tbuckley/cabot-search huggingface dataset:
Hepatic adenine nucleotide metabolism measuredin vivo in rats fed ethanol and a high fat-low protein diet
Authors: Kei Miyamoto, Samuel W. French
Journal: Hepatology (1988)

Rats fed a diet high in fat and low in protein continuously infused by intragastric cannula were given ethanol for 2 to 6 months in order to examine the response of liver adenine nucleotides to changes in systemic PO 2 . Hepatic adenine nucleotides were measured in vivo monthly using liver obtained by biopsy from rats while a high blood alcohol level was maintained. Ethanol decreased hepatic ATP and the total adenylate pool, but did not change the levels of ADP and AMP. Adenylate energy charge showed only a tendency to be decreased. Carotid arterial PO 2 was mildly but significantly lower in ethanol-fed rats compared to the pair-fed controls. Pure O 2 inhalation for 3 min increased the PO 2 four times in the ethanol and control-fed rats, and tended to increase ATP and decrease ADP in ethanol-fed rats as well as pair-fed controls. It restored the energy charge to a normal level in the ethanol-fed rats. Ten per cent O 2 + 90% N 2 inhalation for 3 min decreased the PO 2 to 40 mm Hg in both the ethanol-fed and control rats, and this rapidly decreased ATP. This effect was significantly greater in the ethanol-fed rats compared to the controls. The total adenylate pool and the energy charge were decreased only in ethanol-fed rats. The results show that the reduced energy stores in the rat liver induced by ethanol are rapidly responsive to changes in PO 2 . Thus, the livers of ethanol-fed rats were more vulnerable to transient hypoxia than were controls.
Home-based deep breathing exercises after cardiac surgery - A randomized controlled trial
Authors: Elisabeth Westerdahl, Charlotte Urell, Marcus Jonsson, Ing-Liss Bryngelsson, Hans Hedenstrom, Margareta Emtner
Journal: European Respiratory Journal (2013)

Breathing exercises are recommended to cardiac surgery patients. Instructions concerning how long patients should continue exercises after discharge vary, and the significance of treatment needs to be determined. Our aim was to assess the effects of home-based deep breathing exercises performed with a positive expiratory pressure device for two months following cardiac surgery.

The study design was a prospective, single-blinded, parallel-group, randomized trial. Patients performing breathing exercises two months after cardiac surgery (n=159) were compared to a control group (n=154) performing no breathing exercises after discharge. The intervention consisted of 30 slow deep breaths performed with a positive expiratory pressure device (10-15 cmH20) five times a day during the first two months after surgery. The outcomes were lung function measurements, oxygen saturation, thoracic excursion mobility, subjective experiences of breathing and pain, patient-perceived quality of recovery, health-related quality of life and self-reported respiratory tract infection/pneumonia and antibiotic treatment.

Two months postoperatively, the patients had significantly reduced lung function, with a mean decrease in FEV1 to 93 ± 12 % (p <0.001) of preoperative values. Oxygenation had returned to preoperative values, and health-related quality of life was improved compared to preoperative values (p<0.01). There were no significant differences between the groups in any of the measured outcomes.

No significant differences in lung function, subjective experiences, or quality of life were found between patients performing home-based deep breathing exercises and control patients two months after cardiac surgery.
Phase III Multicenter Trial of Doxorubicin Plus Cyclophosphamide Followed by Paclitaxel Compared With Doxorubicin Plus Paclitaxel Followed by Weekly Paclitaxel As Adjuvant Therapy for Women With High-Risk Breast Cancer
Authors: David Loesch, F. Anthony Greco, Neil N. Senzer, Howard A. Burris, John D. Hainsworth, Stephen Jones, Svetislava J. Vukelja, John Sandbach, Frankie Holmes, Scot Sedlacek, John Pippen, Deborah Lindquist, Kristi McIntyre, Joanne L. Blum, Manuel R. Modiano, Kristi A. Boehm, Feng Zhan, Lina Asmar, Nicholas Robert
Journal: Journal of Clinical Oncology (2010)

This study compared disease-free survival (DFS) obtained with two different regimens of adjuvant therapy in high-risk breast cancer.Women (who had performance status [PS] of 0 to 1) with operable, histologically confirmed, stage I to III adenocarcinoma of the breast were eligible. Patients had undergone primary surgery with no residual tumor. Treatments were as follows: arm 1 was doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks for four cycles followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles (ie, AC-P); and arm 2 was doxorubicin 50 mg/m(2) plus paclitaxel 200 mg/m(2) every 3 weeks for four cycles followed by paclitaxel 80 mg/m(2) weekly for 12 weeks.Overall, 1,830 patients were enrolled and 1,801 were treated: arm 1 (n = 906; AC-->P) and arm 2 (n = 895; AP-WP). Overall, patients had a PS of 0 (88%), had estrogen receptor and progesterone receptor-positive disease (52%), had one to three positive nodes (46%), and were postmenopausal (57%); the median age was 52 years. Currently, 1,640 patients (90%) are alive. The 6-year DFS was 79% to 80% in both groups. Disease relapse was the cause of death for 83 patients in arm 1 and in 66 patients of arm 2. Overall 6-year survival rates were 82% and 87% in arms 1 and 2, respectively. Reasons for patients being taken off study treatment included toxicity (13% in arm 1 v 20% in arm 2), progressive disease or recurrence (7% v 5%), and consent withdrawn (9% v 8%), respectively. The most frequent toxicities were hematologic, including neutropenia and leukopenia followed by neuropathy, myalgia, nausea, fatigue, headache, arthralgia, and vomiting.The results indicate that the AP-WP regimen is an equally effective and tolerable option for the adjuvant treatment of patients with high-risk breast cancer. The substitution of paclitaxel for cyclophosphamide results in comparable effectiveness of the regimen.
Inhibition by antimicrotubular agents of the procoagulant activity generated by the blood monocytes: A biochemical and morphological study
Authors: Dominique de Prost, Elisabeth Cramer, Jacques Hakim
Journal: American Journal of Hematology (1979)

Abstract During in vitro incubation, human blood leukocytes triggered by various stimuli, generate and release procoagulant activity (PCA), which was identified as tissue factor‐like activity. The cell responsible for this production is the monocyte. Monocytes, when incubated in aseptic conditions generate and release PCA in the incubation medium, after a lag period of 1–2 hours. Most of the activity (95%) remains cell bound while only 5% are released. In order to ascertain whether microtubules (MT) act as an intermediate in the generation and/or the release of PCA, monocytes were incubated with antimicrotubular agents ie, colchicine or vinblastine. Both drugs inhibited PCA generation and release. Colchicine added after two hours of incubation was inhibitor after a lag period of one hour as expected by its delayed effectiveness on MT. The inhibition was more effective on the generation than on the release of PCA. Ultrastructural studies showed that both drugs significantly (P &lt; 0.01) disrupted microtubules while no modifications of the protein synthetizing apparatus or the lysosomes were observed. No accumulating material was seen inside the cells. These results suggest that colchicine or vinblastine act by their disrupting activity on MT, as inhibitors of PCA Generation by the monocytes. The decrease in PCA‐release would thus be secondary to a deficient generation of the activity. The absence of morphological modifications of the protein synthetizing apparatus suggest that antimicrotubular agents inhibit PCA synthesis by monocytes through the formation or transmission of the stimuli and not directly on the synthetizing sites.
Multimarker Approach to Evaluate the Incidence of the Metabolic Syndrome and Longitudinal Changes in Metabolic Risk Factors
Authors: Erik Ingelsson, Michael J. Pencina, Geoffrey H. Tofler, Emelia J. Benjamin, Katherine J. Lanier, Paul F. Jacques, Caroline S. Fox, James B. Meigs, Daniel Levy, Martin G. Larson, Jacob Selhub, Ralph B. D’Agostino, Thomas J. Wang, Ramachandran S. Vasan
Journal: Circulation (2007)

Background— The metabolic syndrome (MetS) is associated with increased cardiovascular risk. We evaluated the relative contributions of circulating biomarkers representing distinct biological pathways to the incidence of MetS and to longitudinal changes of its constituent risk factors. Methods and Results— We measured 8 circulating biomarkers reflecting inflammation (C-reactive protein), hemostasis (plasminogen activator inhibitor-1, fibrinogen), neurohormonal activity (aldosterone, renin, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide), and endothelial dysfunction (homocysteine) in 2292 Framingham Offspring Study participants (mean age, 57 years; 56% women). We related the biomarker panel to incidence of MetS on follow-up initially and then related biomarkers associated with incident MetS to longitudinal change in its components. On follow-up (mean, 2.9 years), 282 participants (of 1473 participants without prevalent MetS at baseline) developed MetS. After adjustment for clinical risk factors, the biomarker panel was associated with incident MetS ( P =0.008). On backward elimination, plasminogen activator inhibitor-1 and aldosterone remained associated with incident MetS (multivariable-adjusted odds ratio per 1-SD increment log marker, 1.31 [ P =0.004] and 1.21 [ P =0.015], respectively). In multivariable analyses evaluating longitudinal change in MetS components (analyzed as continuous variables), plasminogen activator inhibitor-1 was significantly and positively associated with changes in fasting glucose, systolic blood pressure, and triglycerides (all P &lt;0.05). Serum aldosterone was associated positively with change in systolic blood pressure ( P =0.023) and inversely with change in high-density lipoprotein cholesterol ( P =0.001). Conclusions— Higher circulating plasminogen activator inhibitor-1 and aldosterone levels are associated with the development of MetS and with longitudinal change of its components, suggesting that these biomarkers and related pathways play a key role in mediating metabolic risk.
A Randomized Controlled Trial of Peripheral Blood Mononuclear Cell Depletion in Experimental Human Lung Inflammation
Authors: Laura C. Barr, Mairi Brittan, Andrew Conway Morris, Daniel F. McAuley, Chiara McCormack, Alison M. Fletcher, Hamish Richardson, Martin Connell, Dilip Patel, William A. H. Wallace, Adriano G. Rossi, Donald J. Davidson, Lynn Manson, Marc Turner, Nikhil Hirani, Timothy S. Walsh, Niall H. Anderson, Kevin Dhaliwal, A. John Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Depletion of monocytes reduces LPS-induced lung inflammation in mice, suggesting monocytes as potential therapeutic targets in acute lung injury.To investigate whether depletion of circulating blood monocytes has beneficial effects on markers of systemic and pulmonary inflammation in a human model of acute lung inflammation.A total of 30 healthy volunteers were enrolled in a randomized controlled trial. Volunteers inhaled LPS at baseline, and were randomized to receive active mononuclear cell depletion by leukapheresis, or sham leukapheresis, in a double-blind fashion (15 volunteers per group). Serial blood counts were measured, bronchoalveolar lavage (BAL) was performed at 9 hours, and [(18)F]fluorodeoxyglucose positron emission tomography at 24 hours. The primary endpoint was the increment in circulating neutrophils at 8 hours.As expected, inhalation of LPS induced neutrophilia and an up-regulation of inflammatory mediators in the blood and lungs of all volunteers. There was no significant difference between the depletion and sham groups in the mean increment in blood neutrophil count at 8 hours (6.16 × 10(9)/L and 6.15 × 10(9)/L, respectively; P = 1.00). Furthermore, there were no significant differences in BAL neutrophils or protein, positron emission tomography-derived measures of global lung inflammation, or cytokine levels in plasma or BAL supernatant between the study groups. No serious adverse events occurred, and no symptoms were significantly different between the groups.These findings do not support a role for circulating human monocytes in the early recruitment of neutrophils during LPS-mediated acute lung inflammation in humans.
Applications of metabolomics for understanding the action of peroxisome proliferator-activated receptors (PPARs) in diabetes, obesity and cancer
Authors: Zsuzsanna Ament, Mojgan Masoodi, Julian L Griffin
Journal: Genome Medicine (2012)

The peroxisome proliferator-activated receptors (PPARs) are a set of three nuclear hormone receptors that together play a key role in regulating metabolism, particularly the switch between the fed and fasted state and the metabolic pathways involving fatty-acid oxidation and lipid metabolism. In addition, they have a number of important developmental and regulatory roles outside metabolism. The PPARs are also potent targets for treating type II diabetes, dyslipidemia and obesity, although a number of individual agonists have also been linked to unwanted side effects, and there is a complex relationship between the PPARs and the development of cancer. This review examines the part that metabolomics, including lipidomics, has played in elucidating the roles PPARs have in regulating systemic metabolism, as well as their role in aspects of drug-induced cancer and xenobiotic metabolism. These studies have defined the role PPARδ plays in regulating fatty-acid oxidation in adipose tissue and the interaction between aging and PPARα in the liver. The potential translational benefits of these approaches include widening the role of PPAR agonists and improved monitoring of drug efficacy.
Myoendothelial Coupling Is Not Prominent in Arterioles Within the Mouse Cremaster Microcirculation In Vivo
Authors: Daniel Siegl, Michael Koeppen, Stephanie E. Wölfle, Ulrich Pohl, Cor de Wit
Journal: Circulation Research (2005)

A smooth muscle hyperpolarization is essential for endothelium-dependent hyperpolarizing factor-mediated dilations. It is debated whether the hyperpolarization is induced by a factor (endothelium-derived hyperpolarizing factor) and/or is attributable to direct current transfer from the endothelium via myoendothelial gap junctions. Here, we measured membrane potential in endothelial cells (EC) and smooth muscle cells (SMC) in vivo at rest and during acetylcholine (ACh) application in the cremaster microcirculation of mice using sharp microelectrodes before and after application of specific blockers of Ca2+-dependent K+ channels (K(Ca)). Moreover, diameter changes in response to ACh were studied. Membrane potential at rest was lower in EC than SMC (-46.6+/-1.0 versus -36.5+/-1.0mV, P<0.05). Bolus application of ACh induced robust hyperpolarizations in EC and SMC, but the amplitude (11.1+/-0.9 versus 5.1+/-0.9mV, P<0.05) and duration of the response (10.7+/-0.8 versus 7.5+/-1.0s, P<0.05) were larger in EC. Blockers of large conductance K(Ca) (charybdotoxin or iberiotoxin) abrogated ACh-induced hyperpolarizations in SMC but did not alter endothelial hyperpolarizations. In contrast, apamin, a blocker of small conductance K(Ca) abolished ACh-induced hyperpolarizations in EC and had only small effects on SMC. ACh-induced dilations were strongly attenuated by iberiotoxin but only slightly by apamin. We conclude that myoendothelial coupling in arterioles in vivo in the murine cremaster is weak, as EC and SMC behaved electrically different. Small conductance K(Ca) mediate endothelial hyperpolarization in response to ACh, whereas large conductance K(Ca) are important in SMC. Because tight myoendothelial coupling was found in vitro in previous studies, we suggest that it is differentially regulated between vascular beds and/or by mechanisms acting in vivo.
What is good medicine?
Authors: Des Spence
Journal: BMJ (2012)

I write about bad medicine; not for the money, nor to be liked. I am not here to spread happiness, or insincere, sycophantic, doe eyed nonsense, but to counter what I see as the unrealistic, ill informed, pompous, overoptimistic ideas and practices that are pervasive in medicine. My remit is to blow some smoky realism into watering medical eyes. But I am no burnt out cynic, and I promised as penance to write about good medicine too. So many things spring to mind: vaccination, joint replacements, palliative care, anaesthesia, HIV …
High Prevalence of <i>BRCA1</i> and <i>BRCA2</i> Germline Mutations with Loss of Heterozygosity in a Series of Resected Pancreatic Adenocarcinoma and Other Neoplastic Lesions
Authors: Aimee L. Lucas, Reena Shakya, Marla D. Lipsyc, Elana B. Mitchel, Sheila Kumar, Caroline Hwang, Liyong Deng, Catherine Devoe, John A. Chabot, Matthias Szabolcs, Thomas Ludwig, Wendy K. Chung, Harold Frucht
Journal: Clinical Cancer Research (2013)

Pancreatic ductal adenocarcinoma (PDAC) is associated with the breast ovarian cancer syndrome (BRCA1/BRCA2) mutations. It is unknown if this association is causal.
Cognitive Deficit Induced by Acute Tryptophan Depletion in Patients With Alzheimer’s Disease
Authors: Richard J. Porter, Brian S. Lunn, Lucy L.M. Walker, John M. Gray, Clive G. Ballard, John T. O’Brien
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The study assessed the effects on global cognitive function and mood of a reduction of brain serotonin by means of acute tryptophan depletion in 16 patients with dementia of the Alzheimer type and in 16 cognitively intact comparison subjects. METHOD: In a double-blind, crossover design, subjects received a tryptophan-free amino acid drink to induce acute tryptophan depletion and, on a separate occasion, a placebo drink containing a balanced mixture of amino acids. On each occasion, ratings of depressed mood were made at baseline and 4 and 7 hours later, and the Modified Mini-Mental State was administered at baseline and 4 hours later. RESULTS: Patients with dementia of the Alzheimer type had a significantly lower mean score on the Modified Mini-Mental State after acute tryptophan depletion than after receiving placebo. The comparison group showed no difference in mean score on the Modified Mini-Mental State after acute tryptophan depletion and after receiving placebo. No significant changes in mood were found in either group. CONCLUSIONS: Acute tryptophan depletion significantly impaired cognitive function in patients with dementia of the Alzheimer type. Compromised serotonergic function, in combination with cholinergic deficit, may make an important contribution to cognitive decline in dementia of the Alzheimer type.
Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology
Authors: Alexis Arzimanoglou, Jacqueline French, Warren T Blume, J Helen Cross, Jan-Peter Ernst, Martha Feucht, Pierre Genton, Renzo Guerrini, Gerhard Kluger, John M Pellock, Emilio Perucca, James W Wheless
Journal: The Lancet Neurology (2008)
Prognostic significance of surface marker analysis in childhood non‐hodgkin's lymphoproliferative malignancies
Authors: Peter F. Coccia, John H. Kersey, Katamiera J. Gajl‐Peczalska, William Krivit, Mark E. Nesbit
Journal: American Journal of Hematology (1976)

Abstract Blast cell surface markers for T‐ and B‐lymphocyte characteristics were studied at diagnosis in 73 children with non‐Hodgkin's lymphoproliferative malignancies. Three distinctive groups of patients were identified on the basis of the analysis of blast cells for surface immunoglobulin (SIg), sheep erythrocyte (sE) rosette formation, and complement receptors. The seven group I patients had monoclonal IgM on their blast cells, morphologic features of Burkitt's lymphoma, abdominal masses, and very short survival. The 13 group II patients had receptors for sE, complement, or both on their blast cells, mediastinal or nodal masses, and short survival. The distinction between leukemia and lymphoma based on the presence of bone marrow involvement at diagnosis is not prognostically useful in this group of patients. The blast cells of group II patients could not be morphologically distinguished from those of the group III patients. The 53 group III patients had SIg, sE, and complement negative blast cells and could be further subdivided on the basis of white blood cell count. The nine group III A patients (&gt; 100.0 × 10 9 /liter) had in general short survival, while most of the 44 group III B patients (&lt; 100.0 × 10 9 /liter) have remained in complete remission. Positive surface markers, mass lesions, male sex, and age of diagnosis &lt; 2 years or ≧ 10 years appear to be interrelated factors indicating poor prognosis. Elevated white blood cell count is a prognostic indicator independent of surface marker analysis or presence of mass lesions.
Lung volume reduction effect after lobectomy in COPD patients
Authors: Alexey Petrunkin, Alexey Pichurov, Oleg Orzheshkovskiy, Piotr Yablonsky
Journal: European Respiratory Journal (2013)

Objectives: FEV1 is an important factor influencing on operability and life duration of COPD patients. Poor FEV1 is quite often cause for refusal to operate emphysematous patients.

Nevertheless recent studies affirmed lobectomy didn’t deteriorate FEV1 in some COPD patients.

Aim of the study is determination of factors influencing on PFT alteration after lobectomy.

Methods: 107 patients underwent lobectomy (53 nonCOPD, 18 – mild COPD, 24 – moderate, 12 - severe) were reassessed 6 – 12 moths postoperatively. There were male/female – 77/30, mean age – 62±2 years.

30 patients underwent right upper, 29 – left upper, 38 – lower and 10 – middle lobectomy.

ppoFEV1 was estimated by simple calculating of segments.

Results: There was no significant FEV1-loss in moderate to severe COPD patients after lobectomy. Predicted postoperative FEV1 (ppoFEV1) underestimated actual ones (apoFEV1) in these groups.

View this table:



Lower lobectomy led to minimal deterioration FEV1, other types resulted in significant FEV1-loss.

Conclusions: Lobectomy in patients with marked obstruction has lung volume reduction effect, which is maximal after lower lobectomy.

FEV1 increased from 57% till 60% postoperatively and was equal 135% of ppoFEV1 in 12 moderate to severe COPD patients underwent lower lobectomy and gave up smoking.
Adjuvant chemoradiation using 5-fluorouracil/folinic acid/cisplatin with or without paclitaxel and radiation in patients with completely resected high-risk gastric cancer: two cooperative phase II studies of the AIO/ARO/ACO
Authors: C. Kollmannsberger, W. Budach, M. Stahl, N. Schleucher, T. Hehr, H. Wilke, J. Schleicher, U. Vanhoefer, E.C. Jehle, K. Oechsle, T. Trarbach, I. Boehlke, L. Kanz, J.T. Hartmann, C. Bokemeyer
Journal: Annals of Oncology (2005)