tbuckley/cabot-search huggingface dataset:
Electrical Activity of the Diaphragm during Pressure Support Ventilation in Acute Respiratory Failure
Authors: JENNIFER BECK, STEWART B. GOTTFRIED, PAOLO NAVALESI, YOANNA SKROBIK, NORMAN COMTOIS, MAURO ROSSINI, CHRISTER SINDERBY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We compared crural diaphragm electrical activity (EAdi) with transdiaphragmatic pressure (Pdi) during varying levels of pressure support ventilation (PS) in 13 intubated patients. With changing PS, we found no evidence for changes in neuromechanical coupling of the diaphragm. From lowest to highest PS (2 cm H(2)O +/- 4 to 20 cm H(2)O +/- 7), tidal volume increased from 430 ml +/- 180 to 527 ml +/- 180 (p < 0.001). The inspiratory volume calculated during the period when EAdi increased to its peak did not change from 276 +/- 147 to 277 +/- 162 ml, p = 0.976. Respiratory rate decreased from 23.9 (+/- 7) to 21.3 (+/- 7) breaths/min (p = 0.015). EAdi and Pdi decreased proportionally by adding PS (r = 0.84 and r = 0.90, for mean and peak values, respectively). Mean and peak EAdi decreased (p < 0.001) by 33 +/- 21% (mean +/- SD) and 37 +/- 23% with the addition of 10 cm H(2)O of PS, similar to the decrease in the mean and peak Pdi (p < 0.001) observed (34 +/- 36 and 35 +/- 23%). We also found that ventilator assist continued during the diaphragm deactivation period, a phenomenon that was further exaggerated at higher PS levels. We conclude that EAdi is a valid measurement of neural drive to the diaphragm in acute respiratory failure.
Three-dimensional observations of the hepatic arterial terminations in rat, hamster and human liver by scanning electron microscopy of microvascular casts
Authors: Kazuhide Yamamoto, Igor Sherman, James M. Phillips, Murray M. Fisher
Journal: Hepatology (1985)

The arterial terminations were studied by scanning electron microscopy of microvascular casts in rat, hamster and human livers. Important species differences were observed. In the rat, frequent anastomoses between the terminal hepatic arterioles and portal venules were observed, whereas a few arterioles terminated directly into sinusoids. On the contrary, no arterioportal venous anastomoses were demonstrated in the hamster and human livers. In these latter species, all arterioles terminated into sinusoids adjacent to the portal tracts. No intralobular arterioles were observed in any species.
Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease
Authors: Bernard De Bruyne, William F. Fearon, Nico H.J. Pijls, Emanuele Barbato, Pim Tonino, Zsolt Piroth, Nikola Jagic, Sven Mobius-Winckler, Gilles Rioufol, Nils Witt, Petr Kala, Philip MacCarthy, Thomas Engström, Keith Oldroyd, Kreton Mavromatis, Ganesh Manoharan, Peter Verlee, Ole Frobert, Nick Curzen, Jane B. Johnson, Andreas Limacher, Eveline Nüesch, Peter Jüni
Journal: New England Journal of Medicine (2014)

We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).
Exertion injuries in female athletes.
Authors: S. Orava, A. Hulkko, E. Jormakka
Journal: British Journal of Sports Medicine (1981)

Because sports injuries in men form most of the available statistics, the reportage of injuries in female athletes is sparse. We describe exertion injuries and disorders in 281 women athletes, all of which hampered athletic training or performances. Sixty per cent of the injuries occurred to girls ages between 12-19 years, and about forty-eight per cent were track and field athletes. The most common sites of injury were the ankle, foot, heel and leg. Osteochondritic disorders were the most typical injuries in the series, and the chronic medical tibial syndrome was the injury that needed surgical treatment most frequently. Overuse injuries seem to differ very little from each other in the events included in this survey.
The Role of Eosinophil Activation in Preterm Infants with Bronchopulmonary Dysplasia
Authors: S. Choi, Y. Rha
Journal: Journal of Allergy and Clinical Immunology (2011)

RATIONALE: Bronchopulmonary dysplasia (BPD) results in bronchial hyperresponsiveness and recurrent wheezing. Recent studies suggested that eosinophil has relevance to innate immune defense and inflammatory process in early life. While the activation of neutrophil and macrophage in pathogenesis of BPD are rather well studied, very few studies have addressed the possible participation of eosinophil. We hypothesized that eosinophil may be involved in early phase of BPD. METHODS: Preterm infants were recruited consecutively and grouped to respiratory distress syndrome (RDS) or non-RDS. RDS group was divided to BPD or non-BPD group then. We investigated blood eosinophil, serum eosinophil cationic protein (ECP), eosinophil protein X (EPX), and urine EPX to determine the relationship between eosinophil activation and BPD in premature infants prospectively. The eosinophil count, serum ECP/ EPX and urine ECP/ EPX were compared. Spearman rank test was used to analyze the correlation between serum, tracheal and urine ECP. RESULTS: Among total 43 patients recruited, 13 patients were treated with pulmonary surfactant and mechanical ventilation for RDS. Six out of 13 patients were diagnosed with BPD. There were no difference of blood eosinophil, serum ECP, EPX, or urine EPX between RDS and non-RDS groups. Blood eosinophil, serum ECP, EPX, and urine EPX were higher in BPD group than non-BPD group which was not statistically significant. Interestingly serum EPX was significantly correlated with pH of arterial blood gas analysis which was done at discharge. (r=0.441, p=0.012) CONCLUSIONS: Eosinophil activation markers were higher in BPD group which suggests the possible role of eosinophil in BPD although there was no statistical significance.
Beneficial Effects of Insulin Versus Sulphonylurea on Insulin Secretion and Metabolic Control in Recently Diagnosed Type 2 Diabetic Patients
Authors: Michael Alvarsson, Göran Sundkvist, Ibe Lager, Marianne Henricsson, Kerstin Berntorp, Eva Fernqvist-Forbes, Lars Steen, Gunilla Westermark, Per Westermark, Thomas Örn, Valdemar Grill
Journal: Diabetes Care (2003)

To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment.Beta-cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment.After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 +/- 0.08 nmol/l, whereas it was decreased by 0.12 +/- 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA(1c) levels decreased significantly during the first year in both groups; however, at the end of the second year, HbA(1c) had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA(1c) during the second year was significant between groups, P < 0.02. A questionnaire indicated no difference in well-being related to treatment.Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.
Increased p21<sup>CIP1/WAF1</sup>and B Cell Lymphoma Leukemia-x<sub>L</sub>Expression and Reduced Apoptosis in Alveolar Macrophages from Smokers
Authors: Katsuyuki Tomita, Gaetano Caramori, Sam Lim, Kazuhiro Ito, Toyoyuki Hanazawa, Timothy Oates, Irena Chiselita, Elen Jazrawi, K. Fan Chung, Peter J. Barnes, Ian M. Adcock
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Alveolar macrophages (AMs) are the predominant defense cells in the airway, and their numbers are increased in smokers and subjects with chronic obstructive pulmonary disease. This increase may result from increased recruitment, increased proliferation, or reduced cell death. Apoptosis regulates inflammatory cell survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle progression after oxidative stress. We have investigated whether chronic smoke exposure influences the expression and localization of cell cycle and apoptotic proteins in AM and bronchial epithelial cells in vivo. The increased numbers of AMs seen in smokers were only partially due to enhanced proliferation. p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm. In addition, B cell lymphoma leukemia (Bcl)-x(L), an antiapoptotic regulator, was also highly expressed in macrophages from smokers compared with nonsmokers and subjects with asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of p21(CIP1/WAF1) and failed to induce apoptosis in an in vitro model. These results suggested that AM and bronchial epithelial cells from smokers, in contrast to those from normal subjects and subjects with asthma, have reduced cell death. Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis.
THE EFFECTS OF SOME COMPOUNDS ON THE ENDOGENOUS RESPIRATION OF SKIN
Authors: V. J. W. LONG, H. J. YARDLEY
Journal: British Journal of Dermatology (1971)

SUMMARY.— The effects of 2-bromostearic acid, 2: 4-dinitrophenol and menadione on the respiration of skin slices in the presence or absence of added glucose was measured. All 3 compounds depress endogeneous respiration, whereas in the presence of added substrate, 2-bromostearic acid has no effect and 2: 4-dinitrophenol and menadione stimulate respiration. Since cells in the upper part of the epidermis are in a giucose-free environment, it is suggested that in vitro tests of potentially toxic substances should be performed both in the presence and in the absence of glucose.
What Constitutes “Improved Prognosis”?
Authors: George P. Canellos
Journal: Journal of Clinical Oncology (2008)

The article, "Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high-dose methotrexate alternating with standard agents (M-BACOD)," 1 describes one of several multidrug regimens that were conceived in the 1970s after the demonstration that combination chemotherapy was capable of curing patients with what was then called diffuse histiocytic/undifferentiated lymphoma and now is better known-after multiple classifications-as diffuse large B cell (or T cell) lymphoma.The era of this publication generally preceded immunophenotypic markers.The therapeutic era for combination chemotherapy in diffuse large cell lymphoma, in fact, was launched with the demonstration by the National Cancer Institute (NCI) Bethesda group that cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), a variant of the chemotherapy nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) regimen for Hodgkin's lymphoma, could induce long-term diseasefree survival, which was tantamount to cure. 2 In the 1970s, a number of regimens referred to in the discussion were emerging, and all were showing good results in uncontrolled phase II trials.This was the era of cyclophosphamide, vincristine, methotrexate, leucovorin, cytarabine (COMLA; Yale), bleomycin, doxorubicin, cyclophosphamide, vincristine, prednisone (BACOP; NCI), methotrexate, leucovorin, doxorubicin, cyclophosphamide, vincristine, bleomycin, prednisone (MACOP-B; Vancouver), prednisone, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate, leucovorin (PRO-MACE-MOPP or CYTO-BOM; NCI), Lymphome non-Hodgkin-80 (Groupe d'Etude des Lymphomes de l'Adulte), and indeed cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; Southwest Oncology Group). [3]4][5][6][7][8] However, the 1970s and early 1980s were devoid of the histochemical and molecular tools available today for prognostic determinants in diffuse large cell lymphoma.The only exception was probably serum lactic dehydrogenase.The M-BACOD regimen was designed to incorporate high-dose methotrexate with folinic acid rescue during the phase (day 14) of bone marrow suppression secondary to doxorubicin, cyclophosphamide, and vincristine, which were given on day 1 every 21 days for six cycles.The therapeutic lessons of that era are still with us, except that now there is the nonmyelotoxic antiCD20 antibody, rituximab, added to CHOP (CHOP-R) that is the current standard, having been shown to be superior to CHOP alone. 9-11That era taught us, however, the value and need for prospective randomized trials as opposed to institutional phase II trials.The first lesson was to distinguish single-institution trials from cooperative group trials, where the influence of selection bias is less in the latter.
Incidence of peripheral neuropathy in high-risk early-stage breast cancer patients receiving dose-dense paclitaxel in central Pennsylvania
Authors: A. C. Barochia, L. Cream, H. Harvey, J. Sivik
Journal: Journal of Clinical Oncology (2009)

e11595 Background: Paclitaxel (P) is an important part of chemotherapy regimens for early breast cancer. Breast cancer survivors may be left with iaotrogenic peripheral neuropathy which can affect their quality of life. Methods: We conducted a retrospective, IRB approved, medical chart review to determine the rate of peripheral neuropathy in a tertiary care practice in central Pennsylvania. Patients had biopsy proven, newly diagnosed, high risk breast cancer. Patients were treated with a standard dose dense (DD) regimen where 4 cycles of adriamycin (A) 60 mg/m2/cyclophosphamide (C) 600 mg/m2 were followed by four cycles of paclitaxel (P) 175 mg/m2 every 2 weeks (Citron et al) between 7/2006 to7/2008 at Penn State Cancer Institute. All patients who received dose dense chemotherapy by a single provider were included (n=23). No peripheral neuropathy (PN) was reported before initiating paclitaxel, but 3 of 23 patients had type II diabetes. Electronic medical charts were reviewed and data was abstracted to analyze incidence of peripheral neuropathy. These data were compared to reported published data. Results: 22 pts received dose dense AC followed by P chemotherapy. 100% completed 4 cycles of AC and 87% complete 4 cycles of P. Overall, 82% developed neuropathy (32% with grade 1, 41 % with grade 2, 9 % with grade 3). Almost 30% of patients required gabapentin for control of neuropathic pain. 35% of patients with PN had symptoms persisting &gt;3 months after chemotherapy. Conclusions: A considerable percentage of high risk, early breast cancer patients treated with AC followed by DD paclitaxel developed at least mild neurotoxicity. Rates of Grade 3 neurotoxicity were much higher (9%) than the previous CALGB-9741 study (4%). This may be related to regional pharmacogenomic differences. Although dense dose paclitaxel has been shown to improve disease free survival, PN affects most patients treated with paclitaxel and for some patients can have a prolonged impact on their quality of life. Future studies should attempt identify which patients are at risk for severe peripheral neuropathy. No significant financial relationships to disclose.
International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors
Authors: M. D. Hollenberg
Journal: Pharmacological Reviews (2002)

Proteinase-activated receptors (PARs) represent a unique subclass of G-protein-coupled receptors of which four family members have now been cloned from a number of species. The novel mechanism of receptor activation involves the proteolytic unmasking of a cryptic N-terminal receptor sequence that, remaining tethered, binds to and triggers receptor function. In addition, short (five to six amino acids) synthetic peptides, based on the proteolytically revealed motif, can activate PARs without the unmasking of the tethered ligand. This article summarizes the experiments leading to the pharmacological characterization and cloning of the four PAR family members and provides a rationale for their designation by the acronym "PAR". The ability to distinguish among the PARs pharmacologically 1) with selective proteinase activators, 2) with receptor-selective peptide agonists, and 3) with peptide and nonpeptide antagonists is discussed, as are the molecular mechanisms of receptor activation and desensitization/internalization. Finally, the potential physiological roles of the PARs, which are widely distributed in many organs in the settings of tissue injury, repair, and remodeling, including embryogenesis and oncogenesis are discussed, and the newly appreciated roles of proteinases as signaling molecules that can act as either functional agonists or antagonists are highlighted.
Absorption and Transport of Digitoxin in the Dog
Authors: G. Charles Oliver, John Cooksey, Charles Witte, Marlys Witte
Journal: Circulation Research (1971)

Absorption of digitoxin as its studied in 14 fasted anesthetized dogs after administration of 50 µc of 3 H-digitoxin mixed with 1 mg of unlabeled digitoxin into either the duodenum or stomach. Radioactivity was measured in portal, hepatic, and central venous plasma, thoracic duct lymph, common duct bile and urine for 5 hours after digitoxin was given. Three dogs were given a single intravenous dose of 25 µc of 3 H-digitoxin mixed with 0.5 mg of unlabeled digitoxin, and radioactivity was measured in central venous plasma and thoracic duct lymph. Digitoxin was absorbed rapidly and uniformly from the duodenum and entered the body entirely by way of the portal vein, reaching peak concentrations in portal blood in 1 to 15 minutes. Digitoxin was absorbed erratically from the stomach. No metabolites of digitoxin were observed in selected portal venous samples subjected to thin-layer chromatography. Absorption of orally administered digitoxin into the systemic bloodstream is retarded because of highly efficient hepatic extraction of the drug and subsequent transfer into bile.
Flow–function relations during graded coronary occlusions in the dog: effects of transmural location and segment orientation
Authors: A McCulloch
Journal: Cardiovascular Research (1998)

Objective: The sensitive relationship between regional myocardial perfusion and local systolic deformation during acute myocardial ischemia is not independent of the transmural location or segment orientation. The aim of this study was to determine the effects of fiber orientation and transmural location on the relationships between regional myocardial flow and three-dimensional systolic wall strain during graded coronary artery occlusions. Methods: Transmural distributions of three-dimensional strain (by biplane radiography of implanted radiopaque markers) and myocardial blood flows (using fluorescent microspheres) were measured in the ischemic region during graded left anterior descending (LAD) coronary artery occlusions in 12 anesthetized dogs. Results: Occlusion of the coronary artery did not significantly alter mean heart rate or end-systolic pressure. As flow decreased during graded occlusions, ischemia significantly changed systolic circumferential, longitudinal, radial, fiber and cross-fiber strains (p<0.004). There was a significant effect of transmural position on circumferential, cross-fiber and radial strains, but not on fiber or longitudinal strains. Ischemia significantly altered all normal strains: circumferential, longitudinal, fiber, cross-fiber and radial. There was a strong interaction effect between transmural location and blood flow for circumferential, cross-fiber and radial strains, but not fiber or longitudinal strains. Conclusion: During non-transmural ischemia, there is evidence of strong transmural tethering in the cross-fiber direction, whereas the fiber-strain flow relation is independent of transmural position. Thus, whether the relationship between local myocardial bloodflow and systolic strain during acute ischemia is dependent on transmural location, depends on segment orientation.