tbuckley/cabot-search huggingface dataset:
ANEMIA AND HYPOPROTEINEMIA
Authors: L. L. Miller, F. S. Robscheit-Robbins, G. H. Whipple
Journal: The Journal of Experimental Medicine (1947)

Dogs with sustained anemia and hypoproteinemia due to bleeding and a continuing low protein or protein-free diet with abundant iron are used to test the value of food proteins as contrasted with mixtures of pure amino acids. The stimulus of double depletion (anemia and hypoproteinemia) drives the body to use every source of protein and all protein-building materials with the utmost conservation. Raiding of body tissue protein to produce plasma protein and hemoglobin is a factor when protein-building factors are supplied in small amounts. In this severe test (double depletion) the good food proteins in adequate amounts are able to maintain body weight, a strongly positive nitrogen balance, and produce considerable amounts of new hemoglobin and plasma protein. Casein, lactalbumin, whole egg protein, liver protein are all adequate in amounts of 150 to 250 gm. protein per week. Under comparable conditions mixtures of pure amino acids (essential for growth) do produce large amounts of new hemoglobin and plasma protein and a positive nitrogen balance but do not maintain body weight. The loss of weight is conspicuous even with large amounts of amino acids (200 to 300 gm. protein equivalent per week). Methionine, threonine, and phenylalanine are related to nitrogen conservation in growth mixtures of essential amino acids (Paper I) but when these three are given together they have little influence on the doubly depleted dog (Table 3). Some unidentified substance or compound present in certain proteins but absent in mixtures of the essential amino acids may be responsible for these differences in the response of the doubly depleted dog.
Respiratory symptoms, atopy and bronchial hyperreactivity in professional firefighters
Authors: D. Miedinger, P. N. Chhajed, D. Stolz, C. Gysin, A-B. Wanzenried, C. Schindler, C. Surber, H. C. Bucher, M. Tamm, J. D. Leuppi
Journal: European Respiratory Journal (2007)

The aim of the present study was to assess respiratory health in professional firefighters. A total of 101 male professional firefighters from Basel, Switzerland, were included in the study. A control group consisting of 735 male subjects of the general population was composed of the Basel sample of the Swiss Study on Air Pollution and Lung Diseases in Adults. All subjects were administered a standardised questionnaire, spirometry, skin-prick tests and bronchial challenge testing to methacholine. Respiratory symptoms at work were more frequent in firefighters compared with the control group, including burning eyes (21 versus 3%), running nose (19 versus 2%), itchy throat (26 versus 3%), cough (28 versus 3%), dyspnoea (7 versus 2%) and headache (25 versus 3%), respectively. Atopy was present in 51% of firefighters compared with 32% in the control group. The odds ratio for hyperreactivity to methacholine was 2.24 (95% confidence interval 1.12–4.48) for firefighters compared with the control group. Firefighters reported more respiratory symptoms at work and suffered more often from atopy compared with the control group. Bronchial hyperreactivity was more pronounced in firefighters, but it was not related to acute exposure or duration of employment. It remains unclear whether these findings were present at recruitment or developed after joining the workforce.
Randomized Multicenter Phase II Trial Comparing Two Schedules of Etirinotecan Pegol (NKTR-102) in Women With Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer
Authors: Ignace B. Vergote, Agustin Garcia, John Micha, Charles Pippitt, Johanna Bendell, Daniel Spitz, Nicholas Reed, Graham Dark, Paula M. Fracasso, Emad N. Ibrahim, Vincent A. Armenio, Linda Duska, Chris Poole, Christine Gennigens, Luc Y. Dirix, Abraham C.F. Leung, Carol Zhao, Raoudha Soufi-Mahjoubi, Gordon Rustin
Journal: Journal of Clinical Oncology (2013)

Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma.
Global Climate Controversy
Authors: S. F. Singer
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Readers of JAMA deserve a balanced account on whether global warming (because of increases in greenhouse gases) will be good or bad for human health. The article by Dr Patz and colleagues<sup>1</sup>fails to do this. First, dealing with climate science, the article presents ice core data of carbon dioxide (CO<sub>2</sub>) and temperature for the last 180 000 years (Figure 1) and notes the close correlation, implying that past increases of CO<sub>2</sub>have led to strong warming and that the current increase will do the same. This is misleading. Readers should be warned that the compressed time scale (100000 years per inch) cannot show the cases where temperature increases preceded the CO<sub>2</sub>increases. Nevertheless, one can discern a CO<sub>2</sub>increase 125 000 years ago associated with a drop in temperature. Figure 1 in the article shows a dramatic (projected) doubling of CO<sub>2</sub>, but the
Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration
Authors: Ching-Hon Pui, Jun J. Yang, Stephen P. Hunger, Rob Pieters, Martin Schrappe, Andrea Biondi, Ajay Vora, André Baruchel, Lewis B. Silverman, Kjeld Schmiegelow, Gabriele Escherich, Keizo Horibe, Yves C.M. Benoit, Shai Izraeli, Allen Eng Juh Yeoh, Der-Cherng Liang, James R. Downing, William E. Evans, Mary V. Relling, Charles G. Mullighan
Journal: Journal of Clinical Oncology (2015)

To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups.With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia chromosome-like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL.The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.
Treatment of Travelers' Diarrhea: Ciprofloxacin plus Loperamide Compared with Ciprofloxacin Alone
Authors: David N. Taylor, Jose L. Sanchez, William Candler, Scott Thornton, Charles McQueen, Peter Echeverria
Journal: Annals of Internal Medicine (1991)

To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea.Double-blind, placebo-controlled, randomized clinical trial.United States Army hospital in Egypt.United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded.All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo.Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common.After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19).In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe.
Histopathologic and Immunohistochemical Characterization of Rash to Human Epidermal Growth Factor Receptor 1 (HER1) and HER1/2 Inhibitors in Cancer Patients
Authors: Beatrice Nardone, Kimberly Nicholson, Marissa Newman, Joan Guitart, Pedram Gerami, Nicholas Talarico, Ximing J. Yang, Alfred Rademaker, Dennis P. West, Mario E. Lacouture
Journal: Clinical Cancer Research (2010)

Human epidermal growth factor receptor (HER) 1 and HER 1/2 inhibitors have shown benefit against a wide range of solid tumors. However, their use is associated with rash in 40% to 90% of patients, which impacts quality of life and interrupts antineoplastic therapy. The pathologic characteristics of affected skin remain unclear, precluding development of rational therapies. The aim of this study was to evaluate differences in histologic and immunohistochemical alterations in rash caused by lapatinib, a dual HER1/2 inhibitor (HER1/2i), and the single HER1 inhibitors (HER1i) cetuximab, erlotinib, and panitumumab.For each of the four drugs, skin biopsies were collected and analyzed from 8 patients with rash (n = 32). Blinded independent histologic analysis and automated measurement of 17 skin biomarkers involved in proliferation, differentiation, and inflammation were conducted.Increased expression of pAKT and decreased dermal K16 and p27 for HER1/2i when compared with each of the HER1i were observed. In addition, decreased epidermal atrophy and follicular neutrophilic infiltrate were evidenced in the skin of patients on HER1/2i when compared with HER1i.We found a lower inhibition of epidermal kinetics and decreased inflammation in HER1/2i-induced rash. These findings underscore differences in skin toxicity as related to specificity of HER blockade, concordant with clinical tolerability and decreased severity of skin toxicity seen with the HER1/2i lapatinib compared with the HER1 inhibitors cetuximab, erlotinib, and panitumumab.
Modeling the Tumor Growth Profiles in Xenograft Experiments—Response
Authors: Lili Zhao, Meredith A. Morgan, Leslie A. Parsels, Jonathan Maybaum, Theodore S. Lawrence, Daniel Normolle
Journal: Clinical Cancer Research (2011)

We would like to thank Dr. Bassukas and Dr. Heitjan ([1][1]) for their comments about our work. Dr. Bassukas has raised the concern that tumor growth or regression, approximated by an exponential function over time, does not yield biologically relevant information. He suggests that sigmoid curves (
Anionic polypeptide fraction in bile of patients with and without gallstones
Authors: Nicole Domingo, Huguette Lafont, Zamir Halpern, Yohanan Peled, Jean Grosclaude, Tuvia Gilat
Journal: Hepatology (1993)

With the demonstration of pronucleating and antinucleating proteins, the role of biliary proteins became of considerable research interest. Anionic polypeptide fraction is the third most abundant biliary protein; it is found in association with biliary lipids, has antinucleating properties for calcium and is found in gallstones. Its levels in various human biles have not been studied as of this writing. In this investigation the concentration of anionic polypeptide fraction in gallbladder bile was measured in 16 subjects without gallstones, 19 subjects with cholesterol stones and 15 subjects with pigment stones in Tel Aviv. Anionic polypeptide fraction concentrations in bile (mean ± S.D.) were 0.76 ± 0.09 gm/L in controls and 0.81 ± 0.25 gm/L (which was not significant) in patients with cholesterol gallstones. They were significantly higher 1.03 ± 0.23 (p < 0.05) in patients with pigment gallstones. The anionic polypeptide fraction/phospholipid ratio and the anionic polypeptide fraction/total lipid ratio were significantly higher in patients with pigment gallstones (p < 0.005 and 0.05, respectively). The anionic polypeptide fraction lipid ratios were insignificantly elevated in biles of patients with cholesterol stones compared with the ratios in biles of controls. Only the anionic polypeptide fraction/phospholipid ratio was significantly higher in biles of patients with pigment stones compared with those with cholesterol gallstones. The values were similar although higher in a small group of gallstone patients from Marseilles. The role of anionic polypeptide fraction in the pathogenesis of gallstones, particularly pigment gallstones, requires further study. (HEPATOLOGY 1993;17:778–780.)
IGF-Binding Protein-3 Modulates TGF-β/BMP-Signaling in Glomerular Podocytes
Authors: Imke Peters, Irini Tossidou, Johannes Achenbach, Robert Woroniecki, Michael Mengel, Joon-Keun Park, Melanie Paschy, Kirsten de Groot, Hermann Haller, Mario Schiffer
Journal: Journal of the American Society of Nephrology (2006)

Podocyte apoptosis initiates progressive glomerulosclerosis in TGF-β1 transgenic and CD2AP-knockout (CD2AP−/−) mice. It was previously shown that in both mouse models, activation of the TGF-β pathway is the key event during development of podocyte apoptosis. Furthermore, CD2AP is an important modifier of TGF-β–induced survival signaling via activation of the phosphoinositol 3-kinase/AKT signaling pathway. This article presents IGF-binding protein-3 (IGFBP-3) as a new modulator of apoptosis and survival signaling in glomerular podocytes. High expression of IGFBP-3 protein in the urine of diseased CD2AP−/− mice was discovered, and IGFBP-3 expression in glomerular podocytes and parietal cells was detected. IGFBP-3 can induce changes in podocyte actin cytoskeleton, leads to apoptosis in cultured murine podocytes, and can enhance TGF-β1–induced apoptosis in vitro. For studying this process on a molecular level, proapoptotic p38 mitogen-activated protein kinase pathways and antiapoptotic phosphoinositol 3-kinase/AKT pathways were examined in cultured murine podocytes. It was found that IGFBP-3 increments the level of TGF-β1–induced phosphorylated p38 mitogen-activated protein kinase and decreases the phosphorylation of antiapoptotic AKT. This effect is specific for the co-stimulation of IGFBP-3 with TGF-β1 because a combination of IGFBP-3 with bone morphogenic protein-7 (BMP-7), another member of the TGF-β superfamily, results in apoptosis opposing signaling effects with a strong increase of phosphorylated AKT and subsequent functional effects. These results demonstrate that the IGF/IGFBP axis plays an important role in the development of podocyte apoptosis by modulation of TGF-β and BMP-7–induced pro- and antiapoptotic signals.
A free lung health check for the European Parliament: Healthy Lungs for Life
Authors: Marine Faure
Journal: European Respiratory Journal (2015)

Marcel Proust, the celebrated early twentieth century French writer, suffered from severe bronchial asthma his entire life, eventually succumbing to pneumonia. In 1900, he wrote: “ An attack of asthma of unbelievable violence and tenacity – such is the depressing balance sheet of my night, which it obliged me to spend on my feet in spite of the early hour at which I got up yesterday .” In the twenty first century, 600 000 Europeans continue to die prematurely from lung diseases [1]. Asthma, chronic obstructive respiratory disease (COPD), lung cancer, pulmonary hypertension and other respiratory diseases are, in combination, responsible for one in eight deaths in the 28 countries of the European Union [1]. When they do not result in death, they may harshly affect the life of the individuals or become a heavy economic burden for society. Hospital costs, treatments and loss of productivity, due to a patient's inability to work and premature death, are estimated at more than €380 billion [1]. ERS and ELF are committed to raising awareness on the importance of lung health among EU policy makers <http://ow.ly/JV3nD>
Glucocorticoid therapy increases COX-2 gene expression in nasal polyps in vivo
Authors: L. Pujols, P. Benitez, I. Alobid, A. Martinez-Antón, J. Roca-Ferrer, J. Mullol, C. Picado
Journal: European Respiratory Journal (2008)

The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal polyps. In total, 65 patients with nasal polyps were randomly (3:1) treated with (n = 51; 33 with asthma) or without (n = 14) oral prednisone and intranasal budesonide for 2 weeks plus intranasal budesonide for 10 additional weeks. Biopsies were obtained at baseline and after 2 and 12 weeks of treatment. All samples were analysed for cyclooxygenase-1 and cyclooxygenase-2 mRNA. Attempts were made to detect cyclooxygenase-2 protein. At baseline, cyclooxygenase-1 and cyclooxygenase-2 expression did not differ between polyps from nonasthmatic and asthmatic patients. Cyclooxygenase-1 mRNA was unchanged by glucocorticoid treatment, while cyclooxygenase-2 mRNA increased in glucocorticoid-treated patients at week 2 compared with baseline and then decreased at week 12. Within subgroups, increased cyclooxygenase-2 mRNA was found at week 2 in polyps from nonasthmatic and asthmatic patients compared with baseline. At week 12, cyclooxygenase-2 expression remained high in nonasthmatics while it decreased in asthmatics. Cyclooxygenase-2 protein was not detected under any circumstances. Glucocorticoid therapy enhances cyclooxygenase-2 expression in vivo in nasal polyps, a finding that does not follow the generally accepted assumption that cyclooxygenase-2 expression is suppressed by glucocorticoids.
Clinical Lectures ON KIDNEY PAIN
Authors: E. H. Fenwick
Journal: BMJ (1911)

of rheumatic fever, came to the hospital for pain and swelling of the left breast.The swelling had lasted a week, and there was tenderness and some hardness on examination.This sym- ptom rapidly disappeared with the aid of mild aperients and warm applications.CASE Il.Anne M., aged 10 years, was under me at 7 suffering from rheumatism, with arthritis, chorea, and endocarditis.She made a good recovery, and had kept apparently free from any relapse.Eer mother now brought her for pain, tenderness, swelling, and hardness of the left breast.There was definite evidence of her previous attack of rheumatism in an enlarged heart and a double mitral murmur.Her temperature was not raised, and the condition rapidly subsided.CASE III.Florence M., aged 13 years, had been under my observation
Enhancement of the Antitumor Effects of 1,3-Bis(2-Chloroethyl)-1-Nitrosourea and Cyclophosphamide by Vitamin A&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Martin H. Cohen, Paul P. Carbone
Journal: JNCI Journal of the National Cancer Institute (1972)

Vitamin A alcohol enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to a considerable extent and of cyclophosphamide to a lesser degree in murine L1210 leukemia. Enhancement was maximal when vitamin A alcohol was given parenterally 3–6 hours before the carcinostatic agent. The observed enhancement was somewhat specific for the nitrosoureas, since less effect was seen when other alkylating agents and antimetabolites were studied. Direct observation of leukemic cells and ancillary experiments on red blood cells suggest that enhancement was secondary to a vitamin A-BCNU interaction within tumor cell membranes, leading to irreversible and lethal membrane alterations. The doses of vitamin A used appear tolerable for humans.
Early Changes in Energy Metabolism in the Myocardium Following Acute Coronary Artery Occlusion in Anesthetized Dogs
Authors: WOLFGANG BRAASCH, SIGMUNDUR GUDBJARNASON, PRITPAL S. PURI, KURT G. RAVENS, RICHARD J. BING
Journal: Circulation Research (1968)

The tissue content of energy-rich phosphates and glycolytic metabolites and the activity of myocardial enzymes were examined in the dog after producing myocardial infarction by ligating branches of the anterior descending and circumflex coronary arteries. The pattern of systolic fiber movement shown by a strain-gauge assembly differentiated ischemic from nonischemic portions of myocardium. In ischemic muscle, 30 minutes after onset of ischemia, creatine phosphate content fell from 8.0 to 1.4 µmoles/g, ATP content fell from 5.8 to 1.5 µmoles/g, lactate content rose tenfold, and α-glycerophosphate content rose fivefold. The content of energy-rich phosphates and glycolytic metabolites did not change much in nonischemic muscle. The activities of myocardial enzymes were assayed in extracts of tissue samples from ischemic and nonischemic muscle 5 to 120 minutes after coronary artery occlusion. The activities of aldolase, lactic dehydrogenase (LDH), glyceraldehydephosphate dehydrogenase, α-glycerophosphate dehydrogenase, malate dehydrogenase (MDH), and 6-phosphogluconate dehydrogenase did not change significantly in ischemic muscle during 2 hours of observation. In nonischemic muscle, phosphofructokinase activity increased 75% 5 minutes after coronary occlusion, followed by an increase in activity of isocitrate dehydrogenase, creatinephosphokinase, MDH, and LDH. The enzymatic changes in nonischemic muscle suggest metabolic changes in nonischemic muscle accompanying compensatory hyperfunction and increased energy requirements of surviving muscle.
Recurrent Cystitis and Bladder Mass in Two Adults with Chronic Granulomatous Disease
Authors: Frederick S. Southwick
Journal: Annals of Internal Medicine (1988)

Two men, aged 23 and 20 years, with recurrent episodes of severe cystitis and X-linked chronic granulomatous disease were studied. Ultrasonography showed large discrete bladder masses that mimicked bladder carcinoma in both patients. Urine and bladder biopsy cultures were negative and histopathologic findings were consistent with chronic inflammation. One patient improved with symptomatic therapy on two occasions; the other patient required prolonged intravenous antibiotic therapy before fever and dysuria resolved. The possible mechanisms by which such inflammatory bladder masses might arise are discussed and eight previously reported cases of chronic granulomatous disease with cystitis are reviewed. From this clinical experience, we recommend prolonged antibiotic therapy. In patients who fail to respond to antibiotic therapy, steroids may be cautiously administered.