tbuckley/cabot-search huggingface dataset:
Smoking cessation treatment for COPD smokers
Authors: Carlos A. Jimenez Ruiz, Ana Maria Cicero Guerrero, Maria Luisa Mayayo Ulibarri, Maria Isabel Cristobal Fernandez, Gema Lopez Gonzalez
Journal: European Respiratory Journal (2011)

We reviewed medical histories of all COPD patients who were treated in our Unit between January 2004 and 2010. All patients received both psychological and pharmacological treatment (NRT, varenicline or bupropion). Medical and smoking histories were obtained during the baseline visit. A Quit date was chosen and therapy was begun. In all follow-up visits, patients received treatment, and control of abstinence and monitoring of adverse effects were carried out. The treatment was free of charge.  The following aspects were assessed: continuous abstinence rate (CAR) between week 9 and 12 and CAR between week 9 and 24, both defined by not smoking over those periods of time. Levels of CO of 10 ppm or less were required.  472 COPD smokers received treatment, average age 58,3 (9,8), and 65% of them were male. Average number of cigarettes a day, number of smoking years and number of pack-year were 29,7 (13,4), 40,5 (9,9) y 59,1 (30,2), respectively. The average rate on FTND-questionnaire was 7,4 (2,1). NRT was prescribed in 233 (49%), Bupropion in 45 (9,5%),Varenicline in 190 (40%), and 4 (1,5%) of them did not received treatment.Global effectiveness was: CAR from week 9 to 12 was met by 54,3%, and CAR from week 9 to 24 was met by 48,5%. Taking into consideration the kind of treatment used, CAR from week 9 to 24 were 44,1%, 60% y 61% for nicotine patches, bupropion and varenicline respectively. Significant differences were observed between varenicline and nicotine patches. OR: 1,98 (1,25-3,12); p:.003.  Good effectiveness of pharmacological treatments for COPD smokers.  Good safety pattern of smoking cessation pharmacological treatments for COPD smokers.  Varenicline gets better efficacy results than nicotine patches in this group of smokers.
A Phase III Study Of ASCT Vs Cyclophosphamide-Lenalidomide-Dexamethasone and Lenalidomide-Prednisone Maintenance Vs Lenalidomide Alone In Newly Diagnosed Myeloma Patients
Authors: Antonio Palumbo, Francesca Gay, Andrew Spencer, Francesco Di Raimondo, Adam Zdenek, Alessandra Larocca, Antonietta Pia Falcone, Lucio Catalano, Paola Finsinger, Scudla Vlastimil, Simona Aschero, Massimo Offidani, Anna Marina Liberati, Angelo Michele Carella, Maisnar Vladimir, Francesca Donato, Tommaso Caravita, Paolo Corradini, Roberto Ria, Stefano Pulini, Raffaella Stocchi, Concetta Conticello, Maria Teresa Petrucci, Roman Hajek, Mario Boccadoro
Journal: Blood (2013)
Efficacy of ciprofloxacin against resistant mucoid or non-mucoid P. aeruginosa isolated from non-cystic fibrosis bronchiectasis (NCFB) patients considering lung pharmacokinetics after ciprofloxacin DPI treatment
Authors: Sabine Obertegger, Gabriele Weskott, Petra Surdakowski, Martin Glenschek-Sieberth
Journal: European Respiratory Journal (2014)

Rationale : Ciprofloxacin dry powder for inhalation (DPI) is in Phase III development for chronic intermittent treatment of NCFB.  Objective:  To assess bactericidal activity of simulated ciprofloxacin DPI against resistant  P. aeruginosa  isolates through pharmacological studies.  Method : Resistant  P. aeruginosa  isolates (n=24) from NCFB patients with minimum inhibitor concentrations (MIC) ranging from 4 to 64mg/L were evaluated in time kill studies using maximum (120mg/L) or half maximum (60mg/L) sputum concentrations simulating levels expected after inhalation of 32.5mg ciprofloxacin DPI. Efficacy was assessed as reduction in log colony forming units (CFU). A subset of isolates (n=7) were evaluated in a hollow fiber (HF) model to simulate lung pharmacodynamics and determine bactericidal reductions over time.  Results : MIC dependent  P. aeruginosa  CFU reduction rates at maximum concentration ranged from 1 to 6 logCFU and at half maximum from 0.2 to 6 logCFU. A 3 logCFU reduction was observed in isolates with MIC≤32mg/L. In isolates with MIC 64mg/L, a 1 logCFU reduction was observed at maximum concentration. For isolates tested in the HF model, MIC dependent reduction rates were observed; time to display 3 logCFU reduction without regrowth in 10 hours in isolates with MICs from 4 to 8mg/L ranged from 9 to 45 minutes.  Conclusion : Sputum concentrations expected after inhalation of 32.5mg ciprofloxacin DPI resulted in bactericidal reduction of resistant  P. aeruginosa  isolates from NCFB patients. Clinical data in patients with resistant isolates is required to confirm these results.
Lithium Nephrotoxicity
Authors: GLEN S. MARKOWITZ, JAI RADHAKRISHNAN, NEERAJA KAMBHAM, ANTHONY M. VALERI, WILLIAM H. HINES, VIVETTE D. D'AGATI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria &gt;1.0 g/d in 41.7%. Nephrotic proteinuria (&gt;3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with &gt;50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria &gt;1.0 g/d ( P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values &gt;2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine &lt;2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine &gt;2.5 mg/dl at biopsy ( P = 0.008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.
Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults
Authors: Lauren J. Gleason, Eva M. Schmitt, Cyrus M. Kosar, Patricia Tabloski, Jane S. Saczynski, Thomas Robinson, Zara Cooper, Selwyn O. Rogers, Richard N. Jones, Edward R. Marcantonio, Sharon K. Inouye
Journal: JAMA Surgery (2015)

<h3>Importance</h3> Major postoperative complications and delirium contribute independently to adverse outcomes and high resource use in patients who undergo major surgery; however, their interrelationship is not well examined. <h3>Objective</h3> To evaluate the association of major postoperative complications and delirium, alone and combined, with adverse outcomes after surgery. <h3>Design, Setting, and Participants</h3> Prospective cohort study in 2 large academic medical centers of 566 patients who were 70 years or older without recognized dementia or a history of delirium and underwent elective major orthopedic, vascular, or abdominal surgical procedures with a minimum 3-day hospitalization between June 18, 2010, and August 8, 2013. Data analysis took place from December 13, 2013, through May 1, 2015. <h3>Main Outcomes and Measures</h3> Major postoperative complications, defined as life-altering or life-threatening events (Accordion Severity grade 2 or higher), were identified by expert-panel adjudication. Delirium was measured daily with the Confusion Assessment Method and a validated medical record review method. The following 4 subgroups were analyzed: (1) no complications or delirium; (2) complications only; (3) delirium only; and (4) complications and delirium. Adverse outcomes included a length of stay (LOS) of more than 5 days, institutional discharge, and rehospitalization within 30 days of discharge. <h3>Results</h3> In the 566 participants, the mean (SD) age was 76.7 (5.2) years, 236 (41.7%) were male, and 523 (92.4%) were white. Forty-seven patients (8.3%) developed major complications and 135 (23.9%) developed delirium. Compared with no complications or delirium as the reference group, major complications only contributed to prolonged LOS only (relative risk [RR], 2.8; 95% CI, 1.9-4.0); by contrast, delirium only significantly increased all adverse outcomes, including prolonged LOS (RR, 1.9; 95% CI, 1.4-2.7), institutional discharge (RR, 1.5; 95% CI, 1.3-1.7), and 30-day readmission (RR, 2.3; 95% CI, 1.4-3.7). The subgroup with complications and delirium had the highest rates of all adverse outcomes, including prolonged LOS (RR, 3.4; 95% CI, 2.3-4.8), institutional discharge (RR, 1.8; 95% CI, 1.4-2.5), and 30-day readmission (RR, 3.0; 95% CI, 1.3-6.8). Delirium exerted the highest attributable risk at the population level (5.8%; 95% CI, 4.7-6.8) compared with all other adverse events (prolonged LOS, institutional discharge, or readmission). <h3>Conclusions and Relevance</h3> Major postoperative complications and delirium are separately associated with adverse events and demonstrate a combined effect. Delirium occurs more frequently and has a greater effect at the population level than other major complications.
Physical activity in daily life in COPD after exercise training: Are there responders, and who are they?
Authors: Nidia A. Hernandes, Thaís Sant'Anna, Carlos A. Camillo, Vanessa S. Probst, Fabio Pitta
Journal: European Respiratory Journal (2012)

Background: Previous studies have shown that patients with chronic obstructive pulmonary disease (COPD) generally do not increase their level of physical activity in daily life (PADL) after short-lasting exercise programs. However, as PADL is influenced by several factors, there are individual patients who respond positively becoming more active in daily life. Aims: To study the proportion and profile of patients with COPD who become more active in daily life after a 12-week exercise training program (responders). Methods: 23 patients (15 men, 66±8yrs, FEV142±16%pred) completed an exercise training protocol (endurance and strength exercises, 3x/week, 12 weeks). PADL was assessed by an activity monitor (Sensewear®, BodyMedia) which registered the time spent in physical activities of at least moderate intensity (TPA>mod). Other assessments were socio-economic and functional status, quality of life, exercise capacity, respiratory and peripheral muscle force. Responders were those who increased TPA>mod after the protocol. Results: 12 patients (52%) were responders (TPA>mod 10[3-28]min/day pre vs. 32[10-38]min/day post; p=0.002; median[IQR]). The proportion of physically active patients (i.e. TPA>mod ≥30min/day) increased after the protocol (26% vs. 39%, p=0.01). Although responders and nonresponders had similar physical and functional capacity, responders tended to present exertional desaturation (p=0.076), lower age (p=0.055) and live alone (p=0.089). Conclusions: These preliminary findings suggest that around half of patients with COPD increase their level of PADL after a 12-week exercise training program. Responders tend to be younger, live alone and desaturate during exertion.
Metabolic Reduction of Benzidine Azo Dyes to Benzidine in the Rhesus Monkey2
Authors: Esther Rinde, Walter Troll
Journal: JNCI Journal of the National Cancer Institute (1975)

Rhesus monkeys were fed azo dyes derived from benzidine (a known human bladder carcinogen). The urinary excretion of free benzidine was assayed and compared to the amount excreted when benzidine itself was fed. A substantial amount of the dye fed was converted to free benzidine. Results indicate that the simple precaution in the use of only azo dyes manufactured from noncarcinogenic aromatic amines, e.g., aniline, for all consumer products appears prudent
Water transport in cultured cells from the rat inner medullary collecting duct.
Authors: J I Hubbard
Journal: Journal of the American Society of Nephrology (1996)

In this study, cells derived from rat inner medullary collecting duct formed a polarized monolayer when grown in wells on a membrane. When the membrane was sealed in an Ussing apparatus, the cells passed water from their apical to basolateral surfaces in the presence of an osmotic gradient. This was detected by the movement of the meniscus (1 mm = 1 microL) in a capillary tube connected to the basolateral chamber. The movements were measured by a travelling microscope, and the effects of vasopressin, oxytocin, and kappa opioids were explored at 37 +/- 1 degrees C. In the presence of vasopressin and oxytocin, water movement increased to between the threshold of 0.2 pM and the maxima of 100 pM (vasopressin) and 20 pM (oxytocin). Higher concentrations had a lesser effect (vasopressin) or no greater effect (oxytocin). It was possible to get a similar effect with each of two doses of 10 pM vasopressin at intervals as short as 3 min, but tachyphyllaxis lasting 70 min followed a dose of 20 pM oxytocin. The effects of vasopressin and oxytocin could be blocked completely by the cAMP antagonist adenosine-3',5'-cyclic monophosphorothioate Rp isomer. The benzenacetamide kappa agonist U-50488 had no effect on the response to 1 pM vasopressin but the kappa antagonist norbinaltorphimine significantly increased the effects of 1 pM vasopressin; this action was exerted earlier on in the initiation of water transport, as norbinaltorphimine did not affect the response to Sp-cAMPS, an activator of cAMP-dependent kinases.
Brain tumor-polyposis syndrome: two genetic diseases?
Authors: F Paraf, S Jothy, E G Van Meir
Journal: Journal of Clinical Oncology (1997)

PURPOSE AND DESIGN This report presents a comprehensive and statistical analysis of the brain tumor-polyposis (BTP) cases referred to as Turcot's syndrome in the literature. RESULTS BTP patients encompass a heterogeneous group that can be classified into two statistically distinct clinical entities based on phenotype of the polyps (P = .0001), presence of colorectal cancer (P = .0001), type of brain neoplasm, ie, glioma or medulloblastoma (P = .0001), presence of skin lesions (P = .0004) and cafe-au-lait spots (P = .0008), as well as consanguinity (P = .0135). CONCLUSION The first entity (BTP syndrome type 1) consists of patients who have glioma and colorectal adenomas without polyposis (non-FAP cases), and their siblings with glioma and/or colorectal adenomas. For these patients, we show that the patient's age at malignant glioma occurrence is less than 20 years (50 to 80 years in the general population), which strongly supports the existence of an underlying genetic cause. The neoplasms of these patients show DNA replication errors, which suggests a relationship with hereditary nonpolyposis colorectal cancer (HNPCC), a disease characterized by germline alterations in DNA mismatch repair genes. The second entity (BTP syndrome type 2) consists of patients with a CNS tumor that occurs in a familial adenomatous polyposis kindred (FAP cases). These patients carry germline mutations in the APC gene, which suggests that mutations in this gene might predispose to brain tumors. Risk analysis shows increased incidence of medulloblastoma in FAP patients, but APC mutations are not found in sporadic glioma or medulloblastoma. Therefore, further investigations should establish whether the occurrence of medulloblastoma in an FAP family represents a variant of FAP.
Lung clearance index differentiates children with poorly controlled asthma better than FEF2575: Data from the paediatric asthma genes and environment study
Authors: Helen Sheridan, Debbie Miller, Kenneth Macleod, Stephen Turner, Steve Cunningham
Journal: European Respiratory Journal (2011)

Introduction:  Lung Clearance Index (LCI) has been shown to differ between children with and without asthma. We have further examined relationships between LCI, spirometry and outcomes within a group of asthmatic children.   Methods:  Children with asthma were recruited to a national study. Assessment included respiratory and children9s asthma control questionnaires, spirometry, and for individuals recruited in Edinburgh, Multiple Breath Washout (MBW). Results are compared to previously obtained data from healthy controls.   Results:  63 asthmatic patients aged 5.1-16.5 years performed MBW. Controls included 66 children aged 5.0-16.1 years. Mean (SD) LCI in our asthmatic group was 6.7 (0.9) and was higher than in our healthy group, in which LCI was 6.3 (0.5) (p=0.007). The asthmatic group also had significantly worse FEF 2575  z score (p 1 ; FEV 1  did not correlate with LCI.  Patients with completely or well controlled asthma had significantly lower LCI (6.4) than those whose asthma was described as somewhat controlled or worse (6.9; p=0.02). There was no difference in FEV 1  or FEF 2575  between these groups. LCI also correlated with reported time that asthma affected school work (r=0.36; p=0.015) and use of salbutamol (r=0.33; p=0.03).   Conclusions:  Our cohort of children with asthma had significantly higher LCI compared to healthy children. LCI was also higher in patients whose parents reported poorer asthma control, something not evident for FEV 1  or FEF 2575 . LCI may be considered a better surrogate of symptom control than spirometry.
Increased Alkaline Phosphatase Activity—A Positive Histochemical Marker for Griseofulvin-Induced Mouse Hepatocellular Nodules234
Authors: Stanley Goldfarb, Thomas D. Pugh, Derek J. Cripps
Journal: JNCI Journal of the National Cancer Institute (1980)

Ductular and hepatocellular lesions were induced in 12 female Swiss Webster albino mice by a diet containing 2% griseofulvin fed to the mice for 4–17 months. In 6 of the mice fed griseofulvin for 10 or 11 months, three types of foci and nodules of hepatocytes persisted up to 6 months after discontinuation of the carcinogen. Type 1 foci were composed of large hepatocytes with abundant eosinophilic cytoplasm, wheras other much less frequent but larger nodules of basophilic hepatocytes were arranged in cellular (type 2) or more papiliary-trabecular (type 3) patterns. Hepatocytes in all types of foci and nodules showed uniformly increased amounts of histochemically demonstrable plasma membrane-associated alkaline phosphates activity. Foci and nodules showed fourteenfold to 25-fold higher [3H]thymidine labeling indices than did nonnodular hepatocytes. Of 5 type 3 nodules, 2 infiltrated adjacent liver tissue, which supported the view that the trabecular nodules were malignant. Because type 2 and type 3 nodules were far less frequent than were type 1 foci but also contained type 1 hepatocytes and because type 2 and type 3 nodules had higher labeling indices than did type 1 foci but shared with them a newly acquired histochemical characteristic, it was suggested that the type 1 hepatocytes represent a stage in tumor progression during the development of hepatocellular carcinomas. Alkaline phosphatase activity appeared to be a useful positive histochemical marker for nodular proliferative and neoplastic lesions in the mouse. Acquisition of this enzyme activity by hyperplastic and neoplastic cella may reflect derepression of an oncofetal antigen in as much as the enzyme activity increased only transiently in canaliculi of fetal and neonatal hepatocytes.
Increased maximal airway response to methacholine during seasonal allergic rhinitis in nonasthmatic subjects: relationships with airway wall thickness and inflammation
Authors: LP Boulet, H Turcotte, G Carrier, M Boutet, M Laviolette
Journal: European Respiratory Journal (1995)

This study was carried out to determine whether the increase in airway responsiveness induced by natural antigenic exposure in nonasthmatic subjects is associated with an increase in maximal bronchoconstrictor response (MBR), and if these changes could be due to an increase in airway wall thickness from allergen-induced increase in airway inflammation. In 11 nonasthmatic subjects with seasonal allergic rhinitis, a methacholine challenge was obtained monthly, during and out of pollen exposure. Each subject had a high-resolution chest tomography in and out of the pollen season, to determine the relative thickness of the right intermediary bronchus over its total diameter (T/D), as well as inflammatory cell counts, apparent basement membrane thickness as an indication of subepithelial fibrosis and epithelial desquamation in bronchial biopsy specimens. In season, the mean provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in one second (PC20) decreased from 51.5 to 25.8 mg.mL-1, and the maximal post-methacholine fall in forced expiratory volume in one second (delta FEV1,max) or forced vital capacity (delta FVC) and the slope of the dose response curve (DRS) increased compared with out of season: delta FEV1,max 44 +/- 5 vs 25 +/- 5%; delta FVC 34 +/- 5 vs 16 +/- 4%; and slope of DRS 14.1 +/- 2.8 vs 6.9 +/- 1.3%/mg.mL-1. No significant change was observed in T/D ratio. The seasonal change in delta FVC was positively correlated with the delta FEV1,max (rs = 0.891) and the change in DRS (rs = 0.909), but not with the change in PC20, nor with changes in bronchial biopsy inflammatory features or T/D ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Ambient nitrogen dioxide concentrations increase bronchial responsiveness in subjects with mild asthma
Authors: G Bylin, G Hedenstierna, T Lindvall, B Sundin
Journal: European Respiratory Journal (1988)

Twenty subjects with mild asthma were exposed at rest in a body plethysmograph, to NO2 at 0, 260, 510 and 1,000 micrograms.m3, for 30 min on four separate days. Bronchial responsiveness (histamine inhalation test) was measured after each exposure session. Airway resistance (Raw), thoracic gas volume (TGV) and specific airway resistance (sRaw) were measured before, during and after exposure, and the breathing pattern was monitored during the whole session. Bronchial responsiveness increased significantly after 30 min exposure to 510 micrograms.m3 NO2 (p less than 0.01). There were also tendencies to an increased bronchial responsiveness after exposure to 260 and 1,000 micron.m3 NO2, but these changes were not statistically significant. Effects on airway resistance and breathing pattern were not demonstrated by exposure to 0-1,000 micrograms.m3 NO2. We conclude that short-term NO2 exposure at about 500 micrograms.m3 slightly affects human bronchial responsiveness in subjects with mild asthma.