tbuckley/cabot-search huggingface dataset:
Improving Care for Depression and Suicide Risk in Adolescents: Innovative Strategies for Bringing Treatments to Community Settings
Authors: Joan Rosenbaum Asarnow, Jeanne Miranda
Journal: Annual Review of Clinical Psychology (2014)

This article reviews the literature on interventions and services for depression and suicide prevention among adolescents, with the goals of placing this science within the context of currently changing health care environments and highlighting innovative models for improving health and mental health. We examine the challenges and opportunities offered by new initiatives and legislation designed to transform the US health and mental health care systems; summarize knowledge regarding the treatment of depression and suicidality/self-harm in adolescents; and describe innovative models for partnering with health systems and communities. This review demonstrates that treatment models and service delivery strategies are currently available for increasing evidence-based care, particularly for depression, and concludes with recommendations for future research and quality improvement initiatives aimed at inspiring additional efforts to put science to work, bridge science and community practice, and develop strategies for partnering with communities to improve care, mental health, and well-being among adolescents.
Age-related cardiovascular effects of catecholamines in anesthetized piglets.
Authors: N M Buckley, P M Gootman, E L Yellin, P Brazeau
Journal: Circulation Research (1979)

We studied cardiac and peripheral circulatory effects of graded doses of catecholamines (0.05-1.0 microgram/kg) in piglets aged less than or equal to 1 day, 2--4 days, 1 wweek, 2 weeks, and 2.5-3 months, under anesthesia with pentobarbital. We evaluated cardiovascular function from simultaneous recordings of aortic pressure, ventricular pressure and its first derivative, heart rate, and phasic carotid and femoral blood flows. We calculated vascular resistance as the ratio of mean aortic pressure to mean flow. The age of onset of a given cardiovascular response was determined, and magnitudes of each type of response were compared among the age groups. Norepinephrine elevated the blood pressure at all doses in piglets of all ages, elicited reflex bradycardia only in older piglets, and increased carotid resistance. Epinephrine elevated the blood pressure at all doses in piglets less than 1 week old, but low doses lowered the blood pressure in piglets older than 1 week of age; resistance changes in the femoral and carotid circulations were variable except in the 2.5-3 month age group. Isoproterenol increased cardiac contractility at all doses in piglets of all ages and increased heart rate at low doses in piglets older than 2 days of age; however, blood pressure and femoral resistance decreases were age and dose dependent. There were age-related differences in the catecholamine dose required to elicit a given cardiac or peripheral circulatory effect and age-related differences in the direction and magnitude of such effects. These results provide evidence for differing rates of postnatal maturation of cardiovascular alpha- and beta- adrenergic mechanisms in swine.
Blood culture bottle culture of pleural fluid in pleural infection
Authors: S. M. Menzies, N. M. Rahman, J. M. Wrightson, H. E. Davies, R. Shorten, S. H. Gillespie, C. W. H. Davies, N. A. Maskell, A. A. Jeffrey, Y. C. G. Lee, R. J. O. Davies
Journal: Thorax (2011)

Background Pleural infection is common, and has a >30% major morbidity and mortality—particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform. Objectives To determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce. Methods 62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for ‘false-positive’ results. Results The addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference −2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative. Conclusions Blood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.
Idiotype-antiidiotype regulation. IV. Expression of common regulatory idiotopes on fructosan-binding and non-fructosan-binding monoclonal immunoglobulin.
Authors: B Goldberg, W E Paul, C A Bona
Journal: The Journal of Experimental Medicine (1983)

The ABPC-48 Id (A48 Id) is normally not expressed in detectable amounts in the serum of BALB/c mice that have been immunized with bacterial levan (BL). However, A48 Id-bearing anti-BL clones can be activated in BL-immunized mice by three distinct prior treatments: (a) administration of A48 Id-bearing monoclonal proteins to newborn mice; (b) administration of minute amounts of anti-Id antibodies to newborn mice; and (c) production of anti-(anti-A48 Id) antibodies (Ab3), in adult mice. From these three groups of mice, eighteen monoclonal antibodies (MAb) expressing A48 Id were obtained. Regarding the binding specificity, these MAb can be divided into three groups: one that binds only BL, the second that binds BL and displays low cross-reactivity for inulin, and the third that lacks BL- and inulin-binding activity. This latter group was obtained only from adult mice immunized with anti-A48 Id-KLH conjugate. Immuno-chemical analysis of these MAb has shown that the A48 Id is made up of several idiotopes, some of them associated with the combining site and others nonantigen inhibitable. Comparisons of the amino acid sequence of the UPC-10 and A48 VH regions, and the distribution of the A48 Id family on A48, UPC-10, and three MAb, suggested that A48 regulatory idiotypes can be located on the framework segment of VH region. Furthermore, we screened 198 mouse and 80 human myeloma proteins for their ability to express A48 Id. Of these, only MOPC-167, an IgAk phosphocholine (PC)-binding myeloma protein, gave a significant inhibition of binding of labeled A48 to anti-A48 Id antibodies by radioimmunoassay and enzyme-linked immunosorbent assay. In addition, the binding of labeled MOPC-167 to anti-A48 Id antibodies was not inhibited by PC but was inhibited by A48 and 3-76-42 MAb bearing A48, UPC-10 non-antigen-inhibitable idiotopes. These results extend our prediction that the regulatory idiotopes can be expressed not only on antibodies specific for a family of antigens or members of the same network pathway, but also can be shared by antibodies with different antigenic specificity.
Nicotine replacement therapy in smoking cessation
Authors: I Campbell
Journal: Thorax (2003)

Evidence for benefit from nicotine replacement therapy in hospital patients is inconclusive, although the results of a trial reported in this issue of Thorax give cause for optimism and should stimulate further studies.

Most smokers become nicotine dependent and, when they stop smoking, experience withdrawal symptoms and craving. Nicotine replacement therapy (NRT) reduces these unpleasant symptoms and, theoretically, should decrease the risk of relapse. Smoking cessation is properly defined as validated sustained abstinence from cigarettes and/or other tobacco products for at least 6 months, but preferably for 1 year. This editorial includes evidence only from those studies which have applied such a definition and which have specified their settings and populations.

NRT is available as chewing gum, transdermal patches, sublingual tablets, lozenges, inhalation cartridges and nasal spray. In specialised cessation clinics1–8 and in primary care,9,10 prospective randomised clinical trials have shown that NRT, used as an adjunct to advice and support, results in better cessation rates than does advice and support alone. In the clinics success rates with NRT tend to be higher (11–30%) and more consistent than in primary care, where some studies have found no significant difference from placebo.11–14 One study in primary care showed 8% success with nicotine chewing gum compared with 4% with advice plus leaflet, but there was no placebo controlled arm.15 Two studies of transdermal nicotine in primary care have shown success rates of around 10%, which were superior to those with placebo (around 6%).9,10 The benefit for transdermal nicotine in cessation clinics6–8 and in primary care9,10 is thus clear, whereas nicotine chewing gum,1–5 inhaler,16,17 …
Circulating Serum Free Light Chains As Predictive Markers of AIDS-Related Lymphoma
Authors: Ola Landgren, James J. Goedert, Charles S. Rabkin, Wyndham H. Wilson, Kieron Dunleavy, Robert A. Kyle, Jerry A. Katzmann, S. Vincent Rajkumar, Eric A. Engels
Journal: Journal of Clinical Oncology (2010)

PURPOSE HIV-infected persons have an elevated risk of developing non-Hodgkin's lymphoma (NHL); this risk remains increased in the era of effective HIV therapy. We evaluated serum immunoglobulin (Ig) proteins as predictors of NHL risk among HIV-infected individuals. PATIENTS AND METHODS By using three cohorts of HIV-infected persons (from 1982 to 2005), we identified 66 individuals who developed NHL and 225 matched (by cohort, sex, ethnicity, age, and CD4 count), HIV-infected, lymphoma-free controls who had available stored prediagnostic blood samples. Serum/plasma samples obtained 0 to 2 years and 2 to 5 years before diagnosis/selection were assayed for IgG, IgM, and IgA levels; monoclonal (M) Igs; and kappa and lambda free light chain (FLC) levels. Patients and matched controls were compared by using conditional logistic regression. Results The kappa and lambda FLCs were both significantly higher in patients (eg, in 2- to 5-year window: median kappa, 4.24 v 3.43 mg/dL; median lambda, 4.04 v 3.09 mg/dL) and strongly predicted NHL in a dose-response manner up to 2 to 5 years before diagnosis/selection (eg, NHL risk 3.76-fold higher with kappa concentration at least 2.00 times the upper limit of normal, and 8.13-fold higher with lambda concentration at least 2.00 times the upper limit of normal compared with normal levels). In contrast, IgG, IgM, and IgA levels were similar in patients and controls. M proteins were detected in only two patients with NHL (3%) and in nine controls (4%), and they were not significantly associated with NHL risk. CONCLUSION Elevated FLCs may represent sensitive markers of polyclonal B-cell activation and dysfunction and could be useful for identifying HIV-infected persons at increased NHL risk.
One in seven foundation trusts failed to submit data on complaints
Authors: A. O'Dowd
Journal: BMJ (2010)

NHS foundation trusts should be forced to submit data on patients’ complaints to the NHS Information Centre, as other trusts have to do, critics have said.

The call is in response to data published on 25 August by the NHS Information Centre showing that 18 of the 130 foundation trusts did not submit any information on patients’ written complaints because, unlike for traditional NHS trusts, it is not mandatory for them to do so.

The centre’s new figures show that from 2008-9 to 2009-10 the number of complaints in the NHS rose from 89 139 to 101 077, a 13.4% rise and the biggest since the annual data were first published 12 years ago.

Katherine Murphy, …
Molecular Imaging Reveals a Role for AKT in Resistance to Cisplatin for Ovarian Endometrioid Adenocarcinoma
Authors: Hanxiao Wang, Stefanie Galbán, Rong Wu, Brittany M. Bowman, Amanda Witte, Katrin Vetter, Craig J. Galbán, Brian D. Ross, Kathleen R. Cho, Alnawaz Rehemtulla
Journal: Clinical Cancer Research (2012)

Ovarian cancer is the fifth leading cause of cancer-related deaths among American women. Platinum-based chemotherapy, such as cisplatin, represents the standard-of-care for ovarian cancer. However, toxicity and acquired resistance to cisplatin have proven challenging in the treatment of patients with ovarian cancer.Using a genetically engineered mouse model of ovarian endometrioid adenocarcinoma (OEA) in combination with molecular-imaging technologies, we studied the activation of the AKT serine/threonine kinase in response to long-term cisplatin therapy.Treatment of cells in culture and tumor-bearing animals with cisplatin resulted in activation of AKT, a key mediator of cell survival. On the basis of these results, we investigated the therapeutic use of AKT inhibition in combination with cisplatin, which resulted in enhanced and prolonged induction of apoptosis and in significantly improved tumor control as compared with either agent alone.These results provide an impetus for clinical trials using combination therapy. To facilitate these trials, we also show the use of diffusion-weighted MRI as an imaging biomarker for evaluation of therapeutic efficacy in OEA.
CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo
Authors: Nicole Mende, Erika E. Kuchen, Mathias Lesche, Tatyana Grinenko, Konstantinos D. Kokkaliaris, Helmut Hanenberg, Dirk Lindemann, Andreas Dahl, Alexander Platz, Thomas Höfer, Federico Calegari, Claudia Waskow
Journal: The Journal of Experimental Medicine (2015)

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1–CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1–CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1–CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis.
Interplay between FGF21 and insulin action in the liver regulates metabolism
Authors: Brice Emanuelli, Sara G. Vienberg, Graham Smyth, Christine Cheng, Kristin I. Stanford, Manimozhiyan Arumugam, Mervyn D. Michael, Andrew C. Adams, Alexei Kharitonenkov, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2014)

The hormone FGF21 regulates carbohydrate and lipid homeostasis as well as body weight, and increasing FGF21 improves metabolic abnormalities associated with obesity and diabetes. FGF21 is thought to act on its target tissues, including liver and adipose tissue, to improve insulin sensitivity and reduce adiposity. Here, we used mice with selective hepatic inactivation of the IR (LIRKO) to determine whether insulin sensitization in liver mediates FGF21 metabolic actions. Remarkably, hyperglycemia was completely normalized following FGF21 treatment in LIRKO mice, even though FGF21 did not reduce gluconeogenesis in these animals. Improvements in blood sugar were due in part to increased glucose uptake in brown fat, browning of white fat, and overall increased energy expenditure. These effects were preserved even after removal of the main interscapular brown fat pad. In contrast to its retained effects on reducing glucose levels, the effects of FGF21 on reducing circulating cholesterol and hepatic triglycerides and regulating the expression of key genes involved in cholesterol and lipid metabolism in liver were disrupted in LIRKO mice. Thus, FGF21 corrects hyperglycemia in diabetic mice independently of insulin action in the liver by increasing energy metabolism via activation of brown fat and browning of white fat, but intact liver insulin action is required for FGF21 to control hepatic lipid metabolism.
Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis
Authors: Fan Fan, Chen Ji, Yumei Wu, Shawn M. Ferguson, Natalia Tamarina, Louis H. Philipson, Xuelin Lou
Journal: Journal of Clinical Investigation (2015)

Alterations in insulin granule exocytosis and endocytosis are paramount to pancreatic β cell dysfunction in diabetes mellitus. Here, using temporally controlled gene ablation specifically in β cells in mice, we identified an essential role of dynamin 2 GTPase in preserving normal biphasic insulin secretion and blood glucose homeostasis. Dynamin 2 deletion in β cells caused glucose intolerance and substantial reduction of the second phase of glucose-stimulated insulin secretion (GSIS); however, mutant β cells still maintained abundant insulin granules, with no signs of cell surface expansion. Compared with control β cells, real-time capacitance measurements demonstrated that exocytosis-endocytosis coupling was less efficient but not abolished; clathrin-mediated endocytosis (CME) was severely impaired at the step of membrane fission, which resulted in accumulation of clathrin-coated endocytic intermediates on the plasma membrane. Moreover, dynamin 2 ablation in β cells led to striking reorganization and enhancement of actin filaments, and insulin granule recruitment and mobilization were impaired at the later stage of GSIS. Together, our results demonstrate that dynamin 2 regulates insulin secretory capacity and dynamics in vivo through a mechanism depending on CME and F-actin remodeling. Moreover, this study indicates a potential pathophysiological link between endocytosis and diabetes mellitus.
A phase I/II trial of enzastaurin in patients with recurrent high-grade gliomas
Authors: Teri N. Kreisl, Svetlana Kotliarova, John A. Butman, Paul S. Albert, Lyndon Kim, Luna Musib, Donald Thornton, Howard A. Fine
Journal: Neuro-Oncology (2010)

Enzastaurin, a potent inhibitor of protein kinase C-beta, inhibits angiogenesis and has direct cytotoxic activity against glioma cells in preclinical studies. Patients with recurrent high-grade gliomas were stratified by histology and use of enzyme-inducing antiepileptic drugs (EIAEDs). Patients on EIAED were treated on the phase I dose-escalation portion of the trial with evaluation of serum pharmacokinetics as the primary endpoint. Patients not on EIAED were treated on the phase II portion of the trial with radiographic response and progression-free survival (PFS) as primary objectives. Patients in phase I received enzastaurin 525–900 mg/d. Phase II patients received 500 or 525 mg/d. One hundred and eighteen patients were accrued to this trial. Therapy was well tolerated with thrombosis, thrombocytopenia, hemorrhage, and elevated alanine aminotransferase as the most commonly observed drug-associated grade 3 or higher toxicities. Patients on EIAED had serum enzastaurin exposure levels approximately 80% lower than those not on EIAED. Dose escalations up to 900 mg/d did not substantially increase serum exposure levels and a maximally tolerated dose was never reached. Twenty-one of 84 evaluable patients (25%) experienced an objective radiographic response. The 6-month PFS was 7% for patients with glioblastoma and 16% for patients with anaplastic glioma. Phosphorylation of glycogen synthase kinase-3 in peripheral blood mononuclear cells was identified as a potential biomarker of drug activity. Enzastaurin has anti-glioma activity in patients with recurrent high-grade glioma, but does not appear to have enough single-agent activity to be useful as monotherapy.
Cause-Specific Mortality in Long-Term Survivors of Retinoblastoma
Authors: C.-L. Yu, M. A. Tucker, D. H. Abramson, K. Furukawa, J. M. Seddon, M. Stovall, J. F. Fraumeni, R. A. Kleinerman
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundSubsequent malignant neoplasms are a major cause of premature death in survivors of hereditary retinoblastoma. Radiotherapy further increases the risk of death. Mortality information is limited among long-term survivors who were irradiated for hereditary retinoblastoma.
Imagery Rehearsal Therapy for Chronic Nightmares in Sexual Assault Survivors With Posttraumatic Stress Disorder
Authors: Barry Krakow, Michael Hollifield, Lisa Johnston, Mary Koss, Ron Schrader, Teddy D. Warner, Dan Tandberg, John Lauriello, Leslie McBride, Lisa Cutchen, Diana Cheng, Shawn Emmons, Anne Germain, Dominic Melendrez, Diane Sandoval, Holly Prince
Journal: JAMA (2001)

ContextChronic nightmares occur frequently in patients with posttraumatic stress disorder (PTSD) but are not usually a primary target of treatment.ObjectiveTo determine if treating chronic nightmares with imagery rehearsal therapy (IRT) reduces the frequency of disturbing dreams, improves sleep quality, and decreases PTSD symptom severity.Design, Setting, and ParticipantsRandomized controlled trial conducted from 1995 to 1999 among 168 women in New Mexico; 95% had moderate-to-severe PTSD, 97% had experienced rape or other sexual assault, 77% reported life-threatening sexual assault, and 58% reported repeated exposure to sexual abuse in childhood or adolescence.InterventionParticipants were randomized to receive treatment (n = 88) or to the wait-list control group (n = 80). The treatment group received IRT in 3 sessions; controls received no additional intervention, but continued any ongoing treatment.Main Outcome MeasuresScores on the Nightmare Frequency Questionnaire (NFQ), Pittsburgh Sleep Quality Index (PSQI), PTSD Symptom Scale (PSS), and Clinician-Administered PTSD Scale (CAPS) at 3- and 6-month follow-up.ResultsA total of 114 participants completed follow-up at 3 and/or 6 months. Comparing baseline to follow-up (n = 97-114), treatment significantly reduced nights per week with nightmares (Cohen d = 1.24; P&lt;.001) and number of nightmares per week (Cohen d = 0.85; P&lt;.001) on the NFQ and improved sleep (on the PSQI, Cohen d = 0.67; P&lt;.001) and PTSD symptoms (on the PSS, Cohen d = 1.00; P&lt;.001 and on the CAPS, Cohen d = 1.53; P&lt;.001). Control participants showed small, nonsignificant improvements for the same measures (mean Cohen d = 0.21). In a 3-point analysis (n = 66-77), improvements occurred in the treatment group at 3-month follow-up (treatment vs control group, Cohen d = 1.15 vs 0.07 for nights per week with nightmares; 0.95 vs −0.06 for nightmares per week; 0.77 vs 0.31 on the PSQI, and 1.06 vs 0.31 on the PSS) and were sustained without further intervention or contact between 3 and 6 months. An intent-to-treat analysis (n = 168) confirmed significant differences between treatment and control groups for nightmares, sleep, and PTSD (all P&lt;.02) with moderate effect sizes for treatment (mean Cohen d = 0.60) and small effect sizes for controls (mean Cohen d = 0.14). Posttraumatic stress symptoms decreased by at least 1 level of clinical severity in 65% of the treatment group compared with symptoms worsening or not changing in 69% of controls (χ21 = 12.80; P&lt;.001).ConclusionsImagery rehearsal therapy is a brief, well-tolerated treatment that appears to decrease chronic nightmares, improve sleep quality, and decrease PTSD symptom severity.