tbuckley/cabot-search huggingface dataset:
Abstract 20556: Safety and Efficacy of Intracoronary Hypoxia-PrecondItioned Bone Marrow Mononuclear Cells Administration for Acute Myocardial Infarction Patients
Authors: Xin Yang Hu, Xin Huang, Qian Yang, Lihan Wang, Jianzhong Sun, Hongwei Zhan, Jianjing Lin, Zhaoxia Pu, Jun Jiang, Yong Sun, Xianbao Liu, Xialjie Xie, Xia Yu, Zexin Chen, Hung-Fat Tse
Journal: Circulation (2014)

IMPORTANCE: Cell therapy has been a potential approach for ST-segment elevation acute myocardial infarction (STEMI). To improve the therapeutic oucome, the safety and efficacy of hypoxia-preconditioned (H-) bone marrow mononuclear cells (BMCs) in AMI patients need further evaluation. OBJECTIVE: To investigate the safety and efficacy of H-BMCs therapy in AMI patients. DESIGN: A phase 1, randomized and blinded study (February, 2011~ March, 2012) with one-year of follow-up. SETTING: A single center for hospitalized care. PARTICIPANTS: 22 Patients with an acute ST elevation myocardial infarction were recruited and randomized to two groups: normoxia BMCs (N-, n=11) and H-BMCs (n=11). INTERVENTIONS: Intracoronary infusion of H-BMCs or N-BMCs within 5-7 days after treatment with percutaneous transluminal coronary intervention (PCI). Patients were similarly treated by a stop-flow technique through an over-the-wire balloon catheter. MAIN OUTCOMES AND MEASURES: Primary endpoint was Treatment-emergent 30-day serious adverse event rate defined as a composite of death, MI, sustained ventricular tachycardia, stroke, hospitalization for worsening heart failure and revascularization. Secondary endpoints were change of myocardium perfusion, global left ventricular ejection fraction and left ventricular volumes. RESULTS: The primary endpoint events was none for N-BMCs and 9.1% (95% CI, 0.2%-41.3%) for H-BMCs. There was significant increase in the change of LVEF of H-BMCs group at 6 month. The change of end diastolic volume (EDV) and end systolic volume (ESV) in H-BMCs at 12 month were significantly decreased. Ratio of myocardium perfusion defect by Single-Photon Emission Computed Tomography (SPECT) was significantly reduced in H-BMCs group at 6 months, and score of myocardium perfusion defect by SPECT was significantly reduced than that of baseline in H-BMCs group at 6 and 12 months, unlike N- group. CONCLUSIONS AND RELEVANCE: Intracoronary infusion with H-BMCs appeared to be safe and effective for patients with AMI. Although the sample size precludes a definitive statement about safety and efficacy, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach.
Abstract 6015: Percutaneous Coronary Intervention in Human Immunodeficiency Virus Infection
Authors: Xiushui Ren, Marina Trilesskaya, Damon M Kwan, Kim Nguyen, Richard E Shaw, Peter Y Hui
Journal: Circulation (2008)

Background: Human immunodeficiency virus (HIV) patients who undergo percutaneous coronary intervention (PCI) have a substantial risk of recurrent cardiac events. Outcome data in HIV patients who receive drug-eluting stents (DES) are limited. We hypothesized that HIV patients who undergo PCI with DES have less recurrent cardiac events compared with HIV patients with bare metal stents (BMS). Methods: We evaluated 94 consecutive HIV patients and 94 age- and sex-matched non-HIV patients who underwent PCI with stents between January 2000 and July 2007. Clinical, laboratory, and angiographic data were obtained by chart review. Major adverse cardiovascular events (MACE), defined as cardiovascular death, nonfatal myocardial infarction, and coronary revascularization, were adjudicated by two independent physicians, and Kaplan-Meier survival analysis was performed. Results: Of the 94 HIV patients, 53 had DES and 41 had BMS. Of the 94 control patients, 45 had DES and 49 had BMS. HIV patients had lower rates of diabe...
Circulating miRNA Biomarkers for Schizophrenia?
Authors: Murray J. Cairns
Journal: American Journal of Psychiatry (2015)

The Psychiatric Genomics Consortium recently derived a significant ensemble of common variants through its landmark mega genome-wide association study of schizophrenia (1).While this provides the foundations for variant profiling and the emergence of trait biomarkers, the predictive power of polygenic risk scoring defined by receiver-operating characteristic curve analysis is reported to be below the threshold for clinical utility (2).As an alternative, other nucleic acids, proteins, and various metabolites could support predictive function or serve as "state" biomarkers in the personalized management of schizophrenia (3).In this issue, Wei et al. ( 4) explore the potential of circulating serum microRNA (miRNA) levels to inform schizophrenia diagnosis and antipsychotic drug-associated remission.The authors extracted RNA from plasma collected from a large group of subjects with psychiatric illness (N5726)-mostly confirmed cases of schizophrenia-and control subjects (N5400) matched for age, gender, smoking history, and education level.The analysis of these samples was divided into discovery, validation, and follow-up cohorts (Figure 1).In the discovery phase, plasma RNA from 150 case subjects and 150 control subjects were each pooled and subjected to both small RNA sequencing (sRNA-seq) and miRNA TaqMan Low Density Array (TLDA) analysis.The authors then selected a subset of differentially expressed miRNAs (schizophrenia/control pooled plasma) with more than a twofold difference by sRNA-seq and a 10-fold difference by TLDA that were consistent by direction on each platform.These criteria yielded eight were then analyzed separately in the 300 individual samples of the discovery cohort by targeted quantitative polymerase chain reaction (qPCR) analysis.Under these conditions, allowing the full heterogeneity of the discovery set to be accounted for, only two molecules, miR-130b and miR-193a-3p, remained significantly altered in the schizophrenia group compared with the control group.Fortunately, the disease-associated up-regulation of these molecules was robust and was supported in a large validation sample consisting of another 400 case subjects and 213 control subjects.The elevated levels of these two miRNAs were shown to be relatively specific to schizophrenia, as no significant difference was observed between 400 control subjects and 162 subjects with nonschizophrenia psychiatric disorders, including major depression, anxiety, bipolar disorder, and other atypical psychiatric diseases.The 400
Tumor-Associated Antigen in Human Pancreatic Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Duane R. Schultz, Adel A. Yunis
Journal: JNCI Journal of the National Cancer Institute (1979)

New Zealand White rabbits were immunized with saline extracts of 1) a human pancreatic cancer cell line (MIA PaCa-2) 2) human pancreatic tumors excised from Swiss nu/nu mice, or 3) human pancreatic cancer tissue. Solid-phase immunoadsorbents rendered the resulting antisera specific. The antisera, tested by double immunodiffusion and counterimmunoelectrophoresis (CEP), detected the pancreatic antigen in saline extracts of human pancreatic carcinoma, human fetal pancreas, MIA PaCa-2 cells, a second human pancreatic cancer cell line (PANC-1), and nude mouse pancreatic tumors, but not in saline extracts of normal human pancreas and a number of other normal tissues, in normal human sera, or in sera from patients with active inflammatory disease. The antisera did not react with alpha-fetoprotein and carcinoembryonlc antigen. Sera of patients with pancreatic cancer and other neoplastic and nonneoplastic disorders were tested in CEP with two antisera: rabbit anti-MIA PaCa-2 and rabbit anti-human pancreatic carcinoma. Although both antisera detected the pancreatic antigen in 65–70% of the patients with biopsy-confirmed pancreatic carcinoma, the antihuman pancreatic carcinoma serum was less reactive with sera from patients having disorders not involving the pancreas. Rabbit anti-MIA PaCa-2 serum added to 5-day-old washed and fixed MIA PaCa-2 cells, followed by fluorescein-labeled goat antlrabblt serum, resulted in strong fluorescence located on the nuclear membranes. Additional antigen was released from saline-extracted cell membranes after treatment with Triton X-100. The estimated molecular weight of the tumor-associated pancreatic antigen was between 900×103 and 1,000×103 daltons. The antigen migrated in the β1 to α2 regions in agarose electrophoresis and was destroyed by 10% perchloric acid or by boiling.
Ventilatory restrictive impairment in thalassemic patients: Gender differences and correlation with hypogonadism and iron overload
Authors: S. Roggero, L. Zito, A. Piga, C. Ciacco, M. Guglielmo, M.V. de Vita, R. Torchio
Journal: European Respiratory Journal (2012)

BACKGROUND and AIM  Ventilatory restrictive (RES) impairment has been described in β-thalassemia, but no evidence exists on the causal mechanism. We investigated relationships among lung function, iron overload and clinical parameters in a homogeneous series of β-thalassemia major adult patients.  METHODS  We studied 79 patients (males M/ females F 44/35; age 34.5±6.8 years) with β-thalassemia major on regular transfusion and iron chelation. Iron overload was assessed by serum ferritin, liver iron concentration (LIC) by SQUID susceptometry, cardiac iron by MRI T2*. Lung volumes, diffusion capacity, chelator drugs, hypogonadism (H), hypothyroidism and osteoporosis were evaluated in stable hematologic conditions.  RESULTS  30/79 pt (38%) [ 21/44 (47.7%) M and 9/35 (25.7%) F] showed RES, 6 bronchial obstruction with no gender differences (3M 3F). In F LIC was higher 2249±903 vs 1497±553 mgFe/gliver dw; p  CONCLUSIONS  RES is present in 1/3 of well compensated adult thalassemic (M/F 1.88). Iron (LIC) was higher in RES F vs normals and H males have higher MRI T2*. Different gender impact of H on lung and chest growth, severity and efficacy of replacement therapy can explain data but the involved mechanisms is still unclear.
Randomized, Placebo-Controlled Trial of Paroxetine Versus Imipramine in Depressed HIV-Positive Outpatients
Authors: Andrew J. Elliott, Karina K. Uldall, Karen Bergam, Joan Russo, Keith Claypoole, Peter P. Roy-Byrne
Journal: American Journal of Psychiatry (1998)

This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection.Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12.Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%).Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.
Effect of roflumilast on lung function: Results from 180-days study in subjects With severe COPD
Authors: Mykola Ostrovskyy, Iryna Savelikhina, Oleksandr Varunkiv, Mariana Kulynych-Miskiv, Galyna Korzh
Journal: European Respiratory Journal (2013)

Background. In Ukraine the problem of chronic obstructive pulmonary disease (COPD) is extremely pointed. In particular, over the last decade, the incidence rate of COPD (before 2004 - chronic obstructive bronchitis) has increased by 6.9%, while the proportion among newly diagnosed diseases was about 38.0%  Aim. The purpose of this study was to investigate the effects of 500 μg roflumilast, taken once daily for 180 days on pulmonary function tests on abase of COPD treatment according to GOLD.  Materials and methods. Spirometry is the best way of detecting the presence of airway obstruction and it was perfomed using Spirocom (Kharkov, Ukraine) in 151 patients before and at 180 day of treatment with roflumilast.  Results. Compared with the group of patients, who did not use roflumilast, FEV1 consistently increased in 1.28 times (p 0.05), FEV1/FVC in 1.21 times.  Conclusions. Roflumilast was associated with significant improvements in lung function in patients with severe COPD after 180 days of treatment.
Postoperative Nomogram for Disease Recurrence After Radical Prostatectomy for Prostate Cancer
Authors: Michael W. Kattan, Thomas M. Wheeler, Peter T. Scardino
Journal: Journal of Clinical Oncology (1999)

Although models exist that place patients into discrete groups at various risks for disease recurrence after surgery for prostate cancer, we know of no published work that combines pathologic factors to predict an individual's probability of disease recurrence. Because clinical stage and biopsy Gleason grade only approximate pathologic stage and Gleason grade in the prostatectomy specimen, prediction of prognosis should be more accurate when postoperative information is added to preoperative variables. Therefore, we developed a postoperative nomogram that allows more accurate prediction of probability for disease recurrence for patients who have received radical prostatectomy as treatment for prostate cancer, compared with the preoperative nomogram we previously published.By Cox proportional hazards regression analysis, we modeled the clinical and pathologic data and disease follow-up for 996 men with clinical stage T1a-T3c NXM0 prostate cancer who were treated with radical prostatectomy by a single surgeon at our institution. Prognostic variables included pretreatment serum prostate-specific antigen level, specimen Gleason sum, prostatic capsular invasion, surgical margin status, seminal vesicle invasion, and lymph node status. Treatment failure was recorded when there was either clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on this set of men and a separate sample of 322 men from five other surgeons' practices from our institution.Cancer recurrence was noted in 189 of the 996 men, and the recurrence-free group had a median follow-up period of 37 months (range, 1 to 168 months). The 7-year recurrence-free probability for the cohort was 73% (95% confidence interval, 68% to 76%). The predictions from the nomogram appeared to be accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (ie, a comparison of the predicted probability with the actual outcome) of 0.89.A postoperative nomogram has been developed that can be used to predict the 7-year probability of disease recurrence among men treated with radical prostatectomy.
A bench study to investigate the effect of heated humidification on patient-ventilator asynchrony (PVA) in patients with chronic obstructive pulmonary disease (COPD) during non-invasive ventilation (NIV)
Authors: Swapna Mandal, Michelle Ramsay, Eui-Sik Suh, John Moxham, Nicholas Hart
Journal: European Respiratory Journal (2013)

INTRODUCTION: The use of heated humidification(HH) during NIV is controversial. HH could increase patient-ventilator asynchrony (PVA) by increasing dead space and adversely affecting triggering. We hypothesised that HH would increase PVA, leading to increased neural respiratory drive (NRD) and patient discomfort. METHODS: 12 COPD patients established on NIV were enrolled. 3 modes of NIV and humidification were applied in a random order: No humidification (NH); heated humidification (HH); and cold passover humidification (CH) (MR850 Fisher Paykel, NZ) for 30 minutes. Visual analogue scores (VAS), parasternal electromyography (EMGpara), mask pressure and respiratory inductance plethysmography were monitored throughout. RESULTS: 8 males, mean age 70.9±7 years, and FEV1 0.68±0.33L were studied. The proportion of total asynchronies was greater in the CH arm (p=0.17), as was the proportion of patients with asynchrony index (AI) >10% (p=0.23, Figure 1). There were no differences in VAS comfort, oronasal dryness or synchronisation between the 3 groups. NRD decreased significantly between baseline and NH, however, there was no difference between the 3 modes of NIV and humidification(figure 1). CONCLUSION: HH does not increase PVA during NIV in COPD.

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High-Dose Interferon Alfa-2b Does Not Diminish Antibody Response to GM2 Vaccination in Patients With Resected Melanoma: Results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696
Authors: John M. Kirkwood, Joseph Ibrahim, David H. Lawson, Michael B. Atkins, Sanjiv S. Agarwala, Keirsten Collins, Ruth Mascari, Donna M. Morrissey, Paul B. Chapman
Journal: Journal of Clinical Oncology (2001)

High-dose interferon alfa-2b (IFNalpha2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNalpha2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNalpha2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies.This trial enrolled 107 patients with resectable high- or very high-risk melanoma (AJCC stages IIB, III, and IV).The results demonstrate that IFNalpha2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNalpha2b and GMK is well tolerated in this patient population.Cox analysis of the results of the combination with IFNalpha2b show improvement in the relapse-free survival of patients with very high-risk melanoma (including those with resectable M1 disease).
Acute effects of volume-oriented incentive spirometry on chest wall kinematics in patients chronic stroke
Authors: Illia Lima, Gardênia Ferreira, Tânia Campos, Rodrigo Melo, Elis Emanuelle, Rêncio Florêncio, Guilherme Fregonezi
Journal: European Respiratory Journal (2012)

To study the acute effects of incentive spirometry (IS) volume-oriented on chest wall kinematics in chronic stroke patients and healthy subjects.

Volume of chest wall (CW), abdominal (ab), abdominal rib cage (RCab) and pulmonary rib cage (RCp) compartment were assessed in 20 chronic stroke patients (experimental group,EG) age 56±9.7 years old, FVC%:81.5±10.9 % and FEV1/FVC%:80.5 ±9.7 and 20 age-matched healthy subjects (control group,CG), age 56.5±10.3 years old, FVC%:95±6.8% (p=0.0028) and FEV1/FVC%:80.5 ±8.4 by Optoelectronic Plethysmography. Protocol comprise 3 moments: quite breathing (QB), volume-oriented IS (3 series/10 repetitions) and recovery quite breathing (rQB).The tidal volumes of chest wall in EG was lower compared to the CG, in QB (0.4vs0.61L), IS (1.8vs2.3 L) and rQB (0.4vs0.5 L) (p<0.0001). The tidal volume increase in chest wall 75% in EG and 73.3% CG during IS. Different pattern of breathing were found in tidal volume in EG compared to CG on ab compartment: QB(54.1%vs43.7%), IS(43.3%vs40.9%) and rQB(48.9% vs. 46.2%); RCab compartment, QB(13.8%vs16.8%), IS(19%vs20.6%) and rQB(15.2%vs17.2%) and RCp compartment, QB(30.7%vs37.9%), IS(37.7%vs39.9%) rQB(32.9%vs37.3%). Right and left hemithorax volume were different in EG, QB (ΔVt=0.06±0.04 ml vs 0.02±0.02 ml, p=0.002), IS(ΔVt=0.09 ±0.07 ml vs. 0.07±0.05 ml) and rQB(ΔVt= 0.07±0.07 vs 0.02±0.03 ml) independent of stroke side impairment.

Chest wall volumes are decrease in patients with chronic stroke. IS induces improvements in volume of chest wall in both groups; however, more pronounced in chronic stroke patients determining a breathing pattern similar that was observed in healthy subjects.
Lesson of the Week: Bilateral cataracts and glaucoma induced by long term use of steroid eye drops
Authors: J M Butcher, M Austin, J McGalliard, R Bourke
Journal: BMJ (1994)

The adverse effects of topical steroid administration to the eye are well known and include glaucoma, cataract, exacerbation of corneal infection, and systemic effects secondary to systemic absorption.1,2 Previous reports have highlighted the potential reactivation or exacerbation of herpes simplex keratitis, together with an increased risk of other infections.3,4 We report a case of steroid induced glaucoma and cataracts (with irreversible visual loss) following prolonged unsupervised administration of topical steroid eyedrops.

A 47 year old woman presented to the accident and emergency department with a chronic history of irritable eyes, a right upper lid chalazion, and decreasing vision over three months. The ophthalmic history was of left amblyopia and an episode of acute anterior uveitis several years previously. This uveitis had been treated at St Paul's Eye Hospital with topical steroids for four weeks. The only relevant medical history was of hypothyroidism.

On examination her best corrected visual acuities were 6/36 in the …
Abediterol has higher bronchodilatory potency and reduced cardiac effects versus other long-acting β2-agonists in dogs
Authors: Amadeu Gavaldà, Jose Luis Montero, Mònica Aparici, Carlos Puig, Christopher Doe, Montserrat Miralpeix
Journal: European Respiratory Journal (2014)

Background   Abediterol (LAS100977) is a novel, long-acting, inhaled β 2 -agonist in development for COPD and asthma. We investigated the potency, duration of action (DoA) and safety index of abediterol vs olodaterol and vilanterol in beagle dogs.   Methods   This vehicle-controlled, latin-square, crossover study of anaesthetized dogs (n=4) investigated the response to acetylcholine (10 µg/kg iv) after administration of nebulized abediterol (0.03, 0.1, 0.3 and 1 µg/kg), olodaterol (0.1, 1 and 10 µg/kg) and vilanterol (3, 10 and 30 µg/kg). Airway resistance, heart rate (HR), and plasma glucose and potassium concentrations were assessed prior to and at 10, 20 and 30 minutes, and 1, 3, 6 and 24 hours post-administration. There was a ≥6 day washout between treatments. The safety index is the ratio of doses required for 40% inhibition of bronchoconstriction (ID 40 ) and 10% increase in HR.   Results   Abediterol had a lower ID 40  (0.06 µg/kg) than olodaterol (0.18 µg/kg) or vilanterol (2.87 µg/kg). Abediterol had a higher safety index (10.3) than olodaterol (4.9) and vilanterol (2.4). DoA at the highest dose of each drug devoid of HR effects was longer for abediterol (1 µg/kg, half-life 18.9±5.1 h) than olodaterol (1 µg/kg, 5.4±1.6 h) and vilanterol (10 µg/kg, 3.4±1.0 h). No changes in potassium concentration were observed. Transient changes in glucose concentration were observed at the highest dose of each compound.   Conclusion   In dogs, abediterol has a more potent bronchoprotective effect with longer DoA than olodaterol and vilanterol, and reduced HR effects. These results suggest abediterol may provide sustained bronchodilation with reduced potential for cardiac effects in humans.