tbuckley/cabot-search huggingface dataset:
Ultrastructural Survey of Primary Liver Cell Carcinomas From Uganda&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: G. T. O'Conor, T. S. Tralka, E. Henson, C. L. Vogel
Journal: JNCI Journal of the National Cancer Institute (1972)

Seventeen surgical biopsy specimens from Ugandan patients with liver cell carcinoma were studied by electron microscopy. The ultra-structural features observed in this series are similar to those previously reported by others. A narrow range in the degree of differentiation of tumor cells is noted, but in most cases they are easily recognizable as of hepatic origin. No morphologic correlation with a-feto-protein in the serum or with Australia antigen was found and no virus particles were seen in the material examined. Despite the absence of significant new findings in this survey, it is suggested that electron microscopic studies in liver cancer should be pursued, but more specifically directed toward the investigation of in vitro cultures and the search for virus therein. Application of special techniques for localization of fetal protein production might also provide new information on the relationship of this antigen to other functions of the hepatic cell during tumorigenesis and following therapy.
Etiology and epidemiology of prescriptive errors in the practice of clinical oncology
Authors: E. Gil Deza, A. Negro, M. S. Muiño, D. Juarez, S. Aguirre, F. Negro, E. Morgenfeld, E. J. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2008)

6591 Background: Last year we studied the “Standard therapy deviations in the practice of clinical oncology” (ASCO 2007- Abstract # 6504). In this study, a larger population of patients (pt) (n=8845) was analyzed. We focused on type II prescription errors (pe) which doubled the previous study. Methods: Between October 2004 and November 2007, 78.700 prescriptions for 8,485 pt were progressively entered into a database and compared with the national and international therapeutic guidelines recommendations (Evidence Based Oncology). The pe were identified and the following parameters were registered: attending physician, pt diagnosis, error subtype, pt risk, probable cause of the error and date. Pt's risk (it was defined as the potential harm to be performed to the pt from the consigned error). Three risk levels were recognized (low, moderate and high) according to potential toxicity (grade III-IV) attributable to the pe. All the data was tabulated and analyzed. Results: Three hundred and ninety seven pe were identified. The most frequent diagnoses involved were: Breast (29%), Non Hodgkin Lymphoma (12%) and Prostate (12%). The most frequent error subtype was related to drug dosage (28%), followed by duration of the therapy (tx) (18%), confusion with the drugs or schedules (15%), tx not according to the tumor stage (15%) or diagnosis (10%). The pt's risk was: high in 167 Pt (42%), moderate in 32 Pt (8%) and low in 198 Pt (50%). The reasons for the pe. are to be presented. Conclusions: 1) The pe rate was 5 out of 1,000 oncological prescriptions.2) Although the most frequent single error is related to the drug dosage (28%), inadequate tx selection (schedule, stage and diagnosis) represented 40% of the detected pe. 3) Fifty percent of the pe represent a moderate or high risk to the pt health 4) The probable causes of the errors are due to inadequate compliance of standards related to medical records and clinical guidelines. No significant financial relationships to disclose.
FRI0278 Life-Threatening Onset of Systemic Vasculitis Requiring Intensive Care Unit Admission: A Case Series
Authors: S. Monti, L. Cavagna, S. Pieropan, C. Montecucco, R. Caporali
Journal: Annals of the Rheumatic Diseases (2015)

Onset of ANCA-associated vasculitis (AAV) can be abrupt with life-threatening manifestations requiring Intensive Care Unit (ICU) admission. A high level of suspicion leading to prompt diagnosis is essential. Our objective was to investigate the epidemiologic characteristics and the type of life-threatening manifestations.Medical records of AAV patients were analysed, selecting those with an ICU onset to identify predictive signs or symptoms and past medical history warnings useful for diagnosis.Out of 90 patients with AAV, 10 (11.1%) showed an ICU onset. The most frequent AAV diagnosed in the ICU was eosinophilic granulomatosis with polyangiitis (EGPA) (60%), followed by granulomatosis with polyangiitis (GPA) (20%) and microscopic polyangiitis (MPA) (20%). Cardio-pulmonary involvement was the main cause for ICU admission (70%) and significantly distinguished the ICU onset group from other AAV. The most frequent anamnestic warnings were history of asthma (50%), nasal polyps (30%), eosinophilia (30%). Symptoms shortly preceding ICU admission were arthralgia, fever (30%) and purpuric lesions (20%). ANCA were positive in 60% of patients. Mean Birmingham Vasculitis Activity Score (BVAS) at diagnosis was 16±8.43 and 0.88±1.45 at the end of follow up. All patients survived with a 10% rate of chronic kidney disease and a mean Vasculitis Damage Index (VDI) of 2±1.15.Keeping a high level of suspicion for AAV is mandatory, particularly when treating life-threatening onset manifestations in the ICU. A history of asthma, nasal polyps, eosinophilia and arthralgia should always be investigated. ANCA are negative in about half of cases, therefore clinical expertise and strict collaboration with the rheumatologist are still pivotal.
Abstract 14063: Safety and Outcomes of the 56 Holes New Open Irrigated Sf Catheter During Catheter Ablation of Atrial Fibrillation
Authors: Luigi Di Biase, Pasquale Santangeli, Francesco Santoro, J. David Burkhardt, Sanghamitra Mohanty, Prasant Mohanty, Javier Sanchez, Rodney Horton, Chintan Trivedi, Rong Bai, Dhanunjay Lakkireddy, Madhu Reddy, Salwa Beheiry, Richard Hongo, Viles Gonzalez Juan F, Steven Hao, Claude S Elayi, Jason Zagrodzky, Andrea Natale
Journal: Circulation (2013)

Introduction: Success rate of radiofrequency (RF) catheter ablation of atrial fibrillation (AF) has improved with the use of open irrigated catheter. Recently a new open irrigated catheter with 56 ...
Genotypic bases of EGFR inhibitors pharmacological actions
Authors: S. Perea, D. Oppenheimer, M. Amador, G. Cusati, S. Baker, C. Takimoto, A. Maitra, C. Iacobuzio-Donahue, M. Hidalgo
Journal: Journal of Clinical Oncology (2004)

3005 Background: Factors that predict the activity of EGFR inhibitors are not known. The EGFR gene has a highly polymorphic region in an intron 1 that consist of a variable number of CA repeats that regulates gene transcription. This study tested the hypothesis that polymorphic variations of this region influence the response to these drugs. Methods: The number of CA repeats was determined by PCR-based methods in a panel of 13 cell lines lacking EGFR gene amplification, pair normal and tumor DNA from 30 subjects with cancer, and skin biopsies from 19 patients treated with gefitinib. Phenotypic modifications were achieved by siRNA technology. QRT-PCR was used to measure EGFR mRNA levels. The response to the drugs in cell lines was measured by MTT assays. The response to the drug in patients was assessed by grading skin toxicity and p27 expression using quantitative immunohistochemistry in skin biopsies. Results: Cell lines with short CA segments (sum of alleles <36) were significantly more susceptible to 1 uM erlotinib in vitro with a relative growth of 20 % when compared to cell lines with longer segments (sum of alleles >35), and a relative growth of 80% (p=0.04). Cells with short CA segments have higher EGFR mRNA and protein expression. Silencing of EGFR mRNA expression in a cell with 16/16 genotype using siRNA to reduce the mRNA levels to that of a 20/20 genotype induced drug resistance; and thus demonstrated the concept in vitro. The number of CA repeats was identical in normal and tumor DNA from 30 subjects indicating is a conserved region in tumor and normal tissues from each subject. Patients with short CA segments had a higher frequency of rash (61 %) versus those with long CA repeats (17 %) when treated with gefitinib (p = 0.06). In addition, the nuclear expression of p27 in post-treatment skin biopsies was higher in subjects with short vs long CA repeats (7721 vs. 2910 ACIS composite score). Conclusions: These data indicates that individuals and tumors with short CA repeat segments in the regulatory intron 1 of the EGFR are more susceptible to the pharmacological effects of EGFR inhibitors; and therefore provides an explanation that the occurrence of a rash may be linked to therapeutic effects of these drugs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Genentech; OSIP AstraZeneca; Genentech; OSIP AstraZeneca; Genentech; OSIP
급성 신기능상실이 합병된 급성 A형간염의 임상상
Authors: 송기섭 ( Kee Sup Song ), 김민주 ( Min Ju Kim ), 장창수 ( Chang Soo Jang ), 정혁상 ( Hyuk Sang Jung ), 이현희 ( Hyun Hee Lee ), 권오상 ( Oh Sang Kwon ), 김연수 ( Yun Soo Kim ), 최덕주 ( Duck Joo Choi ), 김주현 ( Ju Hyun Kim ), 하승연 ( Seung Yeon Ha )
Journal: Clinical and Molecular Hepatology (2007)
Phase Ib study of recombinant human Apo2L/TRAIL plus irinotecan and cetuximab or FOLFIRI in metastatic colorectal cancer (mCRC) patients (pts): Preliminary results
Authors: L. Yee, H. A. Burris, M. Kozloff, Z. Wainberg, M. Pao, S. Skettino, W. Novotny, B. Durbin, J. Weston, H. Hurwitz
Journal: Journal of Clinical Oncology (2009)

4129 Background: Preclinical data suggest that recombinant human Apo2 ligand/TNF-related apoptosis-inducing ligand (rhApo2L/TRAIL) induces tumor cell death through pro-apoptotic receptors DR4 and DR5. In specific mouse xenograft colon cancer models, tumors regressed in the majority of mice given rhApo2L/TRAIL and irinotecan. In this ongoing study of rhApo2L/TRAIL in previously treated mCRC pts, the primary objectives are to assess the safety and pharmacokinetics of rhApo2L/TRAIL combined with irinotecan and cetuximab or FOLFIRI. Methods: As of 12/12/08, 30 pts have received rhApo2L/TRAIL (on Days 1–5) with irinotecan (on Day 1) and cetuximab (on Days 1, 8, and 15) in 21-day cycles; rhApo2L/TRAIL dose cohorts range from 1.5–8 mg/kg/day. 5 pts have received rhApo2L/TRAIL 9 mg/kg (on Days 1–3) with FOLFIRI (leucovorin, 5-FU, and irinotecan on Day 1) in 14-day cycles. Results: In the first cohort, rhApo2L/TRAIL was given at 4 mg/kg/d with irinotecan (350 mg/m 2 ) and cetuximab; the first 3 pts developed Grade 3–4 neutropenia. The study was amended to allow irinotecan dose reductions to 300 mg/m 2 for pts at risk for irinotecan-related toxicities and patients were started on a lower dose of Apo2L/TRAIL at 1.5 mg/kg/d. An additional 32 pts received rhApo2L/TRAIL at 1.5–9 mg/kg/d. The most common adverse events thus far are diarrhea, fatigue, and nausea. A pt with anemia at screening developed Grade 4 anemia DLT. 2 pts (1 with progressive liver disease) discontinued therapy due to elevated ALT. Conclusions: Preliminary data indicate that rhApo2L/TRAIL can be safely combined with irinotecan-based regimens. Full data will be available by June 2008. A phase II study of rhApo2L/TRAIL with FOLFIRI should provide more information on safety, efficacy, and a potential diagnostic for rhApo2L/TRAIL. [Table: see text]
Effects of GLP-1 Receptor Agonists on Heart Rate and the Autonomic Nervous System Using Holter Electrocardiography and Power Spectrum Analysis of Heart Rate Variability
Authors: Yuki Nakatani, Atsuhiko Kawabe, Mihoko Matsumura, Yoshimasa Aso, Takanori Yasu, Nobuyuki Banba, Takaaki Nakamoto
Journal: Diabetes Care (2015)

Long- and short-acting glucagon-like peptide 1 receptor agonists (GLP-1RAs) liraglutide and lixisenatide, which are available for diabetes therapy, may act on the autonomic nervous system to increase heart rate (1,2). We performed a prospective, single-center, randomized, open-label study with a 1:1 allocation ratio using a 24-h Holter electrocardiogram to compare the effects of these GLP-1RAs on the autonomic nervous system. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients participating in this study. The study is registered at University Hospital Medical Information Network Clinical Trials Registry (UMI17770).

Sixty patients with type 2 diabetes who were admitted for diabetes treatment and had not received dipeptidyl peptidase-4 inhibitors or GLP-1RAs were randomly divided into a liraglutide (age 64.9 ± 12.7 years, HbA1c 10.3 ± 2.5% [89.1 mmol/mol], BMI 24.6 ± 4.8 kg/m2, diabetes duration 7.8 ± 7.8 years) or …
How an acute rise in arterial pressure damages arterioles: Electron microscopic changes during angiotensin infusion
Authors: F. S. GOLDBY, L. J. BEILIN
Journal: Cardiovascular Research (1972)

Angiotensin infusion was used to cause a sustained rise in arterial pressure in rats. After 1 hr of raised pressure electron microscopy of segments of gut arterioles showed focal breaks in the endothelium and amorphous deposits in the media displacing and disrupting smooth muscle cells. Intravenously injected carbon particles were found in the amorphous deposits, sometimes in relation to electron-dense material resembling fibrin. The damage was patchy and confined to dilated segments of arterioles. These appearances were consistent with the passage of plasma into the media through the damaged endothelium as a consequence of the raised arterial pressure.
p53 protein accumulation predicts poor response to tamoxifen therapy of patients with recurrent breast cancer.
Authors: E M Berns, J G Klijn, W L van Putten, H H de Witte, M P Look, M E Meijer-van Gelder, K Willman, H Portengen, T J Benraad, J A Foekens
Journal: Journal of Clinical Oncology (1998)

PURPOSE Mutations of the p53 gene are frequently observed in primary breast cancer and accumulation of p53 protein has been used as a surrogate marker of p53 inactivation. Previous studies have shown that p53 accumulation is related to poor prognosis in primary breast cancer. We studied whether p53 protein accumulation is a predictive factor for response to tamoxifen treatment in patients with recurrent breast cancer. PATIENTS AND METHODS Levels of p53, estrogen receptor (ER), progesterone receptor (PgR), and urokinase-type plasminogen activator (uPA) were assayed in cytosolic extracts derived from primary tumors of 401 tamoxifen-naive patients who developed recurrent disease. All patients in the study received tamoxifen therapy upon relapse (median follow-up, 69 months). Association of tested factors with response to tamoxifen treatment was studied by logistic regression analysis, and with survival after the start of treatment by Cox univariate and multivariate regression analysis. RESULTS p53 levels (median, 0.23 ng/mg protein) were not related to ER or PgR levels, but positively correlated with uPA (P &lt; .0001). In a test for trend, we observed an association of p53 protein levels with response to tamoxifen therapy. When dichotomized (at the median value), 42% in the p53-high versus 56% in the p53-low group showed a response. In multivariate analysis, including patient and tumor characteristics, p53 accumulation retained significance with the rate of response (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.31 to 0.74; P &lt; .001). Also in multivariate analysis, reduced survival after the start of tamoxifen therapy was observed in the p53-high group (relative hazards rate [RHR], 1.56, 95% CI, 1.17 to 2.10; P = .002). A statistically significant association between p53 levels and decreased tamoxifen response was seen only in the subset of patients whose tumors expressed low levels of ER or PgR (&lt;75 fmol/mg protein). CONCLUSION Measurement of primary tumor p53 levels may be effective in predicting response to tamoxifen therapy in recurrent breast disease. However, more confirming studies on the association between p53 protein accumulation and response to antiestrogen therapy are needed before tumor p53 levels can be used in routine clinical practice.
Abstract P346: Novel Protein Glycan Derived Marker of Systemic Inflammation is Associated with Incident Coronary Heart Disease and Ischemic Stroke
Authors: Akintunde O Akinkuolie, Julie E Buring, Paul M Ridker, Samia Mora
Journal: Circulation (2014)

Background: Enzymatically glycosylated proteins participate in multiple cellular processes, with variations in their concentration implicated in innate immunity and chronic inflammation. In addition, most inflammatory proteins are enzymatically glycosylated. GlycA is a novel nuclear magnetic resonance (NMR) biomarker whose signal originates from the N-acetyl groups of N-acetylglucosmine and N-acetylgalatosamine moieties of protein glycans. We assessed the association of GlycA with both incident CHD and ischemic stroke and performed a comparative analysis with hsCRP. Method: GlycA was quantified by proton NMR spectroscopy (LipoScience, NC) and hsCRP by immunoturbidimetric assay (Denka Seiken) in 27 649 participants of the Women’s Health Study. During a median follow up of 17 years, 1 089 incident cases of CHD and 465 incident cases of ischemic stroke were confirmed. Results: GlycA correlated with LDL cholesterol (r = 0.17), HDL cholesterol (r = -0.27), triglycerides (r = 0.47), BMI (r = 0.41) and hsCRP (r = 0.61), all p&lt;0.0001. Multivariable-adjusted HRs (95% CIs) for top versus bottom quartiles of GlycA were 1.78 (1.44-2.20) with CHD and 1.50 (1.11-2.03) with ischemic stroke respectively (p-trend for both ≤ 0.006); these associations were similar in magnitude to that obtained for hsCRP and were weakened but remained significant after adjustment for lipids. (Table) Further adjustment for hsCRP attenuated the associations which were no longer statistically significant (p-trend ≥0.40 for both CHD and ischemic stroke). Conclusion: A novel protein glycan derived biomarker, GlycA, was associated with a graded increase in the risk of both incident CHD and ischemic stroke in this prospective study of initially healthy women in a manner similar to hsCRP. Adjustment for hsCRP attenuated this association, consistent with a possible role for protein glycans in inflammation.
Employment status among low-income Caucasian and Latina breast cancer survivors
Authors: V. S. Blinder, S. Patil, A. Diamant, A. Thind, R. Maly
Journal: Journal of Clinical Oncology (2009)

6612 Background: Return to work (RTW) after breast cancer is associated with treatment recovery and quality of life. Prior research has found an 80% RTW rate in primarily Caucasian breast cancer survivors; however, little is known about the trajectory of RTW among Latinas. Qualitative research suggests that RTW is a major concern for Latinas. This study compares the rate of RTW between Latinas and Caucasians and investigates the role of job type in RTW. Methods: This is a prospective, longitudinal study of low-income, underserved breast cancer survivors who spoke English or Spanish, did not have metastatic disease, and were enrolled in the Medi-Cal Breast and Cervical Cancer Treatment Program. We interviewed survivors at 6 mos., 18 mos., and 3 yrs. after diagnosis to assess changes in employment status. The impact of independent variables including ethnicity, employment at diagnosis, job type, age, health status, and education was assessed using chi-square tests. Results: 666 survivors completed surveys at both 6 mos. and 3 yrs; 65% were Latina. The median age was 49 and 54 yrs. for Latinas and Caucasians, respectively (p &lt; 0.001). 45% of Latinas had less than a high-school education compared to 3% of Caucasians (p &lt; 0.001). The majority of Latinas worked in 3 job types: personal care-provider (23%), housekeeper (22%), and manufacturing (13%). Caucasians had greater job diversity, including clerical (15%), personal care-provider (13%), food preparer/server (12%), and sales (10%). At diagnosis, 51% of Latinas and 59% of Caucasians were employed (p = 0.07), and among these, Latinas were less likely to be working at 6 and 18 mos. than Caucasians (27% vs. 47% at 6 mos., p = 0.002 and 45% vs. 59% at 18 mos., p = 0.026). This difference dissipated by yr. 3 (53% of Latinas vs. 58% of Caucasians, p = 0.41). Job type at diagnosis was associated with RTW. Conclusions: Employed low-income Latinas and Caucasians appear to follow different RTW trajectories after breast cancer, with fewer Latinas working at 6 and 18 mos. Differences exist in job type between these populations; Caucasians have greater variation in job type and a trend toward greater likelihood of changing job type after breast cancer. This may reflect limitations in career choice among low-income Latinas and may be related to their protracted RTW trajectory. No significant financial relationships to disclose.
A randomized crossover trial of giving high-dose cisplatin with or without an overnight stay in hospital: Patients' preferences, quality of life, safety and resource use
Authors: K. Cox, R. L. O'Connell, M. R. Stockler, M. J. Boyer, P. J. Beale, R. J. Simes
Journal: Journal of Clinical Oncology (2004)

6113 Background: Treatment with high dose cisplatin (HDC) previously required an inpatient (IP) admission with an overnight stay in hospital. Improvements in supportive care mean HDC can now be given as an out-patient (OP) regimen without an overnight stay in hospital. The aim of this trial was to determine whether it is preferable to give HDC as an IP or OP regimen. Methods: Eligible patients were starting CT with 2 or more cycles or HDC (100mg or more per dose) and were suitable for treatment as an OP (adequate transport, support, telephone, no significant comorbidities). All were to have an IP cycle and an OP cycle; the order (IP or OP first) was randomly allocated. Prehydration, antiemetics and administration of HDC were identical for IP and OP. IP went home the next morning after 3L of NS over 18 hrs. OP went home the same day after 2L NS over 6 hrs, and were phoned the next morning. The primary outcome was whether patients preferred treatment as an IP or OP. Secondary outcomes included aspects of health-related quality of life rated by patients with validated scales (GLQ-8 and UBQ-C) on days 8 and 21 of each cycle . Adverse events included delays, dose reductions, elevated creatinine, and hospital readmissions. Nurses recorded their time spent with patients. Results: 59 patients were randomised: 53 had both cycles as planned, and 6 did not (4 randomized to OP first v 2 to IP first, p = .7). Most patients preferred OP to IP treatment (36 v 13, p = .002); 40 wanted their next cycle as an OP (p < .0001). There were no significant differences in patients' ratings of nausea, vomiting, fatigue, anxiety, depression or overall quality of life. Adverse events were few and unrelated to IP v OP administration (respective numbers): delayed cycles (4 v 5), dose reductions (1 v 0), and hospital readmissions (9 v 7). Nursing time was longer for IP than OP (163 v 104 minutes, p < .001). Conclusions: Giving HDC as an OP regimen without an overnight stay in hospital was preferred by most patients (but not all), appeared safe, and used less resources. No significant financial relationships to disclose.