tbuckley/cabot-search huggingface dataset:
Recombinant Vascular Endothelial Growth Factor Secreted From Tissue-Engineered Bioartificial Muscles Promotes Localized Angiogenesis
Authors: Yongxin Lu, Janet Shansky, Michael Del Tatto, Paulette Ferland, Xiaoyun Wang, Herman Vandenburgh
Journal: Circulation (2001)

Background Therapeutic angiogenesis by the administration of recombinant vascular endothelial growth factor (rVEGF) is a novel strategy for the treatment of ischemic disorders. rVEGF has been delivered as a protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. In the present study, we examined a new method for delivery of rVEGF using implantable bioartificial muscle (BAM) tissues made from genetically modified primary skeletal myoblasts. Our goal was to determine whether the rVEGF delivered by this technique promoted controlled angiogenesis in nonischemic and/or ischemic adult mouse tissue. Methods and Results Primary adult mouse myoblasts were retrovirally transduced to secrete human or mouse rVEGF and tissue-engineered into implantable 1×10 to 15-mm BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 290 to 511 ng of bioactive mouse or human VEGF/BAM per day. rVEGF BAMs implanted subcutaneously into syngeneic mice caused a 30-fold increase in the number of CD31-positive capillary cells within the BAM by 1 week compared with control BAMs. Implantation of rVEGF-secreting BAMs into ischemic hindlimbs resulted in a 2- to 3-fold increase in capillary density of neighboring host muscle by 1 week and out to 4 weeks with no evidence of hemangioma formation. Conclusions Local delivery of rVEGF from BAMs rapidly increases capillary density both within the BAM itself and in adjacent ischemic muscle tissue. Genetically engineered muscle tissue provides a method for therapeutic protein delivery in a dose-regulated fashion.
Warfarin-Related Nephropathy Modeled by Nephron Reduction and Excessive Anticoagulation
Authors: Kyle Ware, Polina Brodsky, Anjali A. Satoskar, Tibor Nadasdy, Gyongyi Nadasdy, Haifeng Wu, Brad H. Rovin, Udayan Bhatt, Jon Von Visger, Lee A. Hebert, Sergey V. Brodsky
Journal: Journal of the American Society of Nephrology (2011)

An acute increase in international normalized ratio (INR) to >3.0 in patients with chronic kidney disease (CKD) can associate with an unexplained acute increase in serum creatinine and accelerated progression of CKD. A subset of these patients have renal tubular obstruction by casts of red blood cells, presumably the dominant mechanism of the acute kidney injury described as warfarin-related nephropathy. Here, we developed an animal model of this acute kidney injury that is based on the 5/6-nephrectomy model to aid future investigation of the pathogenesis of this condition. We found that acute excessive anticoagulation with brodifacoum ("superwarfarin") increased serum creatinine levels and hematuria in 5/6-nephrectomized rats but not in controls. In addition, morphologic findings in 5/6-nephrectomized rats included glomerular hemorrhage, occlusive red blood cell casts, and acute tubular injury, similar to the biopsy findings among affected patients. Furthermore, in the rat model, we observed an increase in apoptosis of glomerular endothelial cells. In summary, the 5/6-nephrectomy model combined with excessive anticoagulation may be a useful tool to study the pathogenesis of warfarin-related nephropathy.
Descriptive epidemiology of vestibular schwannomas1
Authors: Jennifer M. Propp, Bridget J. McCarthy, Faith G. Davis, Susan Preston-Martin
Journal: Neuro-Oncology (2006)

Vestibular schwannomas, commonly termed acoustic neuromas, arise from the vestibular branch of the eighth cranial nerve (acoustic nerve) and are benign, slow-growing brain tumors that negatively impact patient quality of life. They are thought to account for the majority of intracranial nerve sheath tumors. To describe incidence rate patterns and trends of primary nerve sheath tumors of the brain/CNS and the subset of vestibular schwannomas in two population-based incidence registries, data were obtained from 11 Central Brain Tumor Registry of the United States (CBTRUS) collaborating state registries and the Los Angeles County Cancer Surveillance Program (LACCSP) (1975-1998). Average annual incidence rates were tabulated by age, gender, race, year, and region and were age-adjusted to the year 2000 U.S. standard population. Multiplicative Poisson regression models were used to compare trends in primary nerve sheath tumors of the brain/CNS overall and in subgroups, including vestibular schwannomas, controlling for age, gender, race, microscopic confirmation, and region. Joinpoint regression analysis was used to identify any sharp changes in incidence over time. The overall incidence of primary nerve sheath tumors of the brain/CNS was 1.1 per 100,000 person-years (CBTRUS, 1995-1999 and LACCSP, 1995-1998). The incidence of vestibular schwannomas was similar for both data sets: 0.6 per 100,000 person-years (CBTRUS, 1995-1999) and 0.8 per 100,000 person-years (LACCSP, 1995-1998). Moreover, the incidence of primary nerve sheath tumors of the brain/CNS overall (CBTRUS, 1985-1999 and LACCSP, 1975-1998) and of vestibular schwannomas (CBTRUS, 1992-1999 and LACCSP, 1992-1998) increased over time. However, the incidence of benign schwannomas in sites other than the acoustic nerve either decreased (CBTRUS, 1992-1999) or experienced no significant change (LACCSP, 1992-1998). While improvements in diagnosis and reporting may explain some of these trends, further consideration of potential etiologic factors may be warranted.
PSYCHOSES IN NAVAL OFFICERS: A PLEA FOR PSYCHIATRIC SELECTION
Authors: Z. M. LEBENSOHN
Journal: American Journal of Psychiatry (1945)

Great and deserved emphasis has been placed on the psychiatric selection of enlisted personnel but officer candidates of the Naval Reserve are still appointed without the benefit of any special psychiatric examination. Prospective officers are subjected to painstaking investigations and thorough physical examinations, and these procedures have been so effective that the incidence of psychoses in officers is far below that encountered among enlisted men. Despite this good record, a substantial number of officers with gross psychiatric defects in personality or background have been commissioned under the present method of officer selection. A study of a statistically valid series of such officers, who have developed psychoses requiring treatment at St. Elizabeths Hospital, reveals a surprisingly high number with histories of previous hospitalizations for mental illness, prolonged neuropsychiatric treatment or obvious emotional instability and inadequacy. It is believed that most of these could have been eliminated with even a minimal psychiatric investigation. The importance of psychiatric selection of naval officer personel can hardly be overemphasized when the possibilities for catastrophe, the grave damage to morale and great loss of time, training and money is considered.
A Prospective, Controlled Trial of a Protocol-based Strategy to Discontinue Mechanical Ventilation
Authors: Jerry A. Krishnan, Dana Moore, Carey Robeson, Cynthia S. Rand, Henry E. Fessler
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Weaning protocols can improve outcomes, but their efficacy may vary with patient and staff characteristics. In this prospective, controlled trial, we compared protocol-based weaning to usual, physician-directed weaning in a closed medical intensive care unit (ICU) with high physician staffing levels and structured, system-based rounds. Adult patients requiring mechanical ventilation for more than 24 hours were assigned to usual care (UC) or protocol weaning based on their hospital identification number. Patients assigned to UC (n=145) were managed at their physicians' discretion. Patients assigned to protocol (n=154) underwent daily screening and a spontaneous breathing trial by respiratory and nursing staff without physician intervention. There were no significant baseline differences in patient characteristics between groups. The proportion of patients (protocol vs. UC) who successfully discontinued mechanical ventilation (74.7% vs. 75.2%, p=0.92), duration of mechanical ventilation (median [interquartile range]: 60.4 hours [28.6-167.0 hours] vs. 68.0 hours [27.1-169.3 hours], p=0.61), ICU (25.3% vs. 28.3%) and hospital mortality (36.4% vs. 33.1%), ICU length of stay (115 vs. 146 hours), and rates of reinstituting mechanical ventilation (10.3% vs. 9.0%) was similar. We conclude that protocol-directed weaning may be unnecessary in a closed ICU with generous physician staffing and structured rounds.
Personality and Depression: Explanatory Models and Review of the Evidence
Authors: Daniel N. Klein, Roman Kotov, Sara J. Bufferd
Journal: Annual Review of Clinical Psychology (2011)

Understanding the association between personality and depression has implications for elucidating etiology and comorbidity, identifying at-risk individuals, and tailoring treatment. We discuss seven major models that have been proposed to explain the relation between personality and depression, and we review key methodological issues, including study design, the heterogeneity of mood disorders, and the assessment of personality. We then selectively review the extensive empirical literature on the role of personality traits in depression in adults and children. Current evidence suggests that depression is linked to traits such as neuroticism/negative emotionality, extraversion/positive emotionality, and conscientiousness. Moreover, personality characteristics appear to contribute to the onset and course of depression through a variety of pathways. Implications for prevention and prediction of treatment response are discussed, as well as specific considerations to guide future research on the relation between personality and depression.
Teenage Sex and Birth Control
Authors: E. James Lieberman
Journal: JAMA (1978)

AFTER nearly a decade of survey research, experts have found that adolescents are in the forefront, the middle, and the tail end of the sexual revolution. However, some young people have joined the resistance, hiding underground and defending virgin territory. Teenagers are diverse and changeable; nationwide studies by Zelnik and Kantner<sup>1</sup>of Johns Hopkins University provide the best perspective available on premarital sex and its risks. In 1976 they found that 40% of unmarried women between 15 and 19 years of age had experienced intercourse at least once. In the past few years, an increasing number of those sexually active used contraception some or all of the time, but the majority are still taking chances. Physicians may be asked an infinite variety of questions, many of which they will cope with easily. The following is my choice of current topics that could or should be discussed in a physician's
Rituximab-CHOP Versus CHOP Alone or With Maintenance Rituximab in Older Patients With Diffuse Large B-Cell Lymphoma
Authors: Thomas M. Habermann, Edie A. Weller, Vicki A. Morrison, Randy D. Gascoyne, Peter A. Cassileth, Jeffrey B. Cohn, Shaker R. Dakhil, Bruce Woda, Richard I. Fisher, Bruce A. Peterson, Sandra J. Horning
Journal: Journal of Clinical Oncology (2006)

Purpose To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients. Patients and Methods Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided. Results Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone. Conclusion Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.
P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are induced by arsenic trioxide (As2O3), but are not the main mechanism of As2O3-resistance in acute promyelocytic leukemia cells
Authors: A Takeshita, K Shinjo, K Naito, H Matsui, K Shigeno, S Nakamura, T Horii, M Maekawa, K Kitamura, T Naoe, K Ohnishi, R Ohno
Journal: Leukemia (2003)
Benzethonium Chloride: A Novel Anticancer Agent Identified by Using a Cell-Based Small-Molecule Screen
Authors: Kenneth W. Yip, Xinliang Mao, P.Y. Billie Au, David W. Hedley, Sue Chow, Shadi Dalili, Joseph D. Mocanu, Carlo Bastianutto, Aaron Schimmer, Fei-Fei Liu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: This study aims to identify a novel therapeutic agent for head and neck cancer and to evaluate its antitumor efficacy. Experimental Design: A cell-based and phenotype-driven high-throughput screening of ∼2,400 biologically active or clinically used compounds was done using a tetrazolium-based assay on FaDu (hypopharyngeal squamous cancer) and NIH 3T3 (untransformed mouse embryonic fibroblast) cells, with secondary screening done on C666-1 (nasopharyngeal cancer) and GM05757 (primary normal human fibroblast) lines. The “hit” compound was assayed for efficacy in combination with standard therapeutics on a panel of human cancer cell lines. Furthermore, its mode of action (using transmission electron microscopy and flow cytometry) and its in vivo efficacy (using xenograft models) were evaluated. Results: Benzethonium chloride was identified as a novel cancer-specific compound. For benzethonium (48-hour incubation), the dose required to reduce cell viability by 50% was 3.8 μmol/L in FaDu, 42.2 μmol/L in NIH 3T3, 5.3 μmol/L in C666-1, and 17.0 μmol/L in GM05757. In vitro, this compound did not interfere with the effects of cisplatin, 5-fluorouracil, or γ-irradiation. Benzethonium chloride induced apoptosis and activated caspases after 12 hours. Loss of mitochondrial membrane potential (ΔΨM) preceded cytosolic Ca2+ increase and cell death. In vivo, benzethonium chloride ablated the tumor-forming ability of FaDu cells, delayed the growth of xenograft tumors, and combined additively with local tumor radiation therapy. Evaluation of benzethonium chloride on the National Cancer Institute/NIH Developmental Therapeutics Program 60 human cancer cell lines revealed broad-range antitumor activity. Conclusions: This high-throughput screening identified a novel antimicrobial compound with significant broad-spectrum anticancer activity.
The value of “negative” appraisals for resilience. Is positive (re)appraisal always good and negative always bad?
Authors: Alexandra M. Freund, Ursula M. Staudinger
Journal: Behavioral and Brain Sciences (2015)

In contrast to the PASTOR model by Kalisch et al. we point to the potential negative long-term effects of positive (re)appraisals of events for resilience. This perspective posits that emotional reactions to events provide important guidelines as to which events, environments, or social relations should be sought out and which ones should be avoided in the future.
New Strategies in Hodgkin Lymphoma: Better Risk Profiling and Novel Treatments
Authors: Catherine Diefenbach, Christian Steidl
Journal: Clinical Cancer Research (2013)

Recent advances in Hodgkin lymphoma research are expected to prelude a promising new treatment era for patients and their treating physicians. Scientific investigations over the last few years have provided new insights into risk stratification, and, simultaneously, a plethora of novel targeted therapies are emerging for patients with relapsed and refractory disease. These novel therapies will be tested primarily in high-risk patients because 75% of the patients are cured with conventional therapies. The challenges, as Hodgkin lymphoma therapy moves forward, will be using these biologic insights to identify the patients who may benefit earlier in treatment from these novel agents, and tailoring the therapy to the tumor biology of the patient. These dual aims are intertwined; as our therapeutic arsenal increases, these biologic determinants of risk may themselves inform the design of therapies and the choice of treatments for high-risk patients.
DNA Methylation Modifies the Effect of Genotype on Atopy Risk
Authors: Gabrielle A. Lockett, Nelís Soto-Ramírez, Sanjay K. Lal, Susan L. Ewart, Hasan Arshad, Hongmei Zhang, Wilfried Karmaus, John W. Holloway
Journal: Journal of Allergy and Clinical Immunology (2015)
Hospice and Where the Doctor Can Be
Authors: Mark R. Litzow, Timothy J. Moynihan
Journal: Journal of Clinical Oncology (2013)

ticulately describes the challenging and conflicting emotions that hematologists and oncologists feel when they learn of the death of patients to whom they have become close while caring for them during their illness. He discusses the sense of abandoning their patients that physicians may experience when referring their patients for hospice care. We do not know the detailed circumstances of Geynisman’s patients that led to his inability to participate in their care when they entered hospice, but we do wish to remind our hematology and oncology colleagues that when they refer their patients for hospice care, they need not abandon them. Medicare does allow the hospice attending of record to bill Medicare part B for professional services that are provided to the patient. 2 These are not limited to care relating to the terminal illness and are billed separately from the fees that are paid to the hospice medical director. The hospice physicians and nurses provide a close supportive and consultative/advisory role. This allows patients and their families to maintain continuity of care and to know that the physician who walked with them through their challenging journey of malignant disease has not abandoned them. This includes the potential for continued office visits when appropriate, which can still be reimbursed at standard rates. Support from the hospice team often also allows the physician to manage the patient’s care from a distance, when travel back to the clinic would be an excessive burden for the patient and family, with the hospice team serving as the remote physician’s eyes and ears. Home visits, when practical, are greatly rewarding and remembered by the family long after the patient dies. Although challenging, it can also be immensely gratifying to support patients and families whom we have come to know so well during this most difficult time in their lives.
Putrescine as a source of instant energy in the small intestine of the rat
Authors: S Bardócz, G Grant, D S Brown, A Pusztai
Journal: Gut (1998)

Background and aims —It has been suggested that putrescine acts as a growth factor in the gut, but its exact function in some aspects of cellular metabolism is still in question. The aim of the present work was to identify some functions of putrescine in small bowel metabolism. Animals —Rats (about 80 g), in groups of five, were given either phytohaemagglutinin- or lactalbumin-containing diets, fed ad libitum or were fasted for 48 hours and re-fed for six or twelve hours before being killed. Methods —Uptake of intraperitoneally or intragastrically administered [ 14 C]putrescine and its conversion to succinate by the rat small bowel mucosa was measured. Tissue polyamine and succinate contents were measured by high performance liquid chromatography and amino acid analysis respectively. Results —Uptake of putrescine by the small bowel mucosa from the systemic circulation and conversion of about 30% of this to succinate occurs in the epithelium of the healthy small bowel. Compared with rats given food ad libitum, putrescine uptake was doubled in fasted animals and more than 70% of it was converted to succinate. All these changes returned to control values on refeeding. Using phyto- haemagglutinin induced gut growth as a model, the uptake of putrescine from the systemic circulation by the serosal side of the small intestinal epithelium was increased immediately after growth was stimulated. During phytohaemagglutinin induced growth of the gut, putrescine was converted to succinate in the same proportion as in the healthy small bowel. Conclusions —The experiments identified a novel function for putrescine in gut metabolism: it can be used as an instant energy source when required.
Brief intervention during hospital admission to help patients to give up smoking after myocardial infarction and bypass surgery: randomised controlled trial
Authors: P. Hajek, T. Z Taylor, P. Mills
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems. <b>Design:</b> Randomised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses. <b>Setting:</b> Inpatient wards in 17 hospitals in England. <b>Participants:</b> 540 smokers admitted to hospital after myocardial infarction or for cardiac bypass surgery who expressed interest in stopping smoking. <b>Intervention:</b> Brief verbal advice and standard booklet (usual care). Intervention lasting 20-30 minutes including carbon monoxide reading, special booklet, quiz, contact with other people giving up, declaration of commitment to give up, sticker in patient9s notes (intervention group). <b>Main outcome measures:</b> Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points. Feasibility of the intervention and delivery of its components. <b>Results:</b> After six weeks 151 (59%) and 159 (60%) patients remained abstinent in the control and intervention group, respectively (P=0.84). After 12 months the figures were 102 (41%) and 94 (37%) (P=0.40). Recruitment was slow, and delivery of the intervention was inconsistent, raising concerns about the feasibility of the intervention within routine care. Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it (P&lt;0.01). Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome. Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infarction. <b>Conclusions:</b> Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers. <h3>What is already known on this topic</h3> Stopping smoking after a serious cardiac event is associated with a significant decrease in mortality Up to 70% of smokers who survive cardiac surgery smoke again within a year Intensive interventions delivered by dedicated staff can help cardiac patients not to start to smoke again <h3>What this study adds</h3> An intervention delivered by cardiac rehabilitation nurses within routine care during patients9 hospital stay failed to increase the number who managed to stop smoking in the long term For busy staff with competing priorities, the 30 minute intervention was also on the borderline of practicability Patients admitted after a myocardial infarction were over twice as likely to give up than those admitted for a bypass operation