tbuckley/cabot-search huggingface dataset:
Teenagers' use of Emergency Contraception in a General Practice
Authors: C J Seamark, D J Pereira Gray
Journal: Journal of the Royal Society of Medicine (1997)

British teenagers who become pregnant commonly express ignorance about emergency contraception. A case-note survey was conducted in a general practice serving about 14 200 people in a Devon market town. Of the 373 registered girls aged 15–19 years, 59 (16%) had consulted for emergency contraception, 19 of them more than once. The oral method (Yuzpe regimen) was prescribed eighty times and 2 girls became pregnant. 4 of the 59 girls who used emergency contraception had subsequent unwanted pregnancies. A consultation for emergency contraception presents an opportunity to discuss more reliable and acceptable methods of contraception.
Decreased expression of HLA-DQ and -DR on blood monocytes, sputum macrophages and monocyte-derived macrophages in patients with cystic fibrosis
Authors: Thomas P. Hofer, Marion Frankenberger, Irene Heimbeck, Dorothe Burggraf, Matthias Wjst, Adam K.A. Wright, Maria Kerscher, Susanne Nährig, Rudolf M. Huber, Rainald Fischer, Löms Ziegler-Heitbrock
Journal: European Respiratory Journal (2014)

We studied HLA class II molecules in adult patients with cystic fibrosis (CF) and healthy subjects at the protein level (flow cytometry) and mRNA level (RT-PCR) in blood monocyte subsets, sputum macrophages and monocyte-derived macrophages as putative contributors to the CF phenotype.  In healthy donors we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity (ΔMnI) on classical blood monocytes, with the lowest value of 2 ΔMnI. In F508del homozygous CF patients the average ΔMnI was low (1.80). 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ group1 ) and 36 below (average 1.24 ΔMnI, CF-DQ group2 ). In healthy controls the CD16-positive monocyte subset expressed higher levels of HLA-DQ (10.88 ΔMnI) when compared to the classical monocytes but again the CF-DQ group2  patients showed much lower levels for HLA-DQ on these cells (2.48 ΔMnI). DQ expression levels on sputum macrophages and monocyte-derived macrophages (MDM) exhibit dramatically decreased levels in the CF-DQ group2  cases.  At mRNA level we found a seven-fold decrease for DQβ1 transcripts in monocytes from the CF-DQ group2  patients. CRP levels of the patients are correlated with low HLA-DQ (p=0.024) and -DR (p=0.0007) protein expression.  In vitro  HLA-DQ and -DR expression on blood monocytes was also decreased after LPS-treatment (p  The data demonstrate that CF patients showed reduced expression of MHC class II molecules in monocytes and macrophages, which is most pronounced for HLA-DQ both at the mRNA and protein level an.
Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study.
Authors: R P Abratt, W R Bezwoda, G Falkson, L Goedhals, D Hacking, T A Rugg
Journal: Journal of Clinical Oncology (1994)

PURPOSE The aim of this study was to evaluate the efficacy and toxicity of gemcitabine at higher doses than had been used previously in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Eighty-four patients (65 men, 19 women; age range, 35 to 75 years; mean age, 59 years) with locally advanced or metastatic pathologically documented NSCLC were enrolled. Patients had bidimensionally measurable disease, as defined by computed tomographic (CT) scan or chest x-ray. A total of 28.6% had previously been surgically treated, while 9.5% had received radiotherapy. Fifty-three patients commenced at a dose of 1,000 mg/m2, and 31 at a dose of 1,250 mg/m2. Patients were to receive two dose escalations of 25%, provided that overall toxicity was no worse than World Health Organization (WHO) grade 1 or WHO grade 0 for platelets. Responding patients were reviewed and validated by a blinded oncology review board (ORB) of experts not involved with the study. Of the original 84 patients enrolled, 76 were assessable. RESULTS The overall response rate was 20% (95% confidence interval [CI], 11.6% to 30.8%). There were two complete responses (3%) and 13 partial responses (17%). Hematologic toxicity was negligible. WHO grade 3 WBC toxicity occurred in 0.9% of doses and WHO grade 4 in 0.1%. WHO grade 3 and 4 thrombocytopenia occurred in 0.1% and 0.1% of all doses, respectively. Nonhematologic toxicity was minor and easily controlled. Common side effects included peripheral edema, asthenia, and transient malaise. CONCLUSION The single-agent efficacy of gemcitabine is equivalent to other agents commonly used to treat NSCLC. Gemcitabine has an unusually mild side effect profile for such an active agent. The nausea and vomiting experienced with gemcitabine are mild and generally well controlled with standard antiemetics; 5-HT3 receptor antagonists are typically not required. The use of gemcitabine does not cause significant alopecia, and hematologic toxicity is modest and unlikely to require hospitalization. Gemcitabine may have a role as monotherapy in patients with inoperable NSCLC.
Treatment of stage IV favorable histology Wilms tumor with incomplete lung metastasis response after chemotherapy: A report from Children’s Oncology Group study AREN0533.
Authors: David B. Dix, Eric J. Gratias, Nita Seibel, James Robert Anderson, Elizabeth Anne Mullen, James I. Geller, Geetika Khanna, John A. Kalapurakal, Elizabeth Jones Perlman, Peter F. Ehrlich, Marcio H. Malogolowkin, Paul Edward Grundy, Jeffrey Dome
Journal: Journal of Clinical Oncology (2014)

10001 Background: National Wilms Tumor Study-5 showed that patients with stage IV Favorable Histology Wilms Tumor (FHWT) had 4-year event-free survival (EFS) and overall survival (OS) estimates of 75% and 86% when treated with Regimen DD4A (vincristine/dactinomycin/doxorubicin) and whole lung irradiation (XRT). To decrease relapse rates while subjecting fewer patients to XRT, the AREN0533 study evaluated whether therapy can be tailored based on the completeness of lung metastasis response after 6 weeks of DD4A chemotherapy. Patients showing complete resolution of lung metastases at week 6 continued DD4A without lung XRT. Patients with incomplete lung metastasis response ("slow incomplete response"=SIR) continued DD4A with the addition of cyclophosphamide/etoposide (Regimen M) and lung XRT. Interim analysis for the SIR group is the subject of this report. Methods: Patients were enrolled between February 2007 and February 2013 after undergoing risk assignment on the AREN03B2 Renal Tumor Biology and Classification study. The completeness of lung metastasis response was determined by central radiology review after 6 weeks of chemotherapy. The null hypothesis was that 4-year EFS for SIR when treated with DD4A therapy is 75%. The study was designed to detect a decrease in the risk of failure corresponding to 4-year EFS of 84%. Results: Among 391 patients enrolled, 279 had isolated lung metastases, of which 163 (58%) had SIR. At interim analysis in June 2013, the number of expected events under the null hypothesis was 38.6, yet only 15 events were observed. This difference was sufficient to reject the null hypothesis and conclude that Regimen M is superior to the historical standard (p=0.0001, Woolson 1-sample log rank test). The 3-year EFS and OS estimates for SIR patients were 88% (95% CI: 81%, 93%) and 92% (95% CI: 86%, 96%). Grade 3 or higher hematological toxicity was the most common toxicity observed with Regimen M, affecting 60% of patients. There were no unexpected toxicities. Conclusions: Patients with stage IV FHWT with SIR of lung metastases showed superior EFS with the addition of cyclophosphamide/etoposide compared to the historical standard. Clinical trial information: NCT00379340.
Immunostimulatory CpG Oligodeoxynucleotides Enhance the Immune Response to Vaccine Strategies Involving Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Hsin-Ming Liu, Sally E. Newbrough, Sudershan K. Bhatia, Christopher E. Dahle, Arthur M. Krieg, George J. Weiner
Journal: Blood (1998)
Non-invasive detection of diaphragmatic weakness in acid maltase deficiency (AMD)
Authors: Antonella LoMauro, Gauthier Remiche, Maria Grazia D'Angelo, Andrea Aliverti
Journal: European Respiratory Journal (2012)

Patients with AMD, a glycogen storage disease resulting in loss of skeletal muscle function, become ventilator dependent when respiratory muscles, particularly the diaphragm, are significantly involved. To identify predictive factors of diaphragmatic weakness in AMD, we studied 10 untreated AMD patients and 8 healthy controls. Supine postural drop of vital capacity (ΔVC) was measured by spirometry, while rib cage (RC) and abdominal (AB) volume variations by opto-electronic plethysmography during quite breathing and slow vital capacity in seated and supine posture. RC and AB contributions to tidal volume (VT), inspiratory capacity (IC) and expiratory reserve volume (ERV) were derived. Diaphragmatic weakness, defined as ΔVC>25% (Fromageot et al,2001), was present in 3 patients (DW). Posture had a significant effect on IC and AB volume changes during IC and ERV (left and central panel) in controls and patients without DW (noDW). Conversely, in DW patients IC and AB volume changes during IC did not vary with posture, while AB contribute paradoxically (negative values) to ERV in supine position. DW patients also showed negative (i.e., paradoxical inward movement) AB contribution to VT which correlated with ΔVC (right panel). AB volume variations in both DW and noDW patients were generally lower than controls. In conclusion, abdominal displacement during VT and VC maneuver is a good indicator of diaphragmatic weakness in AMD.

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Abstract 12407: Three Dimensional and Doppler Echocardiographic Parameters Predict Response to Cardiac Resynchronization Therapy
Authors: Carolin Sonne, Lorenz Bott-Fluegel, Hasema Lesevic, Simon Hauck, Martin Hadamitzky, Petra Wolf, Jorg Hausleiter, Albert Schomig
Journal: Circulation (2012)

Background: The evaluation of predictive parameters for response to cardiac resynchronization therapy (CRT) is the focus of several studies. Nevertheless, the exact reasons for lack of response are...
High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency.
Authors: G A Smith, L E Damon, H S Rugo, C A Ries, C A Linker
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the impact of high-dose cytarabine (ARA-C) (HDAC) dose modification, based on renal function, on the incidence of neurotoxicity (NT). PATIENTS AND METHODS We retrospectively analyzed the records of 256 patients treated with HDAC (&gt; or = 2.0 g/m2 per dose) for acute myelogenous leukemia (AML) at the University of California, San Francisco (UCSF). From 1985 to 1994, a total of 358 cycles of HDAC were administered, using either a twice-daily schedule (n = 208) or a once-daily regimen (n = 48). In 1989, a dose-modification algorithm was initiated at our institution, which reduced ARA-C doses in the setting of renal insufficiency (RI). For patients with a serum creatinine (Cr) level of 1.5 to 1.9 mg/dL during treatment, or an increase in Cr during treatment (deltaCr) of 0.5 to 1.2 mg/dL, ARA-C was decreased to 1 g/m2 per dose. For patients with a Cr &gt; or = 2.0 mg/dL or a deltaCr greater 1.2 mg/dL, the dose was reduced to 0.1 g/m2/d. RESULTS Overall, the incidence of NT was 16% (34 of 208) for patients treated with twice-daily HDAC and 0% (none of 48) for patients treated with daily HDAC (P = .003). NT occurred more often in patients treated on a twice-daily schedule with 3 g/m2 per dose compared with 2 g/m2 per dose (25% v 8%; P = .009). NT occurred in 55% of the twice-daily-treated patients with RI, compared with 7% of those with normal renal function (P = .00001). In patients with RI, NT occurred in none of 11 dose-modified cycles versus five of 11 (45%) total unmodified cycles (P = .01). None of 14 patients treated with once-daily HDAC given during RI developed NT, compared to 55% of patients (23 of 42) receiving twice-daily HDAC during RI (P = .009). By univariate analysis, NT was not associated with patient age or serum alkaline phosphatase, but NT was significantly increased in patients treated with twice-daily HDAC when the serum bilirubin was &gt; or = 2.0 mg/dL compared with twice-daily HDAC given when the total bilirubin was less than 2.0 mg/dL (33% v 14%; P = .017). Multivariate analysis confirmed that RI was the most significant risk factor associated with the development of NT. CONCLUSION HDAC NT is strongly associated with RI. The risk of HDAC NT can be reduced by the following: (1) routinely reducing the ARA-C dose from 3 to 2 g/m2 per dose; (2) modifying the ARA-C dose based on daily Cr values; and (3) administering HDAC on a once-daily rather than twice-daily schedule.
Scoring of hand eczema: good agreement between patients and dermatological staff
Authors: A. Carlsson, A. Gånemo, C.D. Anderson, B. Meding, B. Stenberg, Å. Svensson
Journal: British Journal of Dermatology (2011)

Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand.To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema.In a study of 62 patients (36 women and 26 men, age range 19-75 years), the patient's own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patient's visit to the clinic. Individual area scores were summed to a total score.The overall agreement was good, with an interclass correlation (ICC) of 0·61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0·78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand.Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.
Abstract P28: Clotting Function is Impaired Within Minutes of Return of Spontaneous Circulation in a Swine Model of Cardiac Arrest
Authors: Nathan White, Benjamin Leong, Erika Martin, Donald Brophy, Mary Peberdy, Joseph Ornato, Nathan Menke, Kevin Ward
Journal: Circulation (2009)

Introduction: Coagulopathy predicts mortality during the post-cardiac arrest syndrome and coagulation’s role during the post-arrest period has been identified as a critical knowledge gap by the Int...
Cultivation of Human Breast Carcinomas&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Etienne Y. Lasfargues, Luciano Ozzello
Journal: JNCI Journal of the National Cancer Institute (1958)

A method was developed for the cultivation of human breast carcinoma cells. This technique, taking advantage of the weak intercellular bonds within the tumor, harvests the cells "spilling" out of the tumor stroma when thin slices are cut with a razor blade. This suspension was sensitive to customary enzymatic concentrations which therefore cannot be used in the preliminary step of preparation. Agitation, even the slow motion of the roller drum, was unfavorable to the growth of the neoplastic cells which have to be explanted in resting tubes. Continuous cultivation of human breast carcinoma cells was achieved for the first time. The cultures, derived from a mammary duct-cell carcinoma of no special type, are now in their 6th month of life in vitro and extremely proliferative. A regular growth rate of the neoplastic cells appeared to be dependent on the presence in the medium of mucopolysaccharides introduced in the form of umbilical-cord extract. Human placental serum and beef amniotic fluid, whose high content in estrogenic hormones is well known, also had a beneficial effect. Folic acid in a 2.5 mM concentration appeared favorable to the growth of the cancer cells. However, a possible antagonism with cord extract was considered in relation to the spindle-shaped transformation which occurred in the epithelial cells when transferred from a folic acid medium to one enriched with cord extract.
Comprehensive characterization of the lung proteasome
Authors: Anne Caniard, Juliane Merl, Stephanie Hauck, Oliver Eickelberg, Silke Meiners
Journal: European Respiratory Journal (2014)

Protein homeostasis is mainly regulated by the proteasome playing an essential role in cellular signaling and immune response. The 20S core particle of the proteasome encloses two sets of three active sites. Upon inflammation, expression of immuno-catalytic subunits is induced. Combinations of standard and immuno-subunits result in formation of constitutive, mixed and immuno-proteasomes. To become fully activated, the 20S core associates with regulatory particles. Whereas catalytic subunits control cleavage specificity, regulators modulate substrate specificity and turnover. Of note, proteasome composition is organ-, cell-, and cell compartment-specific. While changes in proteasome composition are known to be involved in diseases in several organs, they were never studied in the lung.  Here, we provide a comprehensive description of the different proteasome complexes in the lung. For that, we isolated proteasome complexes from whole lung homogenates and from A549 cells. A first round of mass spectrometry analyses allowed us to identify all proteasome subunits and regulators, as well as new proteasome interacting proteins. In addition, we characterized several unreported prost-translational modifications (PTM). Currently, we are validating our newly identified proteasome interactors and the role of PTMs for proteasome function. In particular, we are focusing on a new deuibiquitinase, known to be down-regulated in lung cancer; a thioredoxin-like domain protein; and ribosomal subunits.  This study will help us to understand the possible involvement of proteasome function in the development of lung diseases, and contributes to the identification of novel therapeutic targets that regulate protein homeostasis.
Naturally Occurring Tumors and Other Lesions of the Digestive Tract in Untreated C57BL Mice
Authors: C. Rowlatt, L. M. Franks, M. U. Sheriff, F. C. Chesterman
Journal: JNCI Journal of the National Cancer Institute (1969)

A wide range of tumors of the intestinal tract was found in 97 old C57BL mice in a series of 962 mice in which a full necropsy was carried out. The epithelial tumors included polyps in the forestomach (2), glandular stomach (1), duodenum (41), ileum (2), cecum (5), and colon (2). Carcinomas were in the forestomach (1), duodenum (4), jejunum (7), ileum (8), and cecum (2). There were 2 disseminated carcinomas. Nineteen hypertrophic duodenal plaques were also found. In addition, there were 4 neurofibromas, 1 hemangioma, and 9 reticuloendothelial tumors localized to the intestinal tract.
Dose intensity analysis of chemotherapy regimens in ovarian carcinoma.
Authors: L Levin, W M Hryniuk
Journal: Journal of Clinical Oncology (1987)

The relationship between outcome and dose intensity was analyzed for first-line chemotherapy of advanced ovarian cancer using a particular CHAP (cyclophosphamide, hexamethylmelamine, Adriamycin [Adria Laboratories, Columbus, OH], cisplatin) regimen as the standard. Previously described techniques were used to calculate the average dose intensity of regimens containing one, two, three, or all four drugs of CHAP, relative to the standard. The average relative dose intensity, especially the relative dose intensity of cisplatin, correlated significantly with clinical response and with median survival time (MST) of the entire group (not just the remitters). There was a distinct advantage for multiagent regimens over single alkylating agents and especially for multiagent regimens containing cisplatin. Survival correlated with response rate (of multiagent regimens). This analysis suggests that dose intensity is a determinant of treatment outcome. Prospective randomized trials would be required to test whether, and to what extent, dose intensity determines outcome independently of total amount of drug given, performance status, or other factors. If dose intensity does determine outcome, methods of increasing it should be tested in an attempt to improve treatment results.
Phase I and Pharmacokinetic Trial of Gemcitabine in Patients With Hepatic or Renal Dysfunction: Cancer and Leukemia Group B 9565
Authors: Alan P. Venook, Merrill J. Egorin, Gary L. Rosner, Donna Hollis, Sridhar Mani, Michael Hawkins, John Byrd, Raymond Hohl, Daniel Budman, Neal J. Meropol, Mark J. Ratain
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To ascertain if hepatic or renal dysfunction leads to increased toxicity at a given dose of gemcitabine and to characterize the pharmacokinetics of gemcitabine and its major metabolite in patients with such dysfunction. PATIENTS AND METHODS: Adults with tumors appropriate for gemcitabine therapy and who had abnormal liver or renal function tests were eligible. Patients were assigned to one of three treatment cohorts: I—AST level less than or equal to two times normal and bilirubin level less than 1.6 mg/dL; II—bilirubin level 1.6 to 7.0 mg/dL; and III—creatinine level 1.6 to 5.0 mg/dL with normal liver function. Doses were explored in at least three patients within each cohort. Gemcitabine and its metabolite were to be measured in the blood in all patients. RESULTS: Forty patients were assessable for toxicity. Transient transaminase elevations were observed in many patients but were not dose limiting. Patients with AST elevations tolerated gemcitabine without increased toxicity, but patients with elevated bilirubin levels had significant deterioration in liver function after gemcitabine therapy. Patients with elevated creatinine levels had significant toxicity even at reduced doses of gemcitabine, including two instances of severe skin toxicity. There were no apparent pharmacokinetic differences among the three groups or compared with historical controls. CONCLUSION: If gemcitabine is used for patients with elevations in AST level, no dose reduction is necessary. Patients with elevated bilirubin levels have an increased risk of hepatic toxicity, and a dose reduction is recommended. Patients with elevated creatinine levels seem to have increased sensitivity to gemcitabine, but the data are not adequate to support a specific dosing recommendation.