also assessed the effect of γ-tocotrienol (an isoform of tocotrienol), on ASM cell proliferation and migration.  Results: PDGF-BB-induced ASM cell proliferation and migration was significantly inhibited by γ-tocotrienol. This effect was associated with an inhibition of RhoA activation, but had no impact on activation of p42/p44 mitogen-activated protein kinase (MAPK) or Akt1. In follow up studies we confirmed that pharmacological inhibition of Rho kinase activity was sufficient to inhibit ASM cell proliferation and migration induced by PDGF-BB.  Conclusion: These results indicate that γ-tocotrienol could have therapeutic effects related to airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.
Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?
Authors: F Briet, P Pochart, P Marteau, B Flourie, E Arrigoni, J C Rambaud
Journal: Gut (1997)

Background —Uncontrolled studies of lactose intolerant subjects have shown that symptom severity decreases after chronic lactose consumption. Adaptation of the colonic flora might explain this improvement. Aims —To compare the effects of regular administration of either lactose or sucrose on clinical tolerance and bacterial adaptation to lactose. Methods —Forty six lactose intolerant subjects underwent two 50 g lactose challenges on days 1 and 15. Between these days they were given 34 g of lactose or sucrose per day, in a double blind protocol. Stool samples were obtained on days 0 and 14, to measure faecal β-galactosidase and pH. Symptoms, breath H 2 excretion, faecal weight and electrolytes, and orofaecal transit time were assessed. Results —Except for faecal weight, symptoms were significantly milder during the second challenge in both groups, and covariance analysis showed no statistical difference between them. In the lactose group, but not in the sucrose group, faecal β-galactosidase activity increased, pH dropped, and breath H 2 excretion decreased. Conclusion —Bacterial adaptation occurred when lactose intolerant subjects ingested lactose for 13 days, and all symptoms except diarrhoea regressed. Clinical improvement was also observed in the control group which displayed no signs of metabolic adaptation. This suggests that improved clinical tolerance may be just a placebo effect.
Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials
Authors: C. Heijl, L. Harper, O. Flossmann, I. Stucker, D. Scott, R. A. Watts, P. Hoglund, K. Westman, A. Mahr
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Because standard immunosuppressive treatment for antineutrophil cytoplasm antibody-associated vasculitis (AAV) (granulomatosis with polyangiitis (Wegener9s) (GPA) and microscopic polyangiitis (MPA)) has been associated with a significant risk of developing cancer, the cancer incidence of treated AAV patients was assessed. <h3>Methods</h3> This analysis concerned 535 patients with newly diagnosed AAV from 15 countries who had been enrolled between 1995 and 2002 in four European clinical trials. Over the period 2004–7, study participants9 follow-up events were updated, including cancers diagnosed. Age, sex and area-standardised incidence ratios (SIR) and their 95% CI were calculated by linkage to five national cancer databases. <h3>Results</h3> During the 2650 person-years9 observation period, 50 cancers were diagnosed in 46 patients. SIR (95% CI) were 1.58 (1.17 to 2.08) for cancers at all sites, 1.30 (0.90 to 1.80) for cancers at all sites excluding non-melanoma skin cancer (NMSC), 2.41 (0.66 to 6.17) for bladder cancer, 3.23 (0.39 to 11.65) for leukaemia, 1.11 (0.03 to 6.19) for lymphoma and 2.78 (1.56 to 4.59) for NMSC. Subgroup SIR for cancers at all sites were 1.92 (1.31 to 2.71) for GPA and 1.20 (0.71 to 1.89) for MPA. <h3>Conclusions</h3> Cancer rates for AAV patients treated with conventional immunosuppressive therapy exceeded those expected for the general population. This cancer excess was largely driven by an increased incidence of NMSC. The smaller cancer risk magnitude in this cohort, compared with previous studies, might reflect less extensive use of cyclophosphamide in current treatment protocols. Longer follow-up data are warranted to appraise the risk of developing cancers later during the course of AAV.
CD8+ T cells Reactive to Survivin Antigen in Patients with Multiple Myeloma
Authors: Matthias Grube, Stephanie Moritz, Ellen C. Obermann, Katayoun Rezvani, Andreas Mackensen, Reinhard Andreesen, Ernst Holler
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Survivin is a member of the inhibitors of apoptosis family and is overexpressed in different types of malignancies. Cytotoxic T cells recognizing survivin epitopes can be elicited in vitro and by vaccination in patients with leukemia, breast cancer, and melanoma. We did this study to investigate whether survivin-specific CD8+ T cells occur in patients with multiple myeloma. Experimental Design: An HLA-A2.1–binding survivin peptide was used to detect peptide-specific T cells by a quantitative real-time PCR to measure antigen-specific IFN-γ mRNA expression in 23 patients with myeloma and 21 healthy volunteers. T cells producing IFN-γ in response to survivin were further analyzed for expression of CD45RA and CCR7 to determine phenotypic characterization. Additional immunohistochemical analyses of survivin antigen expression in bone marrow specimens of patients was done. Results: T cells recognizing HLA-A2.1–binding survivin peptide were detected in 9 of 23 patients and in 1 of 21 healthy volunteers. Survivin-reactive T cells were identified as terminally differentiated effector T cells (CD8+, CD45RA+, and CCR7−). Positive survivin expression of myeloma cells in bone marrow specimens was shown in 7 of 11 patients. Conclusion: We provide, for the first time, evidence of T cell reactivity against survivin antigen in patients with multiple myeloma. Our data suggest the immunogenicity of survivin antigen in multiple myeloma and that immunotherapeutic strategies using survivin as a target antigen might be an option for patients with this disease.
Divergent and convergent evolution after a common-source outbreak of hepatitis C virus
Authors: Stuart C. Ray, Liam Fanning, Xiao-Hong Wang, Dale M. Netski, Elizabeth Kenny-Walsh, David L. Thomas
Journal: The Journal of Experimental Medicine (2005)

The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak. We compared sequences present in serum obtained 18–22 yr after infection to sequences present in the shared inoculum and found that HCV evolved along a distinct path in each woman. Amino acid substitutions in known epitopes were directed away from consensus in persons having the HLA allele associated with that epitope (immune selection), and toward consensus in those lacking the allele (reversion). These data suggest that vaccines for genetically diverse viruses may be more effective if they represent consensus sequence, rather than a human isolate.
Excursion-volume relation of the right hemidiaphragm measured by ultrasonography and respiratory airflow measurements.
Authors: E Cohen, A Mier, P Heywood, K Murphy, J Boultbee, A Guz
Journal: Thorax (1994)

BACKGROUND--Although real time ultrasonography has been used in the last decade to record diaphragmatic motion, the relation between diaphragmatic excursion and different inspired volumes (VT) has not been assessed by ultrasound. METHODS--Ten normal subjects were studied in the supine posture. Diaphragmatic excursion and VT were assessed simultaneously by M mode ultrasonography and respiratory airflow measurements at different inspired volumes. Ultrasound recordings of the movement of the right hemidiaphragm were carried out in the longitudinal plane subcostally. The transducer was held in a fixed position by a frame, built especially to eliminate any artefactual movement caused by outward motion of the anterior abdominal wall on inspiration. RESULTS--Mean (SD) maximal diaphragmatic excursion recorded was 6.0 (0.7) cm. Inspired volumes ranged from 15(5%) to 87(10%) of the subjects9 inspiratory capacity. A linear relation between diaphragmatic excursion and VT was found in all subjects (r = 0.976-0.995). The regression line had a slope of 1.66 (0.24) cm/l. This slope had no correlation with either the height (r = 0.007) or weight (r = 0.143) of the subjects. In five subjects in whom diaphragmatic excursion could be recorded at volumes near total lung capacity, the relation between diaphragmatic excursion and VT became alinear at very high lung volumes. CONCLUSIONS--The relation between diaphragmatic excursion and VT was linear between 15(5%) and 87(10%) of inspiratory capacity. Ultrasonography of the diaphragm is a simple technique that could be applied in the clinical investigation of patients with suspected abnormalities of diaphragmatic movement.
The Impact of Neurotechnology on Rehabilitation
Authors: T.W. Berger, G. Gerhardt, M.A. Liker, W. Soussou
Journal: IEEE Reviews in Biomedical Engineering (2008)

This paper present results of a multi-disciplinary project that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for the formation of long-term memories. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease) and is considered to underlie the memory deficits related to these neurological conditions. The essential goals of the multi-laboratory effort include: (1) experimental study of neuron and neural network function-how does the hippocampus encode information? (2) formulation of biologically realistic models of neural system dynamics-can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event? (3) microchip implementation of neural system models-can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization? and (4) creation of hybrid neuron-silicon interfaces-can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, we are realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis. A proof-of-concept will be presented in which the CA3 region of the hippocampal slice is surgically removed and is replaced by a microchip model of CA3 nonlinear dynamics-the "hybrid" hippocampal circuit displays normal physiological properties. How the work in brain slices is being extended to behaving animals also will be described.
Increased blood level of prostaglandin-like substances during cardiopulmonary bypass in the dog
Authors: A. CEDRO, K. HERBACZYNSKA-CEDRO
Journal: Cardiovascular Research (1978)

Total heart-lung bypass (TBP) for open-heart surgery is often accompanied by a progressive reduction of systemic blood pressure. Since the lung is the main site of elimination of prostaglandins (PGs) from venous blood, TBP may lead to an increase in blood content of vasodilator PGs. TBP was performed in dogs and blood level of prostaglandinlike substances (PLS) was monitored continuously by a bio-assay method. The concentration of PLS increased during TBP to 0.8 ng.cm(-3) blood (in PGE2 equivalents). Restoration of normal circulation led to the disappearance of PLS from the blood. The increase in PLS during TBP was abolished by indomethacin. This was invariably accompanied by elevation of systemic blood pressure. It is suggested that an increased concentration of vasodilator PLS during TBP may contribute to the hypotension observed in total body perfusion.