tbuckley/cabot-search huggingface dataset:
Effects of Prone Positioning on Lung Protection in Patients with Acute Respiratory Distress Syndrome
Authors: Rodrigo A. Cornejo, Juan C. Díaz, Eduardo A. Tobar, Alejandro R. Bruhn, Cristobal A. Ramos, Roberto A. González, Claudia A. Repetto, Carlos M. Romero, Luis R. Gálvez, Osvaldo Llanos, Daniel H. Arellano, Wilson R. Neira, Gonzalo A. Díaz, Aníbal J. Zamorano, Gonzalo L. Pereira
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Positive end-expiratory pressure (PEEP) and prone positioning may induce lung recruitment and affect alveolar dynamics in acute respiratory distress syndrome (ARDS). Whether there is interdependence between the effects of PEEP and prone positioning on these variables is unknown.To determine the effects of high PEEP and prone positioning on lung recruitment, cyclic recruitment/derecruitment, and tidal hyperinflation and how these effects are influenced by lung recruitability.Mechanically ventilated patients (Vt 6 ml/kg ideal body weight) underwent whole-lung computed tomography (CT) during breath-holding sessions at airway pressures of 5, 15, and 45 cm H2O and Cine-CTs on a fixed thoracic transverse slice at PEEP 5 and 15 cm H2O. CT images were repeated in supine and prone positioning. A recruitment maneuver at 45 cm H2O was performed before each PEEP change. Lung recruitability was defined as the difference in percentage of nonaerated tissue between 5 and 45 cm H2O. Cyclic recruitment/de-recruitment and tidal hyperinflation were determined as tidal changes in percentage of nonaerated and hyperinflated tissue, respectively.Twenty-four patients with ARDS were included. Increasing PEEP from 5 to 15 cm H2O decreased nonaerated tissue (501 ± 201 to 322 ± 132 grams; P < 0.001) and increased tidal-hyperinflation (0.41 ± 0.26 to 0.57 ± 0.30%; P = 0.004) in supine. Prone positioning further decreased nonaerated tissue (322 ± 132 to 290 ± 141 grams; P = 0.028) and reduced tidal hyperinflation observed at PEEP 15 in supine patients (0.57 ± 0.30 to 0.41 ± 0.22%). Cyclic recruitment/de-recruitment only decreased when high PEEP and prone positioning were applied together (4.1 ± 1.9 to 2.9 ± 0.9%; P = 0.003), particularly in patients with high lung recruitability.Prone positioning enhances lung recruitment and decreases alveolar instability and hyperinflation observed at high PEEP in patients with ARDS.
Reduced Expression of Hypoxia-Inducible Factor-1α in Perinecrotic Regions of Solid Tumors
Authors: Solmaz Sobhanifar, Christina Aquino-Parsons, Eric J. Stanbridge, Peggy Olive
Journal: Cancer Research (2005)

Hypoxia that develops in solid tumors stabilizes the hypoxia-inducible factor-1alpha (HIF-1alpha) subunit of the HIF-1 transcription factor, leading to up-regulation of dozens of hypoxia-regulated genes that increase glycolysis and oxygen delivery. HIF-1alpha and its downstream target gene CA9 have both been used as surrogate hypoxia markers, and, in general, high expression predicts for a poor response to treatment. Combinations of hypoxia markers offer the opportunity to measure changes in tumor oxygenation that may be relevant to tumor response to treatment. We compared the degree of colocalization of two endogenous markers for hypoxia, HIF-1alpha and carbonic anhydrase IX (CAIX), with a chemical marker for hypoxia, pimonidazole. Unexpectedly, expression of HIF-1alpha was reduced in the most hypoxic regions that border necrosis in xenograft tumors composed of SiHa cervical carcinoma, WiDr colon carcinoma, or M006 astrocytoma cells. Similar results were obtained for samples from three cervical cancer biopsies. However, CAIX was present in these perinecrotic cells that were also capable of metabolizing and binding a chemical marker for hypoxia, pimonidazole. In vitro experiments using tumor cells and tumor cubes incubated under anoxic conditions indicated that nutrient deprivation seems to be largely responsible for the lack of HIF-1alpha expression in perinecrotic regions. The half-life of CAIX was sufficiently long that, once formed, it remained for days in the absence of continued HIF-1alpha expression. These results have implications for the use of HIF-1alpha as an indicator of tumor hypoxia and aggressiveness as well as development of hypoxia-directed antitumor therapies based on the expression of HIF-1alpha.
IL-17–Mediated M1/M2 Macrophage Alteration Contributes to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws
Authors: Qunzhou Zhang, Ikiru Atsuta, Shiyu Liu, Chider Chen, Shihong Shi, Songtao Shi, Anh D. Le
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Osteonecrosis of the jaw (ONJ) is emerging as one of the important complications in cancer patients treated with antiresorptive agents. This study explored the potential role of interleukin (IL)-17–mediated M1/M2 macrophage alterations in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Experimental Design: The expression of IL-17 and M1 and M2 macrophage markers at the local mucosal site of human BRONJ lesions was examined by immunofluorescence studies. BRONJ-like disease was induced in C57BL/6 mice and multiple myeloma-burdened mice by intravenous injection of zoledronate to evaluate the correlation of elevated IL-17 levels with changes in M1 and M2 macrophage phenotypes and the therapeutic effects of blocking IL-17 on pathogenesis of BRONJ-like disease. Results: Increased T-helper (TH)17 cells and IL-17 cytokine correlate with an increase in M1/M2 macrophages ratio at the local mucosal site of both murine and human BRONJ lesion. Convincingly, in mice burdened with multiple myeloma, a combination of elevated suprabasal level and drug-induced IL-17 activity augmented the incidence of BRONJ; both systemic increase of IL-17 and disease severity could be reversed by adoptive transfer of ex vivo expanded M2 macrophages. Targeting IL-17 via specific neutralizing antibodies or a small inhibitory molecule, laquinimod, significantly decreased M1/M2 ratio and concomitantly suppressed BRONJ-like condition in mice. Mechanistically, IL-17 enhanced IFN-γ–induced M1 polarization through augmenting STAT-1 phosphorylation while suppressing IL-4–mediated M2 conversion via inhibiting STAT-6 activation. Conclusions: These findings have established a compelling linkage between activated IL-17–mediated polarization of M1 macrophages and the development of BRONJ-like conditions in both human disease and murine models. Clin Cancer Res; 19(12); 3176–88. ©2013 AACR.
Serum Transferrin Receptor
Authors: J. D. Cook, B. S. Skikne, R. D. Baynes
Journal: Annual Review of Medicine (1993)

The transferrin receptor plays a critical role in iron metabolism by precisely contrOlling the flow of transferrin iron into body cells. A soluble truncated form of the receptor can be detected in human serum using sensitive immunoassays, and the initial clinical experience with this new measurement indicates that it reflects the total body mass of tissue receptor. Serum receptor levels rise significantly with tissue iron deficiency and the heightened demand for iron associated with expansion of the erythroid marrow. The serum receptor provides a quantitative measure of functional iron deficiency and distinguishes the associated anemia from that of chronic disease. If iron deficiency is excluded, the serum receptor provides a quantitative measure of total erythropoiesis that is more sensitive and less invasive than bone marrow examination currently used to assess red cell precursor mass. Performed in conjunction with serum ferritin measurements, the serum receptor will be useful in establishing the true prevalence of iron deficiency anemia in population studies.
Scaling up oral rehydration salts and zinc for the treatment of diarrhoea
Authors: O. Sabot, K. Schroder, G. Yamey, D. Montagu
Journal: BMJ (2012)

Is cheap and effective and could accelerate reductions in child mortality

In the years after the launch of the millennium development goals, the health economist Jeffrey Sachs emphasised investment in malaria control as the “lowest hanging fruit” in the battle to reduce child mortality.1 Such investment is paying off: cases of malaria and deaths from the disease, which mostly occur in young children, have fallen by more than 50% in nine African countries since 2000 through scaling up of malaria control tools.2 Yet despite this progress in controlling malaria and in scaling up other interventions such as vaccines, most countries are still not on track to achieve millennium development goal 4—that of reducing child mortality by two thirds from 1990 to 2015. With only four years until the deadline, we must now pursue other “low hanging fruit” that can rapidly reduce child mortality in developing countries.

Investment in the treatment of diarrhoea with oral rehydration salts (ORS) plus zinc is one of the best opportunities to achieve such rapid impact.3 Acute diarrhoea is the second biggest cause of death in children worldwide, causing 1.2 million deaths each year.4 Rotavirus vaccines, clean water, sanitation, and other preventive measures are important in reducing this burden. However, vaccines are only partially …
Nuclear magnetic resonance studies on the structure and function of rhodopsin
Authors: Steven O. Smith
Journal: Behavioral and Brain Sciences (1995)

Abstract Magic angle spinning (MAS) NMR methods provide a means of obtaining high resolution structural data on rhodopsin and its photoin termediates. Current work has focused on the structure of the retinal chromophore and its interactions with surrounding protein charges. The recent development of MAS NMR methods for measuring internuclear distances with a resolution of ∼0.2 will complement diffraction methods for addressing key mechanistic questions.
Paclitaxel, Not Bevacizumab, Was Primarily Responsible for the Favorable Effects Seen in the RIBBON-2 Trial
Authors: Altug Kesikli, Saadettin Kilickap
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: The article by Brufsky et al 1 discusses the efficacy and safety of the application of bevacizumab in combination with standard chemotherapy protocols in patients with human epidermal growth factor receptor 2‐negative breast cancers, as a secondline treatment in metastatic settings. 1 The authors suggest that the addition of bevacizumab to standard chemotherapy regimens improved progression-free survival (PFS) and objective response rates. Inaddition,theauthorsreportthatbevacizumabcouldsafelybeused, despite adverse effects such as the increased risk of hypertension and proteinuria. Although the addition of bevacizumab to standard chemotherapy in this study 1 improved PFS, the improvement was more prominent with taxane combinations than with other chemotherapy regimens. Moreover, theresults from subgroup analyses suggest that paclitaxel was primarily responsible for the favorable effects seen when it was used in combination with bevacizumab. Indeed, it has beendemonstratedpreviouslythatpaclitaxelinhibitangiogenesisand tumormetastasis. 2 Hence,paclitaxelisknowntohavebothantiangio
Shall I compare thee to a... Big game animal? Ship? World Cup football team? Navigator on a foggy night? Car? Spice? Breakfast cereal?
Authors: I. Loefler, I. Loefler, M. Marusic, C. R Cleaveland, J. Howells, K. Abbasi, A. Searle
Journal: BMJ (1998)

# Shall I compare thee to a… {#article-title-2}

The five largest general medical journals like to refer to themselves as “the big five.” This reminded Nairobi surgeon Imre Loefler of Africa's five big game animals, and he set about exploring the similarities in more detail. Next came ships. Given the opportunity for harmless fun and the chance to exact public revenge, we thought that other people might like to play this game, so we invited entries from visitors to our website (and one or two others). To Loefler's big game animals and ships were added cars, football teams, and Spice Girls. Taken together, they probably say more about the wellsprings of the male imagination than about medical journals. The game need not end here—submit your five-pack using the “rapid response” option on our website. 

# Big game animal? {#article-title-3}

I am well acquainted with both the big five medical journals and the big five game animals, having spent much time in their company. I have learnt from them, I cherish and admire them, and I appreciate the differences in their character. Why not match the two groups in pairs since animals have always been used as symbols for institutions?

   ![][1] 

Watch out! Like the elephant JAMA is a poor converter of food

JAMA is undoubtedly the elephant, and not only because of its size. It is dominant and loud, ranging over a huge territory, within which, however, it commutes on well trodden paths. It can do a lot of damage by pushing, shoving, and trampling, and ultimately it can devastate its own environment. It is a poor converter of food, and many other species thrive on its droppings. It has stamina, it is gregarious and supportive, and it has the wisdom of the conservative kind. It has a good memory. It revisits fruiting trees regularly. It can survive drought by adapting to meagre food …

 [1]: /embed/graphic-1.gif
MOTORING MATTERS FOR MEDICAL MEN: SOME PHASES OF THE LIGHT CAR PROBLEM
Authors: H. M. Buist
Journal: BMJ (1914)

best sense of the word never existed.He was tlhe autlhor of Elements of Physics, whlich withlin 'a lewx years was translated into every language of civilized Europe.He founded sclholarslhips for experimental plhysics not only in his own Alna Mater, but ill the otlher universities of Scotland, anud in the Uniiversity of London, to the Senate of wlhiclh he was nominated on its foundation.
Peripheral Blood Stem Cell and Bone Marrow Transplantation for Solid Tumors and Lymphomas: Hematologic Recovery and Costs: A Randomized, Controlled Trial
Authors: Olivier Hartmann
Journal: Annals of Internal Medicine (1997)

Background: Previous studies have suggested that peripheral blood stem cell (PBC) transplantation has an advantage over autologous bone marrow transplantation. Objective: To compare the hematologic recovery and costs associated with PBC transplantation with those associated with autologous bone marrow transplantation in patients receiving high-dose chemotherapy for solid tumors or lymphomas. Design: Multicenter, randomized, controlled clinical trial. Setting: French Federation of Cancer Centers, located in cancer facilities or public hospitals with transplantation units. Patients: Children and adults with solid tumors or lymphomas who were candidates for high-dose chemotherapy. Interventions: Bone marrow or filgrastim-mobilized PBCs. Measurement: The major end point was the duration of thrombocytopenia (platelet count < 50 × 109/L). An economic evaluation of both types of transplantation was done prospectively to measure costs and cost-effectiveness. Results: 129 patients entered the trial; 64 had PBC transplantation, and 65 had bone marrow transplantation. The median duration of thrombocytopenia was 16 days in the PBC group and 36 days in the bone marrow group (P < 0.001). All of the other clinical end points studied (time to last platelet transfusion, duration of granulocytopenia, number of transfusion episodes, and duration of hospitalization) favored PBC transplantation. A cost analysis showed that total cost was decreased by 17% in adults and 29% in children with PBC transplantation; thus, PBC transplantation was clearly more cost-effective than bone marrow transplantation for both platelet and granulocyte recovery. Conclusion: Transplantation of PBCs is associated with more rapid hematologic recovery than is bone marrow transplantation after high-dose chemotherapy for solid tumors or lymphomas. Furthermore, global costs are lower and cost-effectiveness ratios are better with PBC transplantation.
Effects of a Beta-Receptor Blocking Agent (Propranolol) on Synthesis of IgE in vitro by Peripheral Blood Lymphocytes from Atopic Patients
Authors: Anders Hovmark, Eva ÅSbrink
Journal: Allergy (1981)

Peripheral blood lymphocytes from patients with atopy were studied for IgE production in vitro. Addition of a beta-receptor blocking agent (propranolol) to lymphocytes from 9 of 10 patients with low spontaneous IgE production in vitro caused increased IgE production. In 10 tests with lymphocytes from patients, who were undergoing hyposensitization treatment for cat epithelium and/or birch pollen allergy, no spontaneous in vitro production of the relevant antigen-specific IgE antibodies was detected. However, when propranolol was added to the lymphocyte cultures in vitro, production of antigen-specific IgE antibodies was found. No such production was found when lymphocytes from patients who were not allergic to either of these antigens were studied. Szentivanyi's theory of a partial blockade of beta-adrenergic receptors in atopy and a possible linkage between this theory and the hypotheses of disturbed regulatory functions in the immune system of patients with atopy is discussed.
Evaluation of the trophic effect of longterm treatment with the histamine H2 receptor antagonist loxtidine on rat oxyntic mucosa by differential counting of dispersed cells.
Authors: E Brenna, H G Swarts, C H Klaassen, J J de Pont, H L Waldum
Journal: Gut (1994)

To evaluate whether the general trophic effect of gastrin on the oxyntic mucosa is an indirect effect mediated by histamine H2 receptors, sustained 24 hour hypergastrinaemia was induced in Sprague-Dawley rats by treatment with the long acting and potent histamine H2 antagonist loxtidine for five months. The trophic effect was assessed by weight, enumeration of total mucosal cells, parietal cells, and enterochromaffin like cells in smears stained for the actual cells after enzymatic dispersion of the mucosa, and by biochemical analysis of oxyntic mucosal homogenates. The weight of the whole stomach and the oxyntic mucosa increased by 12.7% (p = 0.016) and 27.5% (p = 0.006), respectively. Total oxyntic mucosal protein content increased by 28.7% (p = 0.058). Total numbers of mucosal cells and parietal cells increased by 11.9% (NS) and 24.1% (NS), respectively. The amount of the parietal cell specific enzyme H+,K(+)-ATPase was unchanged. On the other hand, the number of enterochromaffin like cells and related parameters, histidine decarboxylase activity and histamine content of the oxyntic mucosa, showed a pronounced and significant increase. It is concluded that the general trophic effect of gastrin on the oxyntic mucosa is not mediated by the histamine H2 receptor. The tropic effect of gastrin on the parietal cell seems, in contrast with that on the enterochromaffin like cell, not to be specific but only reflecting the general trophic effect on the oxyntic mucosa.