tbuckley/cabot-search huggingface dataset:
AIDS-Related Malignancies: the Emerging Epidemic
Authors: A M Levine
Journal: JNCI Journal of the National Cancer Institute (1993)

The incidence of three malignancies has increased in conjunction with the epidemic of human immunodeficiency virus (HIV) disease, and they are currently considered acquired immunodeficiency syndrome (AIDS)-defining conditions. These are Kaposi's sarcoma, associated with AIDS since the onset of the epidemic in 1981; intermediate or high-grade B-cell lymphoma, which became AIDS-defining in 1985; and cervical carcinoma in HIV-infected women, formally recognized as an AIDS-defining diagnosis on January 1, 1993. Approximately 40% of all patients with AIDS have developed cancer during the course of HIV infection. Further, as survival has improved in HIV disease, the incidence of these malignancies has increased. It is thus expected that greater numbers of patients with AIDS-related lymphoma and cervical cancer will be diagnosed in the years ahead. The epidemiologic factors associated with neoplastic disease differ among patients with the three AIDS-related malignancies. The pathogenesis of neoplastic disease also differs. The specific etiologic steps in the development of AIDS-related Kaposi's sarcoma and lymphoma are currently unknown. However, a great deal of information has already been acquired, which may have bearing on the pathogenesis of malignant disease in general, as well as the elucidation of future therapeutic modalities. The specific epidemiologic, etiologic, and clinical characteristics of the AIDS-related malignancies will be described herein. It is hoped that this review will serve to outline our current understanding of this area, to introduce the questions and controversies which are apparent in the field, and to mention those areas in which future research might be focused.
561 FACTORS PREDICTIVE OF TOLERANCE AFTER LIVER TRANSPLANTATION
Authors: R. García de la Garza, P. Sarobe, J. Merino, J.J. Lasarte, D. DÄvola, V. Belsue, J.A. Delgado, L. Silva, M. Iñarrairaegui, B. Sangro, I. Sola, F. Pardo, J. Quiroga, J.I. Herrero
Journal: Journal of Hepatology (2013)
Aquaporin-2 transfection of Madin-Darby canine kidney cells reconstitutes vasopressin-regulated transcellular osmotic water transport.
Authors: P M Deen, J P Rijss, S M Mulders, R J Errington, J van Baal, C H van Os
Journal: Journal of the American Society of Nephrology (1997)

Water transport across the mammalian collecting tubule is regulated by vasopressin-dependent aquaporin-2 insertion into and retrieval from the apical cell membrane. To establish a cell line that properly expresses aquaporin-2 and its hormone-dependent shuttling, Madin-Darby canine kidney cells were stably transfected with an aquaporin-2 expression construct. Cells of a representative clone (wild-type 10 [WT-10]) were grown on semipermeable supports, and transcellular osmotic water permeability (Pf; in microm/s +/- SEM) was measured. The basal Pf of WT-10 cells, which was lowered with indomethacin, increased from 10.6 +/- 0.8 to 35.7 +/- 1.2 upon incubation with 1-desamino-8-D-arginine vasopressin (dDAVP). This increase coincided with the translocation of aquaporin-2 from an intracellular compartment to the apical membrane. The Pf of untransfected cells (6.5 +/- 0.8) was unchanged by dDAVP. Kinetic studies with WT-10 cells revealed that maximal Pf was obtained within 30 min after dDAVP addition, which remained elevated for at least 90 min. Intracellular cAMP levels peaked within 5 min after dDAVP admission and decreased to basal levels within 45 min. After preincubation with dDAVP, the Pf decreased within 15 min after dDAVP washout and returned to basal levels within 75 min. In conclusion, the WT-10 cells mimic the vasopressin-regulated transcellular water transport and aquaporin-2 translocation as found in collecting duct cells to a great extent, and therefore constitute an in vitro cell model that can be used to study the regulation of transcellular water transport in detail and provide a simplified test system for screening putative aquaporin-2 blockers.
Biology-Driven Phase II Trials: What Is the Optimal Model for Molecular Selection?
Authors: Fabrice Andre, Suzette Delaloge, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2011)

The number of newly discovered oncogenic molecular alterations has increased dramatically during recent years. A large number of such relevant oncogenic molecular alterations occur in a small percentage of patients and define a specific segment of the disease. Disease segmentation in rare molecular entities is also related to a combination of frequent events. For example, ERBB2 amplification and PIK3CA mutations coexist in about 2% of breast cancers and could define a trastuzumab-resistant phenotype. Overall, this introduction emphasizes that each frequent cancer type could, in fact, be subdivided into several rare molecular diseases according to relevant oncogenic events. This segmentation into rare molecular diseases may have major implications for early drug development.
Guided Medication Dosing for Inpatients With Renal Insufficiency
Authors: G M Chertow, J Lee, G J Kuperman, E Burdick, J Horsky, D L Seger, R Lee, A Mekala, J Song, A L Komaroff, D W Bates
Journal: JAMA (2001)

Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error.To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes.Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital.Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed.Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods.A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization.Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.
Lack of plasma interleukin-1 beta or tumor necrosis factor-alpha elevation during unfavorable hemodialysis conditions.
Authors: A C Powell, L E Bland, C W Oettinger, S K McAllister, J C Oliver, M J Arduino, M S Favero
Journal: Journal of the American Society of Nephrology (1991)

Plasma interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were determined by ELISA in 17 healthy controls, 23 HD patients, 10 continuous ambulatory peritoneal dialysis patients, and 15 chronic renal failure patients, as well as in 2 HD patients experiencing pyrogenic reactions. Another group of 10 chronic HD patients were dialyzed for 2.5 h, 5 with first-use Cuprophan membranes and 5 with first-use high-flux cellulose triacetate membranes. The mean bacterial and endotoxin concentrations of the dialysate used for HD treatments during the study period were 18,440 +/- 530 CFU/mL (mean +/- SEM) and 976 +/- 205 pg/mL, respectively. Blood specimens were obtained intradialysis and postdialysis for cytokine assay and were incubated to augment cytokine production. There was no difference in plasma IL-1 beta or TNF-alpha concentrations among the healthy controls, continuous ambulatory peritoneal dialysis patients, chronic renal failure patients, or HD patients. Neither cytokine increased significantly during or after HD. Two patients experiencing pyrogenic reactions had plasma TNF-alpha concentrations of 537 and 413 pg/mL, compared with matched controls of 6 and 0 pg/mL. Il-1 beta concentration did not differ from controls. We conclude that: (1) plasma IL-1 beta and TNF-alpha are not chronically elevated in chronic renal failure, continuous ambulatory peritoneal dialysis, or HD patients; (2) HD with new Cuprophan or cellulose triacetate membranes and high concentrations of dialysate endotoxin and bacteria does not cause elevation of circulating IL-1 beta or TNF-alpha; and (3) pyrogenic reactions might be mediated by TNF-alpha.
Polio Eradication From the Western Hemisphere
Authors: Ciro A. de Quadros, Jon K. Andrus, Jean-Marc Olive, Carlyle Guerra de Macedo, Donald A. Henderson
Journal: Annual Review of Public Health (1992)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More
Circulating tumor cells versus tumor-derived cell-free DNA: rivals or partners in cancer care in the era of single-cell analysis?
Authors: Evelyn Kidess, Stefanie S Jeffrey
Journal: Genome Medicine (2013)

Cancer presents a problem of complexity. Although our understanding of tumor biology has increased expo nen­ tially over recent decades, and we have many available technologies to characterize tumors, whether and when an individual cancer will metastasize remains unknown. Moreover, if metastases do occur, their molecular features may not match those of the primary tumor or other metastases. Ideally, to guide treatment decisions, all micro­ and macrometastases would be identifi ed, biopsied and molecularly analyzed, but this is not currently possible, practical or safe. Th us, investigations are now focusing on blood­based assays that detect and characterize circulating tumor cells or circulating tumor DNA (a component of cell­free DNA). Th ese minimally invasive, real­time ‘liquid biopsies’ can be performed at multiple intervals to monitor disease and tailor cancer therapy. It is as yet unknown whether these represent com­ peting technologies or if they should be used together. Tumors are heterogeneous and tend to change over
Adjunctive Antipsychotic Prescriptions for Outpatients with Depressive Disorders in Asia: The Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) Study
Authors: Seon-Cheol Park, Naotaka Shinfuku, Margarita M Maramis, Min-Soo Lee, Yong Chon Park
Journal: American Journal of Psychiatry (2015)
Serotonin 5-HT3 Receptor Antagonist for Treatment of Severe Diabetic Diarrhea
Authors: Satoshi Murao, Hitoshi Hosokawa
Journal: Diabetes Care (2010)

Diabetic diarrhea is a troublesome gastrointestinal complication of diabetes. This condition persists for several weeks to months, and it frequently accompanies fecal incontinence. The cause of diabetic diarrhea is not fully understood, but autonomic neuropathy is thought to be an underlying mechanism (1). Parenteral somatostatin analog octreotide has been shown to be useful in the treatment of severe long-standing diabetic diarrhea (1). Selective serotonin 5-hydroxy tryptamine type 3 (HT3) receptor antagonist, which was developed as an antiemetic in cancer chemotherapy, prolongs colonic transit, inhibits small bowel secretion, and decreases colonic compliance (2). Here, we report the underlying mechanism of ramosetron (2 …
TBCRC 001: Randomized Phase II Study of Cetuximab in Combination With Carboplatin in Stage IV Triple-Negative Breast Cancer
Authors: Lisa A. Carey, Hope S. Rugo, P. Kelly Marcom, Erica L. Mayer, Francisco J. Esteva, Cynthia X. Ma, Minetta C. Liu, Anna Maria Storniolo, Mothaffar F. Rimawi, Andres Forero-Torres, Antonio C. Wolff, Timothy J. Hobday, Anastasia Ivanova, Wing-Keung Chiu, Madlyn Ferraro, Emily Burrows, Philip S. Bernard, Katherine A. Hoadley, Charles M. Perou, Eric P. Winer
Journal: Journal of Clinical Oncology (2012)

Epidermal growth factor receptor (EGFR) is a targetable receptor frequently overexpressed in basal-like breast cancer, which comprises most triple-negative breast cancers (TNBCs), the only subtype without established targeted therapy.In this randomized phase II trial, patients with metastatic TNBC received anti-EGFR antibody cetuximab (400 mg/m(2) load then 250 mg/m(2) per week intravenously [IV]) alone, with carboplatin (area under the curve of 2, once per week IV) added after progression or as concomitant therapy from the beginning. Response rate (RR) was the primary end point; others included time to progression (TTP), overall survival (OS), and toxicity. Embedded correlative studies included molecular subtyping on archival tissue. Fresh tumor tissue before and after 7 to 14 days of therapy was used for microarray analyses exploring EGFR pathway activity and inhibition.In 102 patients with TNBC, RRs were 6% (two of 31) to cetuximab and 16% (four of 25) to cetuximab plus carboplatin after progression. RR to those treated from the beginning with cetuximab plus carboplatin was 17% (12 of 71); 31% of patients responded or had prolonged disease stabilization. The cetuximab plus carboplatin regimen was well tolerated, but both TTP and OS were short at 2.1 months (95% CI, 1.8 to 5.5 months) and 10.4 months (95% CI, 7.7 to 13.1 months), respectively. Of 73 patients with archival tissue for analysis, 74% had basal-like molecular subtype. Sixteen patients had tumor biopsies before and 1 week after therapy; genomic patterns of the EGFR pathway showed activation in 13 and inhibition by therapy in five.Despite strong preclinical data, combination cetuximab plus carboplatin in metastatic TNBC produced responses in fewer than 20% of patients. EGFR pathway analysis showed that most TNBCs involved activation. However, cetuximab blocked expression of the EGFR pathway in only a minority, suggesting that most had alternate mechanisms for pathway activation.
Effects of Candesartan on the Development of a New Diagnosis of Diabetes Mellitus in Patients With Heart Failure
Authors: Salim Yusuf, Jan B. Ostergren, Hertzel C. Gerstein, Marc A. Pfeffer, Karl Swedberg, Christopher B. Granger, Bertil Olofsson, Jeffrey Probstfield, John V. McMurray
Journal: Circulation (2005)

Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan (an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Program).We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan (target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group (hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to 0.96; P=0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR, 0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28).The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.
Examination of the Carbon Monoxide Diffusing Capacity (D<scp>l</scp><sub>CO</sub>) in Relation to Its K<scp>co</scp>and V<scp>a</scp>Components
Authors: J. Michael B. Hughes, Neil B. Pride
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The single-breath carbon monoxide diffusing capacity (DL(CO)) is the product of two measurements during breath holding at full inflation: (1) the rate constant for carbon monoxide uptake from alveolar gas (kco [minute(-1)]) and (2) the "accessible" alveolar volume (Va). kco expressed per mm Hg alveolar dry gas pressure (Pb*) as kco/Pb*, and then multiplied by Va, equals Dl(CO); thus, Dl(CO) divided by Va (DL(CO)/Va, also called Kco) is only kco/Pb* in different units, remaining, essentially, a rate constant. The notion that DL(CO)/Va "corrects" DL(CO) for reduced Va is physiologically incorrect, because DL(CO)/Va is not constant as Va changes; thus, the term Kco reflects the physiology more appropriately. Crucially, the same DL(CO) may occur with various combinations of Kco and Va, each suggesting different pathologies. Decreased Kco occurs in alveolar-capillary damage, microvascular pathology, or anemia. Increased Kco occurs with (1) failure to expand normal lungs to predicted full inflation (extrapulmonary restriction); or (2) increased capillary volume and flow, either globally (left-to-right intracardiac shunting) or from flow and volume diversion from lost or damaged units to surviving normal units (e.g., pneumonectomy). Decreased Va occurs in (1) reduced alveolar expansion, (2) alveolar damage or loss, or (3) maldistribution of inspired gases with airflow obstruction. Kco will be greater than 120% predicted in case 1, 100-120% in case 2, and 40-120% in case 3, depending on pathology. Kco and Va values should be available to clinicians, as fundamental to understanding the clinical implications of DL(CO). The diffusing capacity for nitric oxide (DL(NO)), and the DL(NO)/DL(CO) ratio, provide additional insights.
Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability
Authors: Qi Xue, Benjamin Hopkins, Carole Perruzzi, Durga Udayakumar, David Sherris, Laura E. Benjamin
Journal: Cancer Research (2008)

Abstract It has become clear that the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is central for promoting both tumor and tumor stroma and is therefore a major target for anticancer drug development. First- and second-generation rapalogs (prototypical mTOR inhibitors) have shown promise but, due to the complex nature of mTOR signaling, can result in counterproductive feedback signaling to potentiate upstream Akt signaling. We present a novel PI3K/Akt/mTOR inhibitor, Palomid 529 (P529), which inhibits the TORC1 and TORC2 complexes and shows both inhibition of Akt signaling and mTOR signaling similarly in tumor and vasculature. We show that P529 inhibits tumor growth, angiogenesis, and vascular permeability. It retains the beneficial aspects of tumor vascular normalization that rapamycin boasts. However, P529 has the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells. [Cancer Res 2008;68(22):9551–7]
Sponsorship, Authorship, and Accountability
Authors: Frank Davidoff
Journal: JAMA (2001)

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Long-Term Effects of the Booster-Enhanced READY-Girls Preconception Counseling Program on Intentions and Behaviors for Family Planning in Teens With Diabetes
Authors: Denise Charron-Prochownik, Susan M. Sereika, Dorothy Becker, Neil H. White, Patricia Schmitt, A. Blair Powell, Ana Maria Diaz, Jacquelyn Jones, William H. Herman, Andrea F. Rodgers Fischl, Laura McEwen, Monica DiNardo, Feng Guo, Julie Downs
Journal: Diabetes Care (2013)

OBJECTIVE To examine 12-month effects of a booster-enhanced preconception counseling (PC) program (READY-Girls) on family planning for teen girls with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Participants 13–19 years of age (n = 109) were randomized to a standard care control group (CG) or intervention group (IG) that received PC over three consecutive clinic visits. Prepost data were collected at baseline, 3- and 6-month booster sessions, and a 12-month follow-up visit. RESULTS Mean age was 15.8 years; 9 (8%) subjects had type 2 diabetes; and 18 (17%) subjects were African American. At baseline, 20% (n = 22 of 109) had been sexually active, and of these, 50% (n = 11) had at least one episode of unprotected sex. Over time, IG participants retained greater PC knowledge (F[6, 541] = 4.05, P = 0.0005) and stronger intentions regarding PC (significant group-by-time effects) especially after boosters. IG participants had greater intentions to discuss PC (F[6, 82.4] = 2.56, P = 0.0254) and BC (F[6, 534] = 3.40, P = 0.0027) with health care providers (HCPs) and seek PC when planning a pregnancy (F[6, 534] = 2.58, P = 0.0180). Although not significant, IG participants, compared with CG, showed a consistent trend toward lower rates of overall sexual activity over time: less sexual debut (35 vs. 41%) and higher rates of abstinence (44 vs. 32%). No pregnancies were reported in either group throughout the study. CONCLUSIONS READY-Girls appeared to have long-term sustaining effects on PC knowledge, beliefs, and intentions to initiate discussion with HCPs that could improve reproductive health behaviors and outcomes. Strong boosters and providing PC at each clinic visit could play important roles in sustaining long-term effects.