tbuckley/cabot-search huggingface dataset:
VO2 equations revised: Is the use of assumed oxygen consumption acceptable?
Authors: Susanna Desole, Klemens Dolp, Christian M. Kähler
Journal: European Respiratory Journal (2012)

LaFarge/Miettinen's formula for the assumption of oxygen consumption (VO2) is one of the most used in hemodynamic calculations. Considering the importance of VO2 for the calculation of hemodynamics needed for disease evaluation (e.g. pulmonary hypertension), the need for an acceptable agreement between assumed and measured VO2 becomes obvious. A well known variation of the original formula is the one by Bergstra. In both equations, age, sex and BSA are factors determining the VO2, plus the heart rate (HR) in the original formula.

We compared directly measured VO2 with values calculated by both the LaFarge/Miettinen and the Bergstra equations.

VO2 of 122 volunteers (20-65y) was directly measured by the Innocor™(Innovision). VO2 was then recalculated by both the equations. Directly measured VO2 (VO2INN) was 363±84ml/min in males, 224±52ml/min in females. VO2 calculated by Bergstra was 298±24ml/min in males, and 233±24ml/min in females. VO2 by LaFarge/Miettinen was 258±24ml/min in males, 182±21ml/min in females. Direct comparison of VO2INN with calculated VO2 showed significant differences between all the methods. Factors found to be influencing the VO2 in our cohort included sex, HR and BSA whereas age seemed to have no effects. Significant correlations were found between VO2 and hemoglobin, oxygen saturation (SpO2), fitness level and systolic blood pressure.

Comparison of directly measured VO2 values with assumed data obtained by both the LaFarge/Miettinen and Bergstra equations showed that none of the formula is satisfying in terms of agreement with measured data. Using VO2 equations may result in major bias of hemodynamics and we therefore urge that resulting data should be interpreted critically.
Histochemical Studies in Atherogenesis: Human Aortas
Authors: FREDERICK T. ZUGIBE, KENNETH D. BROWN
Journal: Circulation Research (1960)

There have been many conflicting reports concerning the relationships of lipid, acid mucopolysaccharides, and elastic changes in the early pathology of atherosclerosis. Various new histochemical methods have been applied to grossly normal and early lesions of aortas of 50 individuals ranging from fetuses to 40 years of age with a view to illuminating these problems. The following paper presents our results of these studies.
Evidence for Male-Driven Evolution in Drosophila
Authors: D. Bachtrog
Journal: Molecular Biology and Evolution (2008)

In several vertebrate taxa studied to date, mutation rates are higher in males than females (male-driven evolution). The male-to-female mutation rate (alpha) can be estimated by contrasting DNA divergence data at X-linked, Y-linked, and autosomal loci. Previous studies in Drosophila, comparing X-linked and autosomal divergence, have found no evidence for male-driven evolution in this genus. Here, I compare levels of nucleotide divergence between homologous X- and Y-linked loci in Drosophila miranda. Using divergence at both synonymous sites and at short introns, I estimate alpha to be approximately 2. This study thus provides the first evidence for male-biased mutation rates outside vertebrates, supporting the view that DNA sequence evolution is male driven in a wide variety of taxa.
Spectrum of immunodeficiency in HIV-1-infected patients with pulmonary tuberculosis in Zaire
Authors: Y Mukadi, J.H Perriëns, M.E St Louis, C Brown, R.W Ryder, J.H Perriëns, F Portaels, P Piot, J.H Perriëns, J-C Willame, M.E St Louis, R.W Ryder, C Brown, J Prignot, F Pouthier, J-C Willame, M Kaboto
Journal: The Lancet (1993)
CYTOCHROME P-450 3A4: Regulation and Role in Drug Metabolism
Authors: F. Peter Guengerich
Journal: The Annual Review of Pharmacology and Toxicology (1999)

▪ Abstract Cytochrome P-450 (P-450) 3A4 is the most abundant P-450 expressed in human liver and small intestine. P-450 3A4 contributes to the metabolism of approximately half the drugs in use today, and variations in its catalytic activity are important in issues of bioavailability and drug-drug interactions. The gene is known to be inducible by barbiturates, glucocorticoids, and rifampicin in humans and in isolated hepatocytes, although the mechanism remains unclear. The 5′-untranslated region includes putative basal transcription element, hepatocyte nuclear factor, p53, AP-3, glucocorticoid regulatory element, pregnane X receptor, and estrogen receptor element sequences. Recently, the GRE element has been shown to act in a classic glucocorticoid response. Several issues remain to be resolved regarding the catalytic activity of the P-450 3A4 protein, including rate-limiting steps and the need for cytochrome b 5 , divalent cations, and acidic phospholipid systems for optimal activity. Another issue involves the basis of the homotropic and heterotropic cooperativity seen with the enzyme. The in vivo significance of these findings remains to be further established. In addition to more basic studies on P-450 3A4, several areas of practical interest to the pharmaceutical industry require development.
Deterioration of health-related quality of life and fatigue in patients with chronic hepatitis C: Association with demographic factors, inflammatory activity, and degree of fibrosis
Authors: Gerlinde Teuber, Arne Schäfer, Jasmin Rimpel, Kathrin Paul, Christian Keicher, Michael Scheurlen, Stefan Zeuzem, Michael R. Kraus
Journal: Journal of Hepatology (2008)
The Effect of Mobile Element IS10 on Experimental Regulatory Evolution in Escherichia coli
Authors: D. M. Stoebel, C. J. Dorman
Journal: Molecular Biology and Evolution (2010)

Mobile genetic elements are widespread in bacteria, where they cause several kinds of mutations. Although their effects are on the whole negative, rare beneficial mutations caused by insertion sequence elements are frequently selected in some experimental evolution systems. For example, in earlier work, we found that strains of Escherichia coli that lack the sigma factor RpoS adapt to a high-osmolarity environment by the insertion of element IS10 into the promoter of the otsBA operon, rewiring expression from RpoS dependent to RpoS independent. We wished to determine how the presence of IS10 in the genome of this strain shaped the evolutionary outcome. IS10 could influence the outcome by causing mutations that confer adaptive phenotypes that cannot be achieved by strains without the element. Alternatively, IS10 could influence evolution by increasing the rate of appearance of certain classes of beneficial mutations even if they are no better than those that could be achieved by a strain without the element. We found that populations evolved from an IS10-free strain did not upregulate otsBA. An otsBA-lacZY fusion facilitated the recovery of a number of mutations that upregulate otsB without involving IS10 and found that two caused greater fitness increases than IS10 insertion, implying that evolution could have upregulated otsBA in the IS10-free strain. Finally, we demonstrate that there is epistasis between the IS10 insertion into the otsBA promoter and the other adaptive mutations, implying that introduction of IS10 into the otsBA promoter may alter the trajectory of adaptive evolution. We conclude that IS10 exerts its effect not by creating adaptive phenotypes that could not otherwise occur but by increasing the rate of appearance of certain adaptive mutations.
Macrophages elicited with heat-killed bacillus Calomette-Guérin protect C57BL/6J mice against a syngeneic melanoma.
Authors: V H Freedman, T A Calvelli, S Silagi, S C Silverstein
Journal: The Journal of Experimental Medicine (1980)

We have demonstrated that a murine cytotoxic peritoneal cell can be elicited by intraperitoneal immunization with heat-killed Mycobacterium bovis, strain Bacillus Calmette-Guérin (BCG). When these cells are injected together with cells of clone B(5)59 of B16 melanoma in a Winn-type transfer assay into syngeneic C57BL/6J mice, the tumorigenic potential of the melanoma is completely abrogated. Similarly, mice immunized intraperitoneally with dead BCG are protected against intraperitoneal challenge with a number of B16 melanoma cells sufficient to cause tumors in 100% of control mice. However, mice immunized intraperitoneally with dead BCG are not protected against tumor formation when B16 melanoma cells are injected subcutaneously. Co-injection of BCG-elicited peritoneal cells with B16 melanoma cells into nude or sublethally irradiated (650 rad) mice inhibits tumor formation in > 85% of the mice, indicating that additional participation of host bone marrow- or thymus-derived leukocytes is not required to eradicate the tumor implant. The effector cell in the BCG-induced peritoneal exudate is adherent and phagocytic and is a mononuclear phagocyte. Nonadherent lymphoid cells from the same BCG-induced peritoneal exudate and from thioglycollate-broth-elicited granylocytes and macrophages neither prevent nor delay B16 tumor formation.
Narrow‐band (TL‐01) ultraviolet B phototherapy for chronic plaque psoriasis: three times or five times weekly treatment?
Authors: None Dawe, None Wainwright, None Cameron, None Ferguson
Journal: British Journal of Dermatology (1998)

Three and five times weekly narrow‐band TL‐01 (311–313 nm) ultraviolet (UV) B phototherapy regimens for chronic plaque psoriasis were compared in a randomized, observer‐blinded, half‐body, within‐patient paired study. Twenty‐one patients [13 men, eight women, age range 21–68 years, skin phototypes I (two patients), II (14) and III (five)] entered the study. Sixteen reached clearance or minimal residual activity (MRA) on both sides. Of the other five, three withdrew because they did not reach clearance or MRA on the 5 × weekly side by a maximum of 30 treatments, one when he was satisfied with moderate improvement and one because of repeated failure to attend. Those who completed treatment reached clearance or MRA after a median of 35 days with 5 × weekly treatment compared with 40 days with 3 × weekly treatment (P = 0.007), but required a median of 23.5 compared with 17 UVB exposures (P = 0.001) and 94 minimal erythema dose multiples (MEDs) compared with 64 MEDs (P = 0.01). Fifteen (of 16) developed at least one episode of well‐demarcated erythema during 5 × weekly treatment compared with just three of 16 treated 3 × weekly (P < 0.001). There was no significant difference between regimens in duration of remission. For this skin phototype I–III population, the more rapid clearance of psoriasis with 5 × weekly phototherapy is not, for the majority of patients, sufficient to justify the extra exposures and higher UVB dose. We no longer use 5 × weekly phototherapy for psoriasis.
Treatment of limited-stage small-cell lung cancer with cyclophosphamide, doxorubicin, and vincristine with or without etoposide: a randomized trial of the North Central Cancer Treatment Group.
Authors: J R Jett, L Everson, T M Therneau, J E Krook, R J Dalton, R F Marschke, M H Veeder, S F Brunk, J A Mailliard, D I Twito
Journal: Journal of Clinical Oncology (1990)

In this randomized study involving patients with limited-stage small-cell lung cancer (LD-SCC), we compared treatment with either cyclophosphamide; doxorubicin, and vincristine (CAV) or CAV plus etoposide (CAVE). All patients received identical thoracic radiation consisting of 3,750 cGy in 15 fractions and prophylactic cranial radiation (3,000 cGy in 10 fractions). Among 231 evaluable patients, the two treatment arms were well matched with respect to sex, age, performance score, and presence or absence of heart disease. A major regression (REGR) was observed in 83% of all patients and a complete response (CR) in 60%. There was no difference in the response rate between the two treatment regimens. The median time to progression is 10.4 months (95% confidence interval [Cl], 8.9 to 12 months) for CAVE versus 8.9 months (95% Cl, 7.9 to 10.4 months) for CAV (P = .04). The median survival is 15.1 months (95% Cl, 11.7 to 17.8 months) for CAVE versus 12.4 months (95% Cl, 11 to 14.4 months) for CAV. This difference is not significantly different (P = .13). Toxicity was primarily myelosuppression and was significantly greater for the four-drug regimen. Fatal treatment-related toxicity was observed in two patients on the CAVE regimen and no treatment-related deaths were observed on the CAV treatment. In conclusion, the addition of etoposide to the CAV regimen resulted in increased toxicity but did not lead to a meaningful improvement in survival.
Randomized Phase II Trial of Docetaxel Plus Cetuximab or Docetaxel Plus Bortezomib in Patients With Advanced Non–Small-Cell Lung Cancer and a Performance Status of 2: CALGB 30402
Authors: Rogerio Lilenbaum, Xiaofei Wang, Lin Gu, Jeffrey Kirshner, Keith Lerro, Everett Vokes
Journal: Journal of Clinical Oncology (2009)

Purpose A randomized phase II trial of two novel treatment strategies in the first-line management of advanced non–small-cell lung cancer patients with performance status (PS) 2. Patients and Methods Patients were assigned to docetaxel 30 mg/m 2 on days 1, 8, and 15 every 28 days in combination with either cetuximab 400 mg/m 2 loading dose followed by 250 mg/m 2 weekly (D + C) or bortezomib 1.6 mg/m 2 on days 1, 8, and 15 every 28 days (D + B) for up to 4 cycles. Patients with responding or stable disease continued cetuximab or bortezomib until progression. The primary end point was progression-free survival (PFS) rate at 6 months. Results Sixty-four patients were enrolled and 59 were included in this analysis. Complete or partial response rates were 13.3% and 10.3% for D + C and D + B, respectively. Median PFS was 3.4 months in the D + C arm and 1.9 months in the D + B arm. Corresponding figures for 6-month PFS were 27.8% and 13.8% and 5.0 and 3.9 months for median survival, respectively. Grade 3/4 hematologic toxicity was 16% for D + C and 21% for D + B, whereas nonhematologic toxicities were observed in 63% and 44% of patients, respectively. There was one treatment-related death in each arm. Conclusion These results confirm the poor prognosis associated with a PS of 2 and the difficulty in translating recent advances in targeted therapy to this subset of patients. While the results in the D + C arm are numerically superior, neither combination met the prespecified PFS end point to justify further research in this setting.
Gene Therapy for Heart Failure
Authors: Lisa Tilemann, Kiyotake Ishikawa, Thomas Weber, Roger J. Hajjar
Journal: Circulation Research (2012)

Congestive heart failure accounts for half a million deaths per year in the United States. Despite its place among the leading causes of morbidity, pharmacological and mechanic remedies have only been able to slow the progression of the disease. Today's science has yet to provide a cure, and there are few therapeutic modalities available for patients with advanced heart failure. There is a critical need to explore new therapeutic approaches in heart failure, and gene therapy has emerged as a viable alternative. Recent advances in understanding of the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, have placed heart failure within reach of gene-based therapy. The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a), along with the start of more recent phase 1 trials, opens a new era for gene therapy for the treatment of heart failure.
Influence of intimal dissection on restenosis after successful coronary angioplasty.
Authors: P P Leimgruber, G S Roubin, H V Anderson, C E Bredlau, H B Whitworth, J S Douglas, S B King, A R Greuntzig
Journal: Circulation (1985)

We studied 986 patients who underwent follow-up angiography after successful percutaneous transluminal coronary angioplasty (PTCA) to determine the influence of uncomplicated intimal dissection on restenosis rate. Angiographic evidence of intimal dissection after PTCA was present in 248 patients or 25%. After a mean follow-up time of 7 +/- 5 months (SD) the restenosis rate in patients without intimal dissection was 30% compared with 24% in patients with intimal dissection (p = .08). Patients with available transstenotic pressure gradients were divided according to the hemodynamic result into two subgroups: those with final gradients at the conclusion of PTCA of 15 mm Hg or less (n = 638) and those with gradients greater than 15 mm Hg (n = 244). Patients with intimal dissection had a significantly lower restenosis rate than patients without intimal dissection if the final gradient was 15 mm Hg or less (19% vs 28%; p less than .05). If the final gradient was greater than 15 mm Hg, the presence or absence of intimal dissection had no significant influence on restenosis rate, which was 35% and 39%, respectively (p = NS). We conclude that an uncomplicated intimal dissection after a successful coronary angioplasty has no adverse influence on angiographic restenosis. An excellent angiographic long-term outcome can be expected if the intimal dissection is associated with a favorable hemodynamic result.
Detection of Granulocyte–Macrophage Colony-Stimulating Factor in Patients with Pulmonary Alveolar Proteinosis
Authors: MARTHA SUE CARRAWAY, ANDREW J. GHIO, JACQUELINE D. CARTER, CLAUDE A. PIANTADOSI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Pulmonary alveolar proteinosis (PAP) is an idiopathic lung disease in which the alveolar spaces are filled with surfactant. Recently, it has been proposed that PAP is caused by deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) because GM-CSF-knockout mice develop the disease. To examine this possibility, we tested the two hypotheses that lung GM-CSF levels are low and that alveolar macrophages (AM) do not respond to GM-CSF in patients with PAP. Data from 10 adult patients with PAP who underwent therapeutic whole-lung lavage were compared with those of 10 healthy volunteers who underwent bronchoalveolar lavage (BAL) by fiberoptic bronchoscopy. Bronchoalveolar lavage fluid (BALF) and plasma were collected and analyzed for total protein and levels of GM-CSF, interleukin-3, and tumor necrosis factor (TNF)-alpha. Isolated AM were cultured with or without lipopolysaccharide (LPS) or GM-CSF, and production of GM-CSF and TNF-alpha was measured after 24 h. GM-CSF in BALF and plasma was higher in PAP than in control subjects (p </= 0.05), and was detectable under both reducing and nonreducing conditions as a 28-kD protein in BALF from the PAP patients. GM-CSF release by unstimulated AM from PAP patients was higher than in cells from control subjects, but the responses to LPS were similar. Mean TNF-alpha release by AM in response to GM-CSF was higher in control subjects than in PAP patients due to a low response in three patients. In conclusion, unbound immunoreactive GM-CSF is detectable in BALF and plasma of PAP patients. Most PAP patients also had intact AM responses to GM-CSF, although some may have had defects in GM-CSF receptor or signal-transduction mechanisms. Although these data exclude lack of GM-CSF production as a common etiology of human PAP, defects in GM-CSF function in PAP are under investigation.
Pathogenesis of experimental pulmonary alveolar proteinosis
Authors: B. Corrin, E. King
Journal: Thorax (1970)

Rats exposed to various airborne dusts developed a condition identical to pulmonary alveolar proteinosis as seen in man. The experimental condition developed through a stage of endogenous lipid pneumonia, characterized by numerous large foamy macrophages widely distributed throughout the lung. These cells broke down to release a finely granular material which finally condensed to reproduce the appearances of alveolar proteinosis. Electron microscopy indicated that the alveolar material was produced by type II pneumocytes and may therefore represent pulmonary surfactant. A study of the dust-handling mechanism showed that in affected animals macrophage mobility was seriously impaired.
Altered pattern of cytokine production by peripheral blood CD2+ cells from B chronic lymphocytic leukemia patients
Authors: Eduardo Reyes, Alfredo Prieto, Flavio Carrión, Julio García-Suarez, Fatima Esquivel, Cristina Guillén, Melchor Alvarez-Mon
Journal: American Journal of Hematology (1998)

To determine if activation-induced cytokine production is altered in CD2+ lymphocytes from B-CLL patients, cytokine levels were determined by ELISA in supernatants of PHA-stimulated cultures of CD2+ cells from 33 B-CLL patients and 22 healthy controls. The production of Interferon γ (IFN-γ) and Tumor Necrosis Factor (TNF-α) by mitogen-activated CD2+ lymphocytes from B-CLL patients was higher than that found in healthy controls, while no differences were found in TNF-β production. IFN-γ and TNF-α levels determined at 72 h in PHA-stimulated CD2+ cell cultures from B-CLL patients statistically correlated with the percentages of CD3+CD45RO+ and CD3−CD56+ lymphocytes, respectively. Although there were differences in the production kinetics of interleukins (ILs) 2 and 4 between B-CLL patients and the healthy controls, no differences were found at the time when the levels of both interleukins peak. The production of both IFN-γ and IL-4 by PHA-stimulated CD2+ lymphocytes from non-smouldering B-CLL patients was significantly higher than that from smouldering B-CLL patients while no significant differences were found in the production of IL-2, TNF-α, and TNF-β between the two B-CLL patient groups. These data suggest that functional alterations in the production of cytokines by CD2+ cells from B-CLL patients could help to explain the expansion of leukemic cells in B-CLL patients. Am. J. Hematol. 57:93–100, 1998. © 1998 Wiley-Liss, Inc.
Should inhaled anticholinergics be added to beta 2 agonists for treating acute childhood and adolescent asthma? A systematic review
Authors: L. H Plotnick, F. M Ducharme
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives</b> To estimate the therapeutic and adverse effects of addition of inhaled anticholinergics to β<sub>2</sub> agonists in acute asthma in children and adolescents. <b>Design</b> Systematic review of randomised controlled trials of children and adolescents taking β<sub>2</sub> agonists for acute asthma with or without the addition of inhaled anticholinergics. <b>Main outcome measures</b> Hospital admission, pulmonary function tests, number of nebulised treatments, relapse, and adverse effects. <b>Results</b> Of 37&nbsp;identified trials, 10&nbsp;were relevant and six of these were of high quality. The addition of a single dose of anticholinergic to β<sub>2</sub> agonist did not reduce hospital admission (relative risk 0.93,&nbsp;95% confidence interval 0.65&nbsp;to 1.32). However, significant group differences in lung function supporting the combination treatment were observed 60&nbsp;minutes (standardised mean difference −0.57, −0.93 to −0.21) and 120&nbsp;minutes (−0.53, −0.90 to −0.17) after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to β<sub>2</sub> agonists, mainly in children and adolescents with severe exacerbations, reduced the risk of hospital admission by 30% (relative risk 0.72, 0.53&nbsp;to 0.99). Eleven (95% confidence interval 5&nbsp;to 250) children would need to be treated to avoid one admission. A parallel improvement in lung function (standardised mean difference −0.66, −0.95 to −0.37) was noted 60&nbsp;minutes after the last combined inhalation. In the single study where anticholinergics were systematically added to every β<sub>2</sub> agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting, or tremor in patients treated with anticholinergics. <b>Conclusions</b> Adding multiple doses of anticholinergics to β<sub>2</sub> agonists seems safe, improves lung function, and may avoid hospital admission in 1&nbsp;of 11&nbsp;such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school aged children and adolescents with severe asthma exacerbation.