tbuckley/cabot-search huggingface dataset:
Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis
Authors: Anthony Delitto, Sara R. Piva, Charity G. Moore, Julie M. Fritz, Stephen R. Wisniewski, Deborah A. Josbeno, Mark Fye, William C. Welch
Journal: Annals of Internal Medicine (2015)

Primary care management decisions for patients with symptomatic lumbar spinal stenosis (LSS) are challenging, and nonsurgical guidance is limited by lack of evidence.To compare surgical decompression with physical therapy (PT) for LSS and evaluate sex differences.Multisite randomized, controlled trial. (ClinicalTrials.gov: NCT00022776).Neurologic and orthopedic surgery departments and PT clinics.Surgical candidates with LSS aged 50 years or older who consented to surgery.Surgical decompression or PT.Primary outcome was physical function score on the Short Form-36 Health Survey at 2 years assessed by masked testers.The study took place from November 2000 to September 2007. A total of 169 participants were randomly assigned and stratified by surgeon and sex (87 to surgery and 82 to PT), with 24-month follow-up completed by 74 and 73 participants in the surgery and PT groups, respectively. Mean improvement in physical function for the surgery and PT groups was 22.4 (95% CI, 16.9 to 27.9) and 19.2 (CI, 13.6 to 24.8), respectively. Intention-to-treat analyses revealed no difference between groups (24-month difference, 0.9 [CI, -7.9 to 9.6]). Sensitivity analyses using causal-effects methods to account for the high proportion of crossovers from PT to surgery (57%) showed no significant differences in physical function between groups.Without a control group, it is not possible to judge success attributable to either intervention.Surgical decompression yielded similar effects to a PT regimen among patients with LSS who were surgical candidates. Patients and health care providers should engage in shared decision-making conversations that include full disclosure of evidence involving surgical and nonsurgical treatments for LSS.National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone
Authors: Jagan R. Muppidi, Tal I. Arnon, Yelena Bronevetsky, Natacha Veerapen, Masato Tanaka, Gurdyal S. Besra, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2011)

Specialized B cells residing in the splenic marginal zone (MZ) continuously survey the blood for antigens and are important for immunity to systemic infections. However, the cues that uniquely attract cells to the MZ have not been defined. Previous work demonstrated that mice deficient in cannabinoid receptor 2 (CB2) have decreased numbers of MZ B cells but it has been unclear whether CB2 regulates MZ B cell development or positioning. We show that MZ B cells are highly responsive to the CB2 ligand 2-arachidonylglycerol (2-AG) and that CB2 antagonism rapidly displaces small numbers of MZ B cells to the blood. Antagonism for longer durations depletes MZ B cells from the spleen. In mice deficient in sphingosine-1-phosphate receptor function, CB2 antagonism causes MZ B cell displacement into follicles. Moreover, CB2 overexpression is sufficient to position B cells to the splenic MZ. These findings establish a role for CB2 in guiding B cells to the MZ and in preventing their loss to the blood. As a consequence of their MZ B cell deficiency, CB2-deficient mice have reduced numbers of CD1d-high B cells. We show that CB2 deficiency results in diminished humoral responses to a CD1d-restricted systemic antigen.
Increased teniposide clearance with concomitant anticonvulsant therapy.
Authors: D K Baker, M V Relling, C H Pui, M L Christensen, W E Evans, J H Rodman
Journal: Journal of Clinical Oncology (1992)

A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients.The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data.The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P less than .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients.These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.
Electronic Cigarettes in North America
Authors: Caroline Franck, Talia Budlovsky, Sarah B. Windle, Kristian B. Filion, Mark J. Eisenberg
Journal: Circulation (2014)

Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns.We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking.Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation.
THE ROLE OF NON-PRECIPITATING ANTIBODIES IN THE PASSIVE SENSITIZATION OF HUMAN SKIN BY RABBIT ANTI-OVALBUMIN
Authors: William B. Sherman, Arthur E. O. Menzel, Paul M. Seebohm
Journal: The Journal of Experimental Medicine (1950)

Sera of fourteen rabbits injected with alum-precipitated recrystallized ovaltumin, containing 0.046 to 0.604 mg. of precipitable antibody nitrogen per ml. (average 0.299 mg.), passively sensitized human skin, while the sera of nine rabbits injected with dissolved recrystallized ovalbumin, containing from less than 0.05 to 0.420 of antibody nitrogen per ml. (average 0.176 mg. or less), were inactive in human skin. The skin-sensitizing activity of the sera bore no relation to the precipitin content. Removal of 68 to 90 per cent of the precipitin nitrogen by a single addition of antigen did not affect the activity of the sera in sensitizing human skin. Removal of all precipitable antibody nitrogen in one serum by a single addition of antigen removed the skin-sensitizing activity. The "univalent" antibody remaining after complete removal of precipitin by fractional addition of antigen showed the same activity in passive sensitization of human skin as the original serum.
A Prospective Study of Plasma C-Peptide and Colorectal Cancer Risk in Men
Authors: J. Ma, E. Giovannucci, M. Pollak, A. Leavitt, Y. Tao, J. M. Gaziano, M. J. Stampfer
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer. Methods: We conducted a nested case–control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age- and smoking status–matched control subjects. Information on four other insulin resistance–related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided. Results: Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance–related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide = 2.7, 95% confidence interval [CI] = 1.2 to 6.2; Ptrend = .047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile = 3.4, 95% CI = 1.4 to 8.3; Ptrend = .02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile = 3.4, 95% CI = 1.3 to 8.8; Ptrend = .03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was no apparent modification of risk by BMI, insulin resistance–related factors, or vigorous exercise. Conclusion: Elevated insulin production, as reflected by elevated concentrations of plasma C-peptide, may predict the risk of developing colorectal cancer, independently of BMI, factors related to insulin resistance, or levels of IGF-I and IGFBP-3.
Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer
Authors: Rebekah L Zinn, Eric E Gardner, Irina Dobromilskaya, Sara Murphy, Luigi Marchionni, Christine L Hann, Charles M Rudin
Journal: Molecular Cancer (2013)

Abstract Background New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies. Methods We explored the combination of ABT-737 and chloroquine, an inhibitor of autophagy, in preclinical models of SCLC. These included cell culture analyses of viability and of autophagic and apoptotic pathway induction, as well as in vivo analyses of efficacy in multiple xenograft models. Results Combination treatment of SCLC lines with ABT-737 and chloroquine decreased viability and increased caspase-3 activation over treatment with either single agent. ABT-737 induced several hallmarks of autophagy. However, knockdown of beclin-1, a key regulator of entry into autophagy, diminished the efficacy of ABT-737, suggesting either that the effects of chloroquine were nonspecific or that induction but not completion of autophagy is necessary for the combined effect of ABT-737 and chloroquine. ABT-737 and chloroquine in SCLC cell lines downregulated Mcl-1 and upregulated NOXA, both of which may promote apoptosis. Treatment of tumor-bearing mice demonstrated that chloroquine could enhance ABT-737-mediated tumor growth inhibition against NCI-H209 xenografts, but did not alter ABT-737 response in three primary patient-derived xenograft models. Conclusion These data suggest that although ABT-737 can induce autophagy in SCLC, autophagic inhibition by choroquine does not markedly alter in vivo response to ABT-737 in relevant preclinical models, arguing against this as a treatment strategy for SCLC.
Cystic pulmonary lesion in a 6 year old girl
Authors: B Niggemann, K Magdorf, J Waldschmidt, A Grassot, U Wahn
Journal: European Respiratory Journal (1994)

Case reportA 6 year old German girl, with no history of any chronic disease, fell ill with cough and otitis.Penicillin treatment was started.Because of fever, abdominal pain and worsening of the coughing during the next days, a chest X-ray was performed.It showed an extensive infiltration of the right upper lobe.Under suspicion of pneumonia, oral antibiotic treatment was extended to amoxycillin for 10 days.Meanwhile, fever had decreased.However, chest X-ray showed no improvement.The girl was referred to our department for further diagnostic procedures.Chest radiograph on admission (fig. 1) showed an infiltration of the right upper lobe, in which a fluid containing structure, with a round air bubble, attracted attention.In addition a dystelectasis of the middle lobe was noted.Because of these findings, the history and the subfebrile temperature of 38.5°C, an intravenous broad antibiotic treatment with fosfocine, gentamicin and metronidazole was started, under suspicion of an insufficiently treated pneumonia with liquefactive necrosis.Laboratory data revealed an elevated erythrocyte sedimentation rate of 60/120 mm, C-reactive protein was 1.3 mg•l -1 .Differential blood cell count was normal.Other data were also unremarkable: immunoglobulins, tumour markers alpha-fetoprotein (aFP) and human chorionic gonadotrophin (HCG), serological investigations concerning echinococcus and other pathogens.Intradermal tuberculin test with 10 tuberculin units (TU) purified protein derivative (PPD) remained negative.For further diagnosis bronchoscopy was performed, which showed thick, purulent hypersecretion from the right upper lobe.The cystic lesion could not be reached by any instrument.Bacteriological investigations remained without growth of any micro-organism.Taking all findings into consideration, an unresolved abscess forming pneumonia seemed to be the most probable diagnosis, at that time, and thoracic surgical intervention was performed.
The Burned Child: A Neglected Area of Psychiatry
Authors: ROSLYN SELIGMAN, BRUCE G. MACMILLAN, SHIRLEY S. CARROLL
Journal: American Journal of Psychiatry (1971)

Children suffering major burn injury were studied; four case vignettes are presented. Significant factors that emerged included unconscious motivation and early parent loss in some parents of burned children, an unexpected finding. Positive factors for survival were coping mechanisms of denial, withdrawal, splitting of the ego, somatic responses (hypertension, ulcers, and "seizures"), and hope in parents and/or staff. Follow-up revealed better adjustment than anticipated. The authors urge psychiatric involvement in the burned child and offer possible explanations of past neglect.
Are Psychiatrists Cost-Effective? An Analysis of Integrated Versus Split Treatment
Authors: M Dewan
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Managed care organizations prefer putatively less expensive split treatment, i.e., a psychopharmacologist plus a non-M.D. psychotherapist. In this study the cost of integrated care by a psychiatrist was compared with split care. METHOD: Using 1998 fee schedules of seven large managed care organizations (with 54.3% market share and 67.8 million lives) plus Medicare (37 million people), the author modeled clinical scenarios of psychotherapy alone, medication alone, and combined treatment provided by a psychiatrist or split with a psychologist or social worker. RESULTS: Brief psychotherapy by a social worker was the least expensive treatment. When treatment required both psychotherapy and medication, combined treatment by a psychiatrist cost about the same or less than split treatment with a social worker psychotherapist; it was usually less expensive than split treatment with a psychologist psychotherapist. CONCLUSIONS: The integrated biopsychosocial model practiced by psychiatry is both theoretically and economically the preferred model when combined treatment is needed.
Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation
Authors: PV Romero, U Lucangelo, J Lopez Aguilar, R Fernandez, L Blanch
Journal: European Respiratory Journal (1997)

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.
CITN11-02 interim trial results: subcutaneous administration of recombinant human IL-15 (rhIL-15) is associated with expansion of peripheral blood CD56+ NK cells and CD8+ T cells
Authors: Chihiro Morishima, Douglas G McNeel, Manish R Patel, Holbrook E Kohrt, Thomas A Waldmann, John A Thompson, Kevin C Conlon, Paul M Sondel, Heather A Wakelee, Minjun C Apodaca, Steven P Fling, Mary L Disis, Stephen P Creekmore, Jeffrey S Miller
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The Cancer Immunotherapy Trials Network is conducting a Phase I, dose-escalation study of subcutaneous (SQ) rhIL-15 in advanced melanoma, renal cell, non-small cell lung (NSCLC) and squamous cell head and neck carcinoma patients. IL-15 has been identified as a high priority agent
Critical Periods of Suicide Risk in Huntington’s Disease
Authors: Jane S Paulsen, Karin Ferneyhough Hoth, Carissa Nehl, Laura Stierman
Journal: American Journal of Psychiatry (2005)

Contrary to popular belief, receiving a diagnosis of a devastating fatal disease does not exacerbate, and may even alleviate, the risk of suicide. Suicidal ideation was examined in 4,171 individuals in the Huntington Study Group database. Participants were grouped according to a standardized neurological examination from 0 (i.e., normal examination) to 3 (definite Huntington’s disease). Patients with an unequivocal diagnosis of Huntington’s disease were further divided by stage of disease, from stage 1 (early) to stage 5 (end stage). Findings showed that the frequency of suicidal ideation doubled from 9.1% in at-risk persons with a normal neurological examination to 19.8% in at-risk persons with soft neurological signs and increased to 23.5% in persons with “possible Huntington’s disease.” In persons with a diagnosis of Huntington’s disease, 16.7% had suicidal ideation in stage 1, and 21.6% had suicidal ideation in stage 2, whereas the proportion of Huntington’s disease patients with suicidal ideation diminished thereafter. Findings suggest two critical periods for increased risk of suicide in Huntington’s disease. The first critical period is immediately before receiving a formal diagnosis of Huntington’s disease, and the second is in stage 2 of the disease, when independence diminishes. Although the underlying mechanisms of suicidal ideation in Huntington’s disease are poorly understood, it is critical for health care providers to be aware of periods during which patients may be at an increased risk.
Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis
Authors: J Ashitani, H Mukae, M Nakazato, T Ihi, H Mashimoto, J Kadota, S Kohno, S Matsukura
Journal: European Respiratory Journal (1998)

Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins. Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults. The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects. DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls. In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8. Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.