tbuckley/cabot-search huggingface dataset:
Saline Flush: A Simple Method of Reducing Diazepam-Induced Thrombophlebitis
Authors: M K Dutt, R P H Thompson
Journal: Journal of the Royal Society of Medicine (1982)

Five hundred outpatients undergoing endoscopy were admitted into a controlled trial comparing the incidence of thrombophlebitis following intravenous diazepam administered in the usual way, with the effects of either a saline flush following the diazepam or diluting the drug with the patient's own blood before injection (‘barbotage’). The results were assessed using a questionnaire completed by patients two weeks after endoscopy; 80% replied. A saline flush reduced the incidence of local side effects, particularly pain ( P &lt; 0.05). ‘Barbotage’ gave the highest incidence of side effects. Saline flush is therefore recommended as a means of reducing the thrombophlebitis which may follow intravenous diazepam.
Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma.
Authors: A Recht, S M Pierce, A Abner, F Vicini, R T Osteen, S M Love, B Silver, J R Harris
Journal: Journal of Clinical Oncology (1991)

We retrospectively analyzed the likelihood of regional nodal failure (RNF) for 1,624 patients with stage I or II invasive breast carcinoma treated with conservative surgery and radiotherapy (RT) at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. The median follow-up time was 77 months. RNF was the first site of failure for 38 of the 1,624 patients (2.3%). The incidence of axillary failure for patients undergoing axillary dissection (AXD) who were irradiated to the breast only was 2.1% (nine of 420) for patients with negative nodes and 2.1% (one of 47) for patients with one to three positive nodes. The incidence of supraclavicular failure in these two groups was 1.9% (eight of 420) and 0% (zero of 47), respectively. The incidences of axillary and supraclavicular failure in patients without clinically suspicious axillary involvement who did not have AXD but were treated with RT were 0.8% (three of 355) and 0.3% (one of 364), respectively. Despite various combinations of salvage surgery, RT, and systemic therapy, only 47% of patients (18 of 38) achieved complete regional control after nodal relapse. We conclude that RNF is uncommon in patients treated to the breast alone following an adequate AXD when the axillary nodes are negative or when one to three nodes are positive. RNF is also uncommon in patients with a clinically uninvolved axilla treated with nodal RT without AXD. Symptoms of RNF can be controlled in most but not all patients. Further study is needed to determine if the benefits of RT in preventing a small number of symptomatic RNF outweigh the potential toxicity for any subgroup of patients.
Peripheral blood Th17 cells and serum IL-17 levels in patients with D. pteronyssinus-induced late-phase asthmatic response
Authors: Ieva Bajoriuniene, Kestutis Malakauskas, Simona Lavinskiene, Jolanta Jeroch, Edita Gasiuniene, Astra Vitkauskiene, Raimundas Sakalauskas
Journal: European Respiratory Journal (2012)

Background. Biphasic cellular immune reaction which follows inhalation of allergen is the specific feature of allergic inflammation. Therefore, Th17 cells and IL-17 may have played a role in the development of the late-phase asthmatic response in patients with allergic asthma.

Objectives. To evaluate the percentage of Th17 cells in peripheral blood (PB) and serum IL-17 levels in patients with D. pteronyssinus -induced late-phase asthmatic response.

Methods. We studied 28 patients with allergic asthma who developed early-phase asthmatic response (EAR) (n=16) and late-phase asthmatic response (LAR) (n=12) after bronchial challenge with D. pteronyssinus . The control group included 10 healthy subjects (HS). PB collection was performed 24 h before as well as 7 h and 24 h after challenge. The percentage of Th17 cells was analyzed by FACS. Serum IL-17 levels were determined by ELISA.

Results. 

View this table:

Peripheral blood Th17 cells and serum IL-17 levels in patients with allergic asthma before and after bronchial challenge with D. pteronyssinus 





Conclusions. D. pteronyssinus -induced late-phase asthmatic response in patients with allergic asthma is associated with increased percentage of Th17 cells in PB and elevated serum IL-17 levels.
Surgical lung biopsy - Gold standard for diagnosis of idiopathic interstitial pneumonia?
Authors: Olena Semendyayeva, Nadiya Monogarova, Vladimyr Gavrisyk, Evgeniya Merenkova, Sergey Leshenko
Journal: European Respiratory Journal (2012)

The current classification of idiopathic interstitial pneumonia (IIP) is based on the account of the specificities of the clinical picture, radiological and pathological features. This raises the question of how much the necessity of verification of the diagnosis of IIP data pathologic study biopsy or autopsy lung material. To answer this question, we asked three highly-skilled pathologist with considerable experience in pulmonology, to conduct an independent analysis of the same histological lung tissue of patients with various forms of IIP. For the analysis of slides, presented 73 patients with IIP. Material for histological study was obtained during open and videotorakoskopic lung biopsy and at autopsy.According to clinical studies and results of computed tomography high-resolution was found clinical diagnosis of idiopathic fibrosing alveolitis (IFA) for the pathomorphological study, nonspecific interstitial pneumonia (NSIP), lymphoid interstitial pneumonia (LIP), cryptogenic organizing pneumonia (COP) and respiratory bronchiolitis associated with interstitial lung disease (RB-ILD). Match the clinical diagnosis with the conclusions of three experts were only in 15 cases (20.5%), two experts in 35 (47.9%) and one - in 15 cases (20.5%). In most cases, differences in interpretation of histological data did not go beyond the group of IIP. Differentiated forms of IIP in practice pulmonology very difficult. At the same time, identification of each form of IIP is not an end in itself, it is essential if accurate diagnosis determines the treatment tactics. In our opinion, surgical biopsy of the lungs is necessary in the differential diagnosis of IIP with other interstitial lung diseases.
LSC 2014 abstract - Azithromycin lowers mucin production by increasing FOXA2 expression in an IL-13-induced MUC5AC expression model in human bronchial epithelial cells
Authors: Tinne Mertens, Jasmijn Schrumpf, Renate Verhoosel, Pieter Hiemstra, Christian Taube
Journal: European Respiratory Journal (2014)

Airway mucus plays a critical role in clearing inhaled particles and pathogens. However, goblet cell metaplasia and mucus hypersecretion are important characteristics of inflammatory lung diseases, including cystic fibrosis, asthma and chronic obstructive disease. Interleukin 13 (IL-13) is a Th2 cytokine that induces goblet cell metaplasia and mucus production in human bronchial epithelial cells. Because macrolide antibiotics are known to have anti-inflammatory and immune-modulatory properties in addition to being antimicrobial, the aim of this study was to investigate the effect of the macrolide azithromycin (AZM) on signaling mechanisms involved in IL-13-induced MUC5AC expression in human bronchial epithelial cells.  Normal human bronchial epithelial cells cultured at an air liquid interface were exposed to 5 ng/ml or 10 ng/ml IL-13 with or without AZM during 5 days or 2 weeks. After exposure cells were lysed and MUC5AC expression was analysed by quantitative RT-PCR. Additionally, the expression of SPDEF and FOXA2, important factors involved in IL-13-induced MUC5AC expression was analysed.  Exposure to IL-13 alone increased MUC5AC expression, which was inhibited by addition of AZM. SPDEF expression was increased by IL-13 exposure whereas FOXA2 expression was decreased by IL-13. AZM did not affect IL-13 induced SPDEF expression, but did prevent the IL-13 mediated decrease of FOXA2 expression.  These results suggest that AZM controls MUC5AC expression by increasing FOXA2 expression, a negative regulator of MUC5AC. Further studies are needed to demonstrate the functional involvement of increased FOXA2 expression in the effects of AZM.
Cellular and molecular regulation of the activation of mammalian primordial follicles: somatic cells initiate follicle activation in adulthood
Authors: Hua Zhang, Kui Liu
Journal: Human Reproduction Update (2015)

BACKGROUNDThe first small follicles to appear in the mammalian ovaries are primordial follicles. The initial pool of primordial follicles serves as the source of developing follicles and oocytes for the entire reproductive lifespan of the animal. Although the selective activation of primordial follicles is critical for female fertility, its underlying mechanisms have remained poorly understood.
Repeatable Battery for the Assessment of Neuropsychological Status as a Screening Test in Schizophrenia, II: Convergent/Discriminant Validity and Diagnostic Group Comparisons
Authors: Mary P. Hobart, Richard Goldberg, John J. Bartko, James M. Gold
Journal: American Journal of Psychiatry (1999)

In a companion article in this issue of the Journal, the authors presented data suggesting that the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is sensitive to the types of impairments observed in schizophrenia, correlates highly with standard measures of intelligence and memory, and is related to employment status in a group of patients with schizophrenia drawn from a tertiary care research center. The objectives of the current study were 1) to determine if evidence of the convergent validity of the RBANS could be replicated in a diagnostically heterogeneous sample drawn from a public mental health system, 2) to examine the relationship of the RBANS to a broad neuropsychological battery, and 3) to compare the performance of patients with schizophrenia and patients with bipolar disorder on a neuropsychological battery and the RBANS.The RBANS and a standard neuropsychological battery, including the WAIS-III and Wechsler Memory Scale, 3rd ed. (WMS-III), were given to 150 patients drawn from a larger study of vocational rehabilitation.Correlations of RBANS total scores with WAIS-III and WMS-III variables were highly similar across study groups. The RBANS correlated highly with a composite z score derived from 22 standard measures of IQ, memory, language, motor, attention, and executive function. Principal component analyses of the neuropsychological battery resulted in a six-factor solution: the RBANS correlated most highly with a general ability factor and had limited correlations with measures of motor performance, vigilance, and executive function. Patients with schizophrenia demonstrated greater deficits on the neuropsychological battery and the RBANS than patients with bipolar disorder.These data suggest that the RBANS is a useful screening instrument for assessing the severity of cognitive impairment in psychiatric populations.
Inflammation in COPD patients before and after roflumilast treatment
Authors: María Inés Vargas-Rojas, Helena Solleriro-Villavicencio, Alejandra Ramírez-Venegas, Rafael Hernández-Zenteno, Oliver Pérez-Bautista, Abraham Ziga-Martinez, Roger Quintana-Carrillo, Fernando Dueñas-Morales, Rasúl Sansores-Martínez
Journal: European Respiratory Journal (2014)

Background.Most of the clinical features of COPD are determined by cytokines, chemokines and growth factors. Roflumilast is a phosphodiesterase type 4 inhibitor, producing an anti-inflammatory effect. It is administered orally as a single daily dose, and it was developed as a treatment to diminish chronic inflammation of COPD patients, although its effect on the level of cytokines and chemokines involved in the polarization of the CD4+ T cells is unknown  Aim. Determine if Roflumilast is able to reduce the concentration of pro-inflammatory cytokines and chemokines, impacting on the polarization of the CD4+ subpopulations  Material and methods. Twenty-four patients with COPD diagnose (GOLD guidelines), candidates to Roflumilast treatment. Peripheral samples were taken, a baseline simple and another 8 weeks after treatment. Through flow cytometry the proportion of CD4+ T cells were defined. Serum cytokines and chemokines were quantified through the Luminex system  Results. All the subjects had a low respiratory function (FEV1 28 (18-36)%) After Roflumilast treatment patients showed a significant reduction of pro-inflammatory cytokines (IL-1b, IL-6 e IL-17) and chemokines (IL-8, eotaxin, IP-10 y MCP-1). Th17 were reduced (pre 5.8±1.5, post 5.4±1.6, p=0.0367) and Treg cells increased (pre 7.7±1.4, post 8.8±1.3, p=0.0000)  Conclusions. This study shows that Roflumilast is capable of reducing the concentration of pro-inflammatory cytokines and chemokines in a period as short as 8 weeks. During this time it can be observe decrease of Th17 cells and an increase of Treg cells that suggests a change in the microenvironment that might lead to the development of certain anti-inflammatory mechanisms.
Phase II clinical trial with a second generation, GM-CSF encoding, oncolytic herpesvirus in unresectable metastatic melanoma
Authors: N. N. Senzer, H. Kaufman, T. Amatruda, M. Nemunaitis, G. Daniels, J. Glaspy, H. Goldsweig, R. S. Coffin, J. Nemunaitis
Journal: Journal of Clinical Oncology (2009)

9035 Background: OncoVEX GM-CSF is a an oncolytic HSV, encoding GM-CSF . We recently completed a phase II trial involving 50 advanced melanoma patients (stage IIIc and IV) with at least one injection accessible lesion, including by ultrasound. Methods: Patients received a single IT injection of 10 6 pfu/ml apportioned between 10 or less injectable tumors, followed 3 wks later by 24 or less sequential injections of 10 8 pfu/ml every 2 wks until clinically significant disease progression, or overall or injectable lesion complete response. Response (RECIST modified to allow progression before response and biopsy of residual masses) and survival were monitored. Results: All 50 pts have been enrolled and are evaluable (Stage IIIc, n=10; IV M1a, n=16; IV M1b, n=4; IV M1c, n=20). A median of 6 injections were administered. Adverse effects were limited and generally involved transient flu-like symptoms. Both injected and uninjected regional and distant disease demonstrated response including clearly documented responses at uninjected visceral sites. The overall response rate was 26% (8 CR, 5 PR); 10 responses have been maintained for &gt;6 months and 2 are ongoing at &lt;6months, the longest currently being at 35 months from first dose. 93% of patients (14 of 15) with PR, CR or surgical CR remain alive. Ten additional patients had SD for &gt;3 months. Kaplan Meier one year survival is 61% overall, 58% stage IV only, 48% for Stage IV M1c. The median OS is 16+ months. Conclusions: The 1-year survival and durable objective response rate are encouraging. Responses of distant and visceral disease provide further compelling evidence of systemic effectiveness. This, combined with a limited toxicity profile, suggests OncoVEX GM-CSF is a promising treatment for metastatic melanoma. A phase III clinical trial is planned. [Table: see text]
Abstract 255: Low Endothelial Shear Stress (ESS) is Responsible for the Heterogeneity and Severity of Coronary Atherosclerotic Plaques: An In-Vivo IVUS Natural History Study
Authors: Yiannis S Chatzizisis, Michael Jonas, Ahmet U Coskun, Anna-Maria Spognardi, Adam Groothuis, Mamoru Nanasato, Ross B Gerrity, William Daley, Campbell Rogers, Charles L Feldman, Peter H Stone
Journal: Circulation (2006)

Objectives:  Atherosclerotic lesions are multifocal and progress at different rates, despite exposure to the same systemic risk factors. We investigated the potential role of focal areas of low ESS on the localization and severity of plaque formation.   Methods:  Twenty seven streptozotocin-induced diabetic hyperlipidemic swine were studied. Serial IVUS with 3D reconstruction of each coronary artery was performed at 4, 8, 23 and 30 wks. Plaque severity by IVUS was defined by plaque thickness (0.4 – 0.7 mm vs 0.8 –1.0 mm vs >1.0 mm). Local ESS throughout each artery was determined from computational fluid dynamics. Plaque-free subsegments by IVUS (average length 5 mm) with low ( 2.4 Pa) ESS were identified in each artery at 23 wks; and assessed by histology at 30 wks. Plaque severity by histology was defined by intimal/media ratio and maximum intimal thickness.   Results:  Plaque developed and progressed after 8 weeks, with remarkable heterogeneity of number and severity of plaque by IVUS over time (Fig A). Histology indicated that subsegments (n=43, average=4.2 per artery) with low ESS at baseline were associated with significantly higher intima/media ratio and maximum intimal thickness at follow-up compared to areas with moderate or high ESS (p   Conclusions:  Low ESS determines the location and severity of coronary artery plaque. The heterogeneity of the natural history of atherosclerotic plaques is related to the local ESS environment. Ongoing analyses focus on the role of local ESS on vascular remodeling, plaque inflammation and neovascularization over time.
A BAFF Receptor His159Tyr Mutation in Sjögren's Syndrome–Related Lymphoproliferation
Authors: Aristea Papageorgiou, Clio P. Mavragani, Andrianos Nezos, Elias Zintzaras, Luca Quartuccio, Salvatore De Vita, Michael Koutsilieris, Athanasios G. Tzioufas, Haralampos M. Moutsopoulos, Michael Voulgarelis
Journal: Arthritis & Rheumatology (2015)

Objective To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF‐R) in patients with Sjögren's syndrome (SS). Methods The BAFF‐R His159Tyr mutation was evaluated using polymerase chain reaction (PCR)–based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS‐lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real‐time PCR and Western blotting were performed for the quantification of both NF‐κB1 and NF‐κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS‐lymphoma carrying the mutation (SS‐lymphoma–BAFF‐R His159Tyr –derived B cells) compared to B cells from patients with SS‐lymphoma who were not carriers of the mutation and healthy controls. Results Both the SS‐lymphoma and SS‐nonlymphoma patient subgroups exhibited significantly higher frequencies of the His159Tyr BAFF‐R mutation compared to healthy controls (8.6% of SS‐lymphoma patients and 6.2% of SS‐nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159Tyr BAFF‐R mutation in SLE and RA patients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa‐associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS‐related MALT lymphoma in the younger age at onset (age &lt;40 years) group in the presence of the BAFF‐R mutation was 6.1 (95% confidence interval 2.0–18.7) ( P &lt; 0.01). Expression of NF‐κB at both the mRNA and protein level was up‐regulated in SS‐lymphoma–BAFF‐R His159Tyr –derived B cells. Conclusion This study identifies an increased prevalence of the BAFF‐R His159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF‐R His159Tyr –mediated activation of the alternate NF‐κB pathway might contribute to the pathogenesis of SS‐related lymphoproliferative disease.
Phase I clinical and pharmacokinetic evaluation of high-dose mitoxantrone in combination with cytarabine in patients with acute leukemia.
Authors: E J Feldman, D S Alberts, Z Arlin, T Ahmed, A Mittelman, P Baskind, Y M Peng, M Baier, P Plezia
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the maximally tolerated dose of mitoxantrone in combination with cytarabine in patients with acute leukemia and advanced phases of chronic myelogenous leukemia (CML), and to assess the pharmacokinetics of high-dose mitoxantrone in this patient population. PATIENTS AND METHODS In a phase I study, 68 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and accelerated- and blastic-phase CML received induction therapy consisting of cytarabine 3 g/m2 by infusion over 3 hours daily for 5 days, with escalating doses of mitoxantrone 40 to 80 mg/m2 over 1 to 2 days by intravenous infusion over 15 minutes. Mitoxantrone pharmacokinetics were evaluated by high-performance liquid chromatography (HPLC) in 15 patients given a single dose of mitoxantrone ranging from 40 to 80 mg/m2 in combination with cytarabine. RESULTS Severe, but reversible hyperbilirubinemia (&gt; three times normal) was considered the dose-limiting toxicity, and was observed in 25% of all patients and in 35% of those who received 70 to 80 mg/m2 of mitoxantrone. Other extramedullary toxicity, including cardiac dysfunction, was mild. Myelosuppression was universal and the median time to complete remission (CR) was 28 days (range, 19 to 77). The CR rate for previously untreated and relapsed patients with AML was 85% (17 of 20) and 38% (seven of 18), respectively. Eighty-three percent (15 of 18) of patients with ALL achieved a CR, including all patients with previously untreated disease. Eight of 12 patients with advanced-phase CML achieved a CR. No significant changes in mean mitoxantrone plasma elimination rates (ie, terminal plasma half-life and total-body clearance rate) occurred as the mitoxantrone dose doubled, indicating linear pharmacokinetics. CONCLUSIONS The recommended phase II dose of mitoxantrone is 80 mg/m2 administered over 15 minutes as a single intravenous infusion in combination with cytarabine 3 g/m2/d for 5 days. At this dose, high concentrations of mitoxantrone are achievable in vivo to levels that have been shown to be extremely cytotoxic in vitro.
Live rubella virus vaccine long-term persistence as an antigenic trigger of cutaneous granulomas in patients with primary immunodeficiency
Authors: C. Bodemer, V. Sauvage, N. Mahlaoui, J. Cheval, T. Couderc, S. Leclerc-Mercier, M. Debré, I. Pellier, L. Gagnieur, S. Fraitag, A. Fischer, S. Blanche, M. Lecuit, M. Eloit
Journal: Clinical Microbiology and Infection (2014)
Diabetes Drug Helps Promote Weight Loss in Obese Patients
Authors: Anita Slomski
Journal: JAMA (2015)

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