tbuckley/cabot-search huggingface dataset:
Aplastic anemia after liver transplantation for fulminant viral hepatitis: Black boX or bag of worms?
Authors: Jerome B. Zeldis
Journal: Hepatology (1989)

Aplastic anemia developed in 9 of 32 patients (28 percent) undergoing orthotopic liver transplantation for acute non-A, non-B hepatitis, at one to seven weeks after the procedure. No patient previously had evidence of hematologic dysfunction or conditions known to be associated with aplastic anemia. No other cases of aplastic anemia were identified among 1463 patients undergoing liver transplantation for all other indications at the four centers participating in the study (chi-square = 415, P &lt; 0.001; 95 percent confidence interval for the incidence of aplastic anemia after transplantation for non-A, non-B hepatitis, 13 to 44 percent, vs. 0.00 to 0.13 percent for all other indications). The operative and postoperative treatment of these patients was not otherwise different, indicating that the aplastic anemia was a complication of the hepatitis, not of the transplantation proce- dure. Four of the nine patients died of complications due to infections. Three of the surviving patients have been followed for less than six months, one for one year, and one for two years. The two patients followed the longest have recovered marrow function to an appreciable degree, and two of the others have evidence of early recovery. We concluded that patients undergoing ortho-topic liver transplantation for non-A, non-B hepatitis are at a high risk for the development of aplastic anemia.
Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial
Authors: Nicole MA Krekel, Max H Haloua, Alexander MF Lopes Cardozo, Roos H de Wit, Anne Marie Bosch, Louise M de Widt-Levert, Sandra Muller, Henk van der Veen, Elisabeth Bergers, Elly SM de Lange de Klerk, Sybren Meijer, M Petrousjka van den Tol
Journal: The Lancet Oncology (2012)
Altered calcium handling in left ventricular pressure-overload hypertrophy as detected with aequorin in the isolated, perfused ferret heart.
Authors: L A Bentivegna, L W Ablin, Y Kihara, J P Morgan
Journal: Circulation Research (1991)

The purpose of this study was to test the hypothesis that systolic and diastolic dysfunction in left ventricular pressure-overload hypertrophy is caused by abnormal intracellular calcium handling. Experiments were performed with intact, buffer-perfused, isovolumic ferret hearts (n = 9 hypertrophied, n = 9 control) that were loaded with the bioluminescent indicator aequorin to monitor changes in cytoplasmic calcium. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Compared with their age-matched controls, significant hypertrophy of the left ventricle developed 4 weeks after postvalvular aortic banding; at the time the animals were killed, the left ventricular weight/body weight ratio was increased in the banded animals (5.3 x 10(-3) versus 3.6 x 10(-3), p less than 0.001). As indicated by the diastolic pressure-volume relation, left ventricular distensibility was significantly diminished in the hypertrophied hearts. In comparison to the controls, the hypertrophied hearts demonstrated a prolonged duration of isovolumic contraction (time to 90% decline from peak: 278 +/- 5.4 versus 247 +/- 10.2 msec, p less than 0.05), but a marked decrease in peak systolic midwall stress (22.4 +/- 5.0 versus 38.6 +/- 5.7 g/cm2, p less than 0.05). The increased duration of isovolumic contraction correlated with a similar prolongation of the calcium transient (time to 90% decline from peak: 245 +/- 19.5 versus 127 +/- 13.2 msec, p less than 0.05), indicating that the rate of sequestration and perhaps release of calcium by the sarcoplasmic reticulum is decreased in hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of putative targets of immunotherapy in acute myeloid leukemia and healthy tissues
Authors: M Goswami, N Hensel, B D Smith, G T Prince, L Qin, H I Levitsky, S A Strickland, M Jagasia, B N Savani, J W Fraser, H Sadrzadeh, T Rajkhowa, S Ito, N A Jain, M Battiwalla, A T Fathi, M J Levis, A J Barrett, C S Hourigan
Journal: Leukemia (2014)

inhibitor (ibrutinib) or PI3Kd inhibitor (CAL-101) results in increased resistance to antitumor activity of anti-CD20 mAbs.Current study demonstrates that BCR inhibitors strongly downregulate CD20 expression in tumor cells, leading to decreased binding of anti-CD20 mAbs to the surface of tumor cells and impairment of CDC and ADCC mechanisms that mediate antitumor effects of anti-CD20 mAbs in vivo.Our observations strongly imply that before investigating novel therapeutic combinations in cancer patients, extensive preclinical studies should be carried out to evaluate possible interactions between drugs at the molecular level.
Velcade and Vitamin C: Too Much of a Good Thing?
Authors: Laurence Catley, Kenneth C. Anderson
Journal: Clinical Cancer Research (2006)

In this issue, Zou et al. report that vitamin C abrogated the ability of bortezomib (PS-341, Velcade) to induce apoptosis, G2-M arrest, and cleavage of caspase 8, caspase 3, and poly(ADP-ribose) polymerase and to augment tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis
Relationship of High and Low Ankle Brachial Index to All-Cause and Cardiovascular Disease Mortality
Authors: Helaine E. Resnick, Robert S. Lindsay, Mary McGrae McDermott, Richard B. Devereux, Kristina L. Jones, Richard R. Fabsitz, Barbara V. Howard
Journal: Circulation (2004)

Background— The associations of low (&lt;0.90) and high (&gt;1.40) ankle brachial index (ABI) with risk of all-cause and cardiovascular disease (CVD) mortality have not been examined in a population-based setting. Methods and Results— We examined all-cause and CVD mortality in relation to low and high ABI in 4393 American Indians in the Strong Heart Study. Participants had bilateral ABI measurements at baseline and were followed up for 8.3±2.2 years (36 589 person-years). Cox regression was used to quantify mortality rates among participants with high and low ABI relative to those with normal ABI (0.90 ≤ABI ≤1.40). Death from all causes occurred in 1022 participants (23.3%; 27.9 deaths per 1000 person-years), and of these, 272 (26.6%; 7.4 deaths per 1000 person-years) were attributable to CVD. Low ABI was present in 216 participants (4.9%), and high ABI occurred in 404 (9.2%). Diabetes, albuminuria, and hypertension occurred with greater frequency among persons with low (60.2%, 44.4%, and 50.1%) and high (67.8%, 49.9%, and 45.1%) ABI compared with those with normal ABI (44.4%, 26.9%, and 36.5%), respectively ( P &lt;0.0001). Adjusted risk estimates for all-cause mortality were 1.69 (1.34 to 2.14) for low and 1.77 (1.48 to 2.13) for high ABI, and estimates for CVD mortality were 2.52 (1.74 to 3.64) for low and 2.09 (1.49 to 2.94) for high ABI. Conclusions— The association between high ABI and mortality was similar to that of low ABI and mortality, highlighting a U-shaped association between this noninvasive measure of peripheral arterial disease and mortality risk. Our data suggest that the upper limit of normal ABI should not exceed 1.40.
Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone
Authors: Amil M. Shah, Brian Claggett, Nancy K. Sweitzer, Sanjiv J. Shah, Inder S. Anand, Li Liu, Bertram Pitt, Marc A. Pfeffer, Scott D. Solomon
Journal: Circulation (2015)

Impairment in left ventricular systolic function has been described in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether left ventricular longitudinal strain (LS) is predictive of cardiovascular outcomes in HFpEF beyond clinical and conventional echocardiographic measures.
Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases
Authors: T. de Baère, A. Aupérin, F. Deschamps, P. Chevallier, Y. Gaubert, V. Boige, M. Fonck, B. Escudier, J. Palussiére
Journal: Annals of Oncology (2015)

Minimal invasive methods are needed as an alternative to surgery for treatment of lung metastases.The prospective database of two cancer centers including all consecutive patients treated with radiofrequency ablation (RFA) for lung metastasis over 8 years was reviewed. RFA was carried out under general anesthesia, with computed tomography guidance using a 15-gauge multitined expandable electrodes RF needle.Five hundred sixty-six patients including 290 men (51%), 62.7 ± 13.2 years old with primary tumor to the colon (34%), rectum (18%), kidney (12%), soft tissue (9%) and miscellaneous (27%) received 642 RFA for 1037 lung metastases. Fifty-three percent of patients had 1 metastasis, 25% had 2, 14% had 3, 5% had 4 and 4% had 5-8. Metastases were unilateral (75%), or bilateral (25%). The median diameter [extremes] of metastases was 15 mm (4-70). Twenty-two percent of patients had extrapulmonary disease amenable to local therapy including 49 liver, 16 bone and 60 miscellaneous metastases. Median follow-up was 35.5 months. Median overall survival (OS) was 62 months. Four-year local efficacy was 89%. Four-year lung disease control rate was 44.1%, with patient retreated safely up to four times. Primary origin, disease-free interval, size and number of metastases were associated with OS in multivariate analysis. Progression at RFA site was associated with poor OS [P = 0.011, hazard ratio (HR): 1.69 (95% confidence interval 1.13-2.54)]. In the 293 colorectal cancer metastases, size >2 cm (HR = 2.10, P = 0.0027) and a number of metastases ≥3 (HR = 1.86, P = 0.011) remained significantly associated with OS. A prognostic score made of three groups based on the four above-mentioned prognostic factors demonstrated 3-year OS rates of respectively 82.2%, 69.5% and 53.6% (log-rank test, P ≤ 0.0001) among the three groups in the overall population, and of 81.3%, 72.8% and 57.9% (log-rank test, P = 0.005) in the colorectal cancer patients.Radiofrequency is an option for treatment of small size lung metastases, namely the ones below 2-3 cm.
The Cross-Validated Adaptive Signature Design
Authors: Boris Freidlin, Wenyu Jiang, Richard Simon
Journal: Clinical Cancer Research (2010)

Many anticancer therapies benefit only a subset of treated patients and may be overlooked by the traditional broad eligibility approach to design phase III clinical trials. New biotechnologies such as microarrays can be used to identify the patients that are most likely to benefit from anticancer therapies. However, due to the high-dimensional nature of the genomic data, developing a reliable classifier by the time the definitive phase III trail is designed may not be feasible.Previously, Freidlin and Simon (Clinical Cancer Research, 2005) introduced the adaptive signature design that combines a prospective development of a sensitive patient classifier and a properly powered test for overall effect in a single pivotal trial. In this article, we propose a cross-validation extension of the adaptive signature design that optimizes the efficiency of both the classifier development and the validation components of the design.The new design is evaluated through simulations and is applied to data from a randomized breast cancer trial.The cross-validation approach is shown to considerably improve the performance of the adaptive signature design. We also describe approaches to the estimation of the treatment effect for the identified sensitive subpopulation.
ET-25 * THERAPEUTIC MODULATION OF MDM2 IN NEUROBLASTOMA
Authors: K. Kania, K. Pollok, L. Gelbert, H. Shannon, B. Bailey, C. Batuello
Journal: Neuro-Oncology (2014)

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In high-risk NB, the MYCN gene is amplified in approximately 25% of all cases, and is considered to be a negative prognostic factor. MYCN can transcriptionally activate the murine double minute-2 (MDM2) gene, leading to increased expression of MDM2, downregulation of the tumor suppressor p53, and increased tumorigenesis. To improve treatment outcome in NB, inhibition of MDM2 function with front-line chemotherapy is being explored. The E3 ubiquitin ligase, MDM2, which ubiquitinates and targets p53 for proteosomal degradation, is a multifunctional protein that regulates the p53 signaling network and the DNA damage response. Cell growth assays indicate that inhibition of MDM2 function by the small molecule antagonist nutlin3a is synergistic to additive in combination with frontline chemotherapeutics in IMR32 NB cells (wt p53, MYCN amplified). To determine the effects of the combination of nutlin3a and cisplatin on a cell line without MYCN amplification, cell growth assays using SK-N-SH NB cells (wt p53, single MYCN copy) were performed. Results demonstrated that combined treatment with nutlin3a and cisplatin is synergistic in SK-N-SH NB cells. To delineate the mechanism of action in IMR32 cells exposed to cisplatin and nutlin3a, the impact of the two drugs, alone and in combination, was investigated in the context of MDM2 expression, modulation of the cell cycle, and DNA damage response. Western blot analyses were performed to monitor expression of cell cycle proteins and DNA damage/repair responses that we hypothesized are regulated by nutlin3a-mediated MDM2 blockade. Results demonstrated that combination treatment in IMR32 NB cells enhanced the DNA damage response and inhibited cell growth. The data provide further support for the hypothesis that MDM2 is a target that can be therapeutically exploited in combination with front-line chemotherapy to improve treatment outcome in MYCN non-amplified and MYCN amplified neuroblastoma.
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Authors: Stephan A. Grupp, Michael Kalos, David Barrett, Richard Aplenc, David L. Porter, Susan R. Rheingold, David T. Teachey, Anne Chew, Bernd Hauck, J. Fraser Wright, Michael C. Milone, Bruce L. Levine, Carl H. June
Journal: New England Journal of Medicine (2013)

Chimeric antigen receptor-modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre-B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×10(6) to 1.2×10(7) CTL019 cells per kilogram of body weight. In both patients, CTL019 T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. In addition, the chimeric antigen receptor T cells were observed in the cerebrospinal fluid (CSF), where they persisted at high levels for at least 6 months. Eight grade 3 or 4 adverse events were noted. The cytokine-release syndrome and B-cell aplasia developed in both patients. In one child, the cytokine-release syndrome was severe; cytokine blockade with etanercept and tocilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce antileukemic efficacy. Complete remission was observed in both patients and is ongoing in one patient at 11 months after treatment. The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. Chimeric antigen receptor-modified T cells are capable of killing even aggressive, treatment-refractory acute leukemia cells in vivo. The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL.
Diabetes in urban African-Americans. XIX. Prediction of the need for pharmacological therapy.
Authors: L M Thaler, D C Ziemer, I M El-Kebbi, D L Gallina, C B Cook, L S Phillips
Journal: Diabetes Care (2000)

OBJECTIVE: To develop a prediction rule that will identify patients who will require pharmacological therapy within 6 months of first presentation to a diabetes clinic. RESEARCH DESIGN AND METHODS: Among the patients who came to the Grady Diabetes Clinic between 1991 and 1997, we randomized 557 frequent attenders to a development group and 520 frequent attenders to a validation group. Using multiple logistical regression, we derived a prediction rule in the development group to project whether patients would require pharmacological intervention to achieve HbA1c levels &amp;lt;7% after 6 months. The utility of the prediction rule was then confirmed in the validation group and tested prospectively on an additional group of 93 patients who presented from 1997 to 1998. Performance of the prediction rule was assessed using receiver operating characteristic (ROC) curves. RESULTS: The rule (-4.469 + 1.932 x sulfonylurea Rx + 1.334 x insulin Rx + 0.196 x duration + 0.468 x fasting glucose, where "Rx" indicates a prescription) predicted the need for pharmacological intervention in the development group (P &amp;lt; 0.0001). Use of insulin or sulfonylurea therapy at presentation, duration of diabetes, and fasting glucose levels were significant predictors of the future need for pharmacological management. The prediction rule also performed well in the validation group (positive predictive value 90%, correlation between predicted and observed need for medical management 0.99). ROC curves confirmed the value of the prediction rule (area under the curves was 0.91 for the development group, 0.85 for the validation group, and 0.81 for the prospective group). CONCLUSIONS: Early identification of individuals who will require pharmacological intervention to achieve national standards for glycemic control can be achieved with high probability, thus allowing for more efficient management of diabetes.
Higher Intakes of Fish Protein Are Related to a Lower Risk of Microalbuminuria in Young Swedish Type 1 Diabetic Patients
Authors: Anna V. Möllsten, Gisela G. Dahlquist, Eva-Lena Stattin, Susanne Rudberg
Journal: Diabetes Care (2001)

OBJECTIVE—To examine the influence of dietary intake from various protein and fat sources on the occurrence of microalbuminuria in type 1 diabetic patients. RESEARCH DESIGN AND METHODS—In this nested case control study, 1,150 patients with diabetes duration &amp;gt;5 years reported dietary habits for the previous 12 months and submitted urinary samples for the analysis of albumin excretion rate (AER). A total of 75 cases of albuminuria (overnight AER ≥15 μg/min) were identified and compared with 225 duration-matched control subjects. RESULTS—Neither mean protein, fat intake, average fish protein intake (control subjects 4.56 ± 3.83 g/day and cases 3.82 ± 2.87 g/day; P = 0.12), nor intake of meat and vegetable protein differed between the cases of albuminuria and the control subjects. High consumers of fish protein (greater than the 75th percentile) (12 cases and 63 control subjects, mean intake 9.35 g fish protein/day, i.e., ∼53 g fish/day) had lower odds ratios (ORs) for microalbuminuria than individuals consuming less fish protein (mean 2.72 g/day) (crude OR 0.49 and 95% CI 0.25–0.97). When adjusted for known confounding factors, such as HbA1c, mean arterial pressure, diabetes duration, age, sex, smoking, BMI, country region, and total energy, individuals with a high intake of fish protein and fish fat showed a reduction in the risk for microalbuminuria (OR 0.22 and 0.31, respectively; 95% CI 0.09–0.56 and 0.13–0.76, respectively). When fish protein and fat were adjusted for each other, a high intake of fish protein but not of fish fat was still significantly associated with a decrease in the risk for microalbuminuria. CONCLUSIONS—Total protein and fat intake were not associated with the presence of microalbuminuria, but a diet including a high amount of fish protein seemed to lessen the risk.
Evolved Tumor Suppression: Why Are We So Good at Not Getting Cancer?
Authors: James DeGregori
Journal: Cancer Research (2011)

The law of natural selection can be used to understand cancer development at the level of species as well as at the level of cells and tissues. Through this perspective, I seek to explain: (i) Why the lack of sufficient selective pressure to prevent cancers in old age helps explain the exponential increase in cancer incidence in the elderly. (ii) Why the evolution of long-lived animals necessitated the acquisition of potent tumor suppressive mechanisms. (iii) How the requirement to prevent inappropriate somatic cell expansion and cancer has constrained developmental and tissue architectural modalities. (iv) How the evolution of well-adapted stem cells with complex niche requirements has conferred resistance to oncogenic mutations, as phenotype-altering genetic change is almost always disadvantageous within a well-adapted cell population. (v) How the impairment of stem cell fitness, as occurs in old age, can promote selection for adaptive mutations and cancer initiation. (vi) Why differential maintenance of stem cell fitness may explain how different vertebrate species with enormous differences in life span and body size similarly avoid cancer through reproductive years.
Ethnic Differences in Perinatal Outcome of Gestational Diabetes Mellitus
Authors: Jana Kaida Silva, Joseph Keawe‘aimoku Kaholokula, Robert Ratner, Marjorie Mau
Journal: Diabetes Care (2006)

Despite the high rates of gestational diabetes mellitus (GDM) among certain Pacific Islander and Asian ethnic groups in the U.S., little is known about the risk for adverse perinatal outcomes in these populations. We sought to examine ethnic differences in perinatal outcome among Asian and Pacific-Islander women with GDM.A retrospective review of all women referred to the largest outpatient GDM program in the state of Hawai'i from 1995 to 2005 was conducted. Patients of Native-Hawaiian/Pacific-Islander, Japanese, Chinese, Filipino, and Caucasian ethnicity were included (n = 2,155). Treatment of all patients consisted of an outpatient education class, dietary management, self-monitoring of blood glucose, and insulin instruction (if indicated). Demographics, maternal and neonatal characteristics, and delivery information were evaluated.Neonates born to Native-Hawaiian/Pacific-Islander mothers and Filipino mothers had 4 and 2 times the prevalence of macrosomia, respectively, compared with neonates born to Japanese, Chinese, and Caucasian mothers. These differences persisted after adjustment for other statistically significant maternal and fetal characteristics. Ethnic differences were not observed for other neonatal or maternal complications associated with GDM, with the exception of neonatal hypoglycemia and hyperbilirubinemia.Significant ethnic differences in perinatal outcomes exist across Asian and Pacific-Islander women with GDM. This finding emphasizes the need to better understand ethnic-specific factors in GDM management and the importance of developing ethnic-tailored GDM interventions to address these disparities.