tbuckley/cabot-search huggingface dataset:
Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer.
Authors: F Oshita, K Noda, Y Nishiwaki, A Fujita, Y Kurita, T Nakabayashi, K Tobise, S Abe, S Suzuki, I Hayashi, Y Kawakami, T Matsuda, S Tsuchiya, S Takahashi, T Tamura, N Saijo
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the effects of irinotecan (CPT-11) given in combination with etoposide (VP-16) in metastatic non-small-cell lung cancer (NSCLC), to evaluate response and survival rates, and to determine the qualitative and quantitative toxicities of the combination chemotherapy. PATIENTS AND METHODS Sixty-one metastatic NSCLC patients received concurrent administration of CPT-11 and VP-16 for 3 days with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support. RESULTS Fifty-nine patients were assessable for response and all 61 patients were assessable for toxicity and survival. Fifty-six patients were treated with two or more courses of chemotherapy. Thirteen patients achieved a partial response (PR), 36 showed no change (NC), and 10 showed progressive disease (PD). The overall response rate was 21.3% (95% confidence interval, 12.9% to 33.1%). The median duration of PRs was 141 days (range, 62 to 299). Of the hematologic toxicities, 14 (23%) and 24 (39%) patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. The toxicities were feasible. Treatment-related death occurred in one patient who suffered hypovolemic shock induced by hematemesis. The median survival time was 10.0 months and the 1-year survival rate was 36.1%. CONCLUSION Combination chemotherapy with concurrent administration of CPT-11 and VP-16 with rhG-CSF support was only modestly effective against metastatic NSCLC, with feasible toxicities of moderate diarrhea and pulmonary toxicity. The results were equivalent to those expected with either cisplatin-based chemotherapy or with CPT-11 alone.
Extracellular matrix remodelling in the endometrium and its possible relevance to the pathogenesis of endometriosis
Authors: M Sillem, S Prifti, M Neher, B Runnebaum
Journal: Human Reproduction Update (1998)

Essential features of endometrial physiology involve the extracellular matrix (ECM). In the pathogenesis of endometriosis, interactions of endometriosis cells with ECM can be postulated. Two systems of secreted proteases in the endometrium, the plasmin(ogen) activator/inhibitor and the matrix metalloproteinases and their inhibitors were examined in cell cultures of uterine endometrial cells from women with and without endometriosis. Soluble urokinase receptor secretion is increased, and mRNA transcription of tissue inhibitor of metalloproteinases-2 (TIMP-2) is upregulated by progestin in endometriosis. These findings are compatible with an altered ECM turnover in the endometrium of these patients that may explain a higher invasive potential of retrogradely menstruated endometrial fragments.
35 GENOTYPIC CHARACTERISATION OF FILIBUVIR (PF-00868554) RESISTANCE IN PATIENTS RECEIVING FOUR WEEKS CO-ADMINISTRATION OF FILIBUVIR WITH PEGIFN/RBV (12 WEEK ANALYSIS)
Authors: J. Mori, J.L. Hammond, S. Srinivasan, S. Jagannatha, E. van der Ryst
Journal: Journal of Hepatology (2010)
THE PUBLIC HEALTH ASPECTS OF COMPLEX EMERGENCIES AND REFUGEE SITUATIONS
Authors: MJ Toole, RJ Waldman
Journal: Annual Review of Public Health (1997)

▪ Abstract Populations affected by armed conflict have experienced severe public health consequences mediated by population displacement, food scarcity, and the collapse of basic health services, giving rise to the term complex humanitarian emergencies. These public health effects have been most severe in underdeveloped countries in Africa, Asia, and Latin America. Refugees and internally displaced persons have experienced high mortality rates during the period immediately following their migration. In Africa, crude mortality rates have been as high as 80 times baseline rates. The most common causes of death have been diarrheal diseases, measles, acute respiratory infections, and malaria. High prevalences of acute malnutrition have contributed to high case fatality rates. In conflict-affected European countries, such as the former Yugoslavia, Georgia, Azerbaijan, and Chechnya, war-related injuries have been the most common cause of death among civilian populations; however, increased incidence of communicable diseases, neonatal health problems, and nutritional deficiencies (especially among the elderly) have been documented. The most effective measures to prevent mortality and morbidity in complex emergencies include protection from violence; the provision of adequate food rations, clean water and sanitation; diarrheal disease control; measles immunization; maternal and child health care, including the case management of common endemic communicable diseases; and selective feeding programs, when indicated.
Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma
Authors: Paul Gerard Guy Richardson, Bart Barlogie, James Berenson, Seema Singhal, Sundar Jagannath, David Irwin, S. Vincent Rajkumar, Teru Hideshima, Hugh Xiao, Dixie Esseltine, David Schenkein, Kenneth C. Anderson
Journal: Blood (2005)
Increased vascular expression of iNOS at day but not at night in asthmatic subjects with increased nocturnal airway obstruction
Authors: N.H.T. ten Hacken, D.S. Postma, G. Drok, M. Smith, J Kraan, W Timens
Journal: European Respiratory Journal (2000)

Nitric oxide production by endothelial cells may have important consequences for the development of airway inflammation as well as for airway obstruction. The present study investigated whether the expression of vascular inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in human bronchi differs between asthmatic and healthy subjects, and whether it shows a circadian rhythm, especially in subjects with increased nocturnal airway obstruction. Bronchial biopsy samples were taken at 16:00 and 04:00 h from 13 healthy and 25 asthmatic subjects, 18-45 yrs. Biopsy samples were snap-frozen and double-immunostained for iNOS and eNOS in combination with a common vascular antigen (CD31). The degree of immunopositivity was expressed as a percentage of CD31-positive vessels encountered in complete biopsy sections. Asthmatic subjects showed greater iNOS expression than healthy controls: 23+/-15 versus 7+/-17% (mean+/-SD) at 16:00 h (p&lt;0.001) and 19+/-15 versus 8+/-11% at 04:00 h (p&lt;0.05). Asthmatic subjects with a fall in forced expiratory volume in one second of &gt;10% of the predicted value between 16:00 and 04:00 h showed greater iNOS expression at 16:00 than at 04:00 h: 32+/-16 versus 20+/-13% (p&lt;0.05). eNOS expression did not differ between healthy controls and asthmatic patients, nor did it differ between 16:00 and 04:00 h. It is suggested that asthmatic subjects with increased nocturnal airway obstruction demonstrate increased activation of inducible nitric oxide synthase during the day. The resulting nitric oxide production might protect against airway obstruction during the day. However, at night, nitric oxide production is probably insufficient to counterbalance the bronchoconstricting forces.
Does negative expiratory pressure influence performances of spirometry in older patients?
Authors: D. Vanpee, Ch. Swine, J.P. Delwiche, J. Jamart, L. Delaunois
Journal: European Respiratory Journal (2002)

The aim of this study is to assess the influence of the negative expiratory pressure (NEP) technique on the performance of maximal expiratory manoeuvre in elderly patients. Firstly, the authors studied how NEP (at 5 and 10 cmH2O, NEP5 and NEP10) influences forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 60 young healthy volunteers, in order to assess the fluctuations of the method. In the second part of the study, 65 successive elderly inpatients (>70 yrs old) were examined. In this group, 15 elderly patients were unable to perform the manoeuvre, 27 had a normal function, 14 had a lung function with obstructive pattern and nine with restrictive pattern. In young subjects, FVC during NEP5 and NEP10 compared to baseline values was 101+/-5%, and 103+/-5%, respectively, and FEV1 was 100+/-4% and 101+/-5%, respectively. In elderly patients with normal function, FVC during NEP5 and NEP10 compared to baseline values was 99+/-14% and 109+/-23%, respectively, and FEV1 was 97+/-9% and 104+/-13%, respectively. There were no relevant effects of the NEP application on FVC or FEV1 values in elderly patients with an obstructive or restrictive pattern. In elderly patients, the use of the negative expiratory pressure technique during maximal expiratory manoeuvres provides little complementary information compared to a classical manoeuvre. The negative expiratory pressure technique did not modify the initial diagnosis when compared with the classical manoeuvre.
Body Fluid Dynamics
Authors: Gautam Bhave, Eric G. Neilson
Journal: Journal of the American Society of Nephrology (2011)

Pioneering investigations conducted over a half century ago on tonicity, transcapillary fluid exchange, and the distribution of water and solute serve as a foundation for understanding the physiology of body fluid spaces. With passage of time, however, some of these concepts have lost their connectivity to more contemporary information. Here we examine the physical forces determining the compartmentalization of body fluid and its movement across capillary and cell membrane barriers, drawing particular attention to the interstitium operating as a dynamic interface for water and solute distribution rather than as a static reservoir. Newer work now supports an evolving model of body fluid dynamics that integrates exchangeable Na+ stores and transcapillary dynamics with advances in interstitial matrix biology.
Control of Renal Solute Excretion by Enteric Signals and Mediators
Authors: Leslie Thomas, Rajiv Kumar
Journal: Journal of the American Society of Nephrology (2008)

Renal solute excretion is important for the homeostasis of various ions. It is widely believed that hormones such as aldosterone, parathyroid hormone, the vitamin D endocrine system, and growth factors are responsible for alterations in renal ion transport in response to increased absorption of enteric solutes. In the cases of sodium, potassium, and phosphorus, moieties produced in the gastrointestinal tract alter renal ion transport when foods that have high concentrations of cognate ions are ingested. The gastrointestinal tract senses the presence of increased luminal concentrations of these ions, presumably via specific "sensors," and responds by releasing effector substances into the intestinal wall and portal circulation. These substances rapidly increase renal excretion or reduce renal tubular reabsorption and thus blunt large increases in the serum concentrations of these ions. The characterization of enteric solute sensors and mediators will greatly advance our understanding of physiologic mechanisms that control solute homeostasis and will allow the development of specific drugs that stimulate or inhibit these pathways.
Novel Biopolymers to Enhance Endothelialisation of Intra‐vascular Devices
Authors: Salvatore Pernagallo, Olga Tura, Mei Wu, Kay Samuel, Juan J. Diaz‐Mochon, Anna Hansen, Rong Zhang, Melany Jackson, Gareth J. Padfield, Patrick W.F. Hadoke, Nicholas L. Mills, Marc L. Turner, John P. Iredale, David C. Hay, Mark Bradley
Journal: Advanced Healthcare Materials (2012)

Rapid endothelisation is of critical importance in the prevention of adverse remodelling after device implantation. Currently, there is a need for alternative strategies to promote re-endothelialisation for intravascular stents and vascular grafts. Using polymer microarray technology 345 polymers are comprehensively assessed and a matrix is identified that specifically supports both progenitor and mature endothelial cell activity in vitro and in vivo while minimising platelet attachment. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: Effects on primary bile acids in babies and mothers
Authors: G Mazzella
Journal: Hepatology (2001)

Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA) treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients were given UDCA at 1.5 to 2 g/d, to our knowledge the highest dosage yet reported. Effects were evaluated on conjugated bile acids (BA) in amniotic fluid (15 of 20 patients) and umbilical cord serum obtained at delivery (20 of 22 newborns), as compared with 10 untreated patients (amniotic fluid, 9 of 10 patients; cord serum, 9 of 10 newborns). Liver function tests, serum BA and UDCA were evaluated on enrollment and then weekly until 1 week after delivery. Maternal serum conjugated cholic (CCA) and chenodeoxycholic (CCDCA) acids levels fell (18.5 ± 1.9 to 10.5 ± 1.9 μmol/L, and 5.8 ± 0.8 to 2.97 ± 0.7 μmol/L, respectively [P < .01]) in treated patients, and remained unaffected (20.0 ± 3.1 vs. 20.3 ± 2.3, and 5.6 ± 0.6 vs. 5.4 ± 0.5, respectively [P = not significant]) in untreated ones. Serum conjugated UDCA levels rose to 16.5 ± 1.8 μmol/L (P < .001). Median values of CCA and CCDCA in amniotic fluid around delivery were 4.9 ± 12.4 and 4.8 ± 7.7 μmol/L, respectively, in treated patients, as against 17.9 ± 27.5 and 18.5 ± 20.9 μmol/L in untreated ones. In treated mothers, CCA and CCDCA concentrations in cord blood were 6.0 ± 0.9 and 5.2 ± 0.95 μmol/L, respectively, as against 21.9 ± 5.6 and 18.9 ± 2.1 μmol/L in untreated ones. In treated patients, median UDCA values in amniotic fluid and cord blood were 0.8 ± 2.4 and 0.9 ± 0.14 μmol/L, respectively. We conclude that increasing the dose of UDCA more effectively controls ICP and improves maternal clinical outcome after delivery.
DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies
Authors: Iiris Hovatta, Matthew A Zapala, Ron S Broide, Eric E Schadt, Ondrej Libiger, Nicholas J Schork, David J Lockhart, Carrolee Barlow
Journal: Genome biology (2007)

Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies, expression profiles were derived from either homogenized whole brain or collections of large brain regions. However, the brain is a very heterogeneous organ, and expression profiles of different brain regions vary significantly. Because of the importance and potential power of eQTL studies in identifying regulatory networks, we analyzed gene expression patterns in different brain regions from multiple inbred mouse strains and investigated the implications for the design and analysis of eQTL studies. Gene expression profiles of five brain regions in six inbred mouse strains were studied. Few genes exhibited a significant strain-specific expression pattern, whereas a large number of genes exhibited brain region-specific patterns. We constructed phylogenetic trees based on the expression relationships between the strains and compared them with a DNA-level relationship tree. The trees based on the expression of strain-specific genes were constant across brain regions and mirrored DNA-level variation. However, the trees based on region-specific genes exhibited a different set of strain relationships, depending on the brain region. An eQTL analysis showed enrichment of cis-acting regulators among strain-specific genes, whereas brain region-specific genes appear to be mainly regulated by trans-acting elements. Our results suggest that many regulatory networks are highly brain region specific and indicate the importance of conducting eQTL mapping studies using data from brain regions or tissues that are physiologically and phenotypically relevant to the trait of interest.
A phase III, randomized placebo-controlled trial of the safety and efficacy of d-MPH as new treatment of fatigue and “chemobrain” in adult cancer patients
Authors: E. Lower, S. Fleishman, A. Cooper, J. Zeldis, H. Faleck, D. Manning
Journal: Journal of Clinical Oncology (2005)

8000 Background: This study investigated the safety and efficacy of dexmethylphenidate (d-MPH, Focalin) in the treatment of persistent fatigue and memory impairment after chemotherapy in non-anemic cancer patients. Methods: Adult patients (primary or metastatic brain tumors excluded) treated with ≥4 cycles of cytotoxic chemotherapy (completed ≥2 months prior to entry) were eligible. Patients completing a single-blind placebo period with no symptomatic improvement were randomized to an 8-week double-blind phase. Dosing (d-MPH or placebo) was adjusted from 10 to 50 mg/day and maintained for ≥2 weeks. Efficacy endpoints were change from Baseline (last observation carried forward) in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F) Total Score (primary) and High Sensitivity Cognitive Screen (HSCS) Overall Total and Subscale Scores (secondary). Planned accrual was 160 to obtain 120 completed patients, based on comparison of FACIT-F scores in the 2 groups, assuming a 2-sided test with Type 1 error rate of 0.05, 80% power, mean FACIT-F scores of 36.8 (placebo) and 31.4 (d-MPH), and a common standard deviation of 10.5. Results: Overall, 152 patients (breast cancer: 76.0%; ovarian cancer: 13.6%) were randomized to placebo (n=75) or d-MPH (n=77); 132 patients completed. Significant improvement in the FACIT-F Total Score (Weeks 1, 5, 6, 7, 8; p<0.05) and HSCS Memory Subscale (Week 8; p<0.05) was observed in the d-MPH group versus placebo. Mean highest d-MPH dose was 27.7 mg/day. Common adverse events (AEs), headache (d-MPH: 40.8%; placebo: 33.3%) and nausea (d-MPH: 27.6%; placebo: 7.7%), were mostly mild to moderate. Serious AEs were reported in 2 subjects (placebo only). Conclusions: Dexmethylphenidate was well-tolerated and significantly more effective than placebo in improvement of fatigue and impaired memory after chemotherapy in adult cancer patients. For patients with fatigue and memory impairment after chemotherapy, dexmethylphenidate therapy should strongly be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene Celgene Celgene Celgene
Hypercalcemia Due to Endogenous Overproduction of Active Vitamin D in Identical Twins With Cat-Scratch Disease
Authors: X Bosch
Journal: JAMA (1998)

Context.—The extrarenal synthesis of active vitamin D sterols has a central causative role in the hypercalcemia associated with various granulomatous diseases.Objective.—To study the calcium metabolism in patients with cat-scratch disease who have hypercalcemia.Design.—Case report.Setting.—University hospital in Barcelona, Spain.Patients.—Two identical twins who developed asymptomatic hypercalcemia during the acute phase of cat-scratch disease.Main Outcome Measures.—Serial measures of calcium homeostasis and metabolism over a 2-month period.Results.—On admission and 6 and 7 days later, both patients were found to have increased levels of serum and urinary calcium, serum phosphate, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D], whereas they had normal values of serum 25-hydroxyvitamin D and urinary cyclic adenosine monophosphate and decreased serum concentrations of intact parathyroid hormone. Sixteen and 20 days after admission, these abnormalities had resolved without treatment. A direct correlation was observed between the serum 1,25(OH)2D levels and both the serum and 24-hour urinary calcium concentrations. Also, the concentrations of calcium and 1,25(OH)2D paralleled the clinical activity of the infectious disease over the period these parameters were measured.Conclusions.—Our cases provide evidence that cat-scratch disease can produce hypercalcemia through the unregulated production of the metabolite 1,25(OH)2D. Cat-scratch disease should be added to the list of granuloma-forming diseases that are responsible for 1,25(OH)2D-mediated hypercalcemia.
Salmonella enterica serotype Paratyphi A carrying CTX-M-15 type extended-spectrum beta-lactamase isolated from a Japanese traveller returning from India, Japan, July 2013
Authors: M Mawatari, Y Kato, K Hayakawa, M Morita, K Yamada, K Mezaki, T Kobayashi, Y Fujiya, S Kutsuna, N Takeshita, S Kanagawa, M Ohnishi, H Izumiya, N Ohmagari
Journal: Eurosurveillance (2013)

Emerging drug resistance in Salmonella Typhi and S. Paratyphi is a substantial public health concern. We report what appears to be the first case and isolation of multidrug resistant S. Paratyphi A carrying CTX-M-15-type extended-spectrum beta-lactamase from a Japanese traveller returning from India.
Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.
Authors: S J Spencer, J Rabinovici, S Mesiano, P C Goldsmith, R B Jaffe
Journal: Journal of Clinical Investigation (1992)

Recent experimental data have revealed that activins and inhibins exert pivotal effects on development. As part of our studies on growth and differentiation of the human fetal adrenal gland, we examined the subunit localization, as well as the mitogenic and steroidogenic actions of activin and inhibin in human fetal and adult adrenals. All three activin and inhibin subunit proteins (alpha, beta A, and beta B) were detected in the fetal and adult adrenal cortex. Immunoreactive activin-A dimer was demonstrated in midgestation fetal and neonatal adrenals. ACTH1-24-stimulated fetal adrenal cell expression of alpha and beta A subunit messenger RNA. In addition, ACTH elicited a rise in levels of immunoreactive alpha subunit secreted by fetal and adult adrenal cells. Human recombinant activin-A inhibited mitogenesis and enhanced ACTH-stimulated cortisol secretion by cultured fetal zone cells, but not definitive zone or adult adrenal cells. Recombinant inhibin-A had no apparent mitogenic or steroidogenic effects. Thus, activin selectively suppressed fetal zone proliferation and enhanced the ACTH-induced shift in the cortisol/dehydroepiandrosterone sulfate ratio of fetal zone steroid production. These data indicate that activin-A may be an autocrine or paracrine factor regulated by ACTH, involved in modulating growth and differentiated function of the human fetal adrenal gland.