tbuckley/cabot-search huggingface dataset:
Multicenter, Phase II Trial of Exemestane as Third-Line Hormonal Therapy of Postmenopausal Women With Metastatic Breast Cancer
Authors: S. Jones, C. Vogel, A. Arkhipov, L. Fehrenbacher, P. Eisenberg, B. Cooper, S. Honig, A. Polli, F. Whaley, E. di Salle, J. Tiffany, A. Consonni, L. Miller
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia &amp; Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] ≥ 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD ≥ 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E 1 ), estradiol (E 2 ), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E 1 and E 2 levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.
Adequate physical activity in students with and without asthma
Authors: Eirini Grammatopoulou, Emmanouil Skordilis, Afroditi Evangelodimou, Solon Karapanagiotis, Michalis Spanos, Aikaterini Haniotou, Konstantinos Bartziokas, Nektarios Stavrou
Journal: European Respiratory Journal (2012)

Background  Early youth is decisive for the adoption of opinions concerning the physical activity which contributes to the decrease of death risk due to chronic diseases.  Aim  To examine differences in physical activities in young students with and without asthma.  Method  578 Physical therapy students in Athens, Greece, aged 18-30 (± 2.07) participated in the study. Adequate physical activity was assessed according the guidelines of the American Cardiology Association and the American College of Sports Medicine (yes-no). Differences in physical activity between students with and without asthma were examined through χ2.  Results  Only the 4.3% of the total sample reported diagnosed asthma. Adequate physical activity was stated by 40% of students with asthma and by 55.3 % of students without asthma. No significant differences were found in physical activity between the two groups (p = .132). Students with asthma didn9t differ in physical activity regarding gender, BMI, sleep duration, alcohol consumption, income, and health-belief (p > .05), while they differed as for smoking (p = .018). Students without asthma didn9t differ (p > .05) in physical activity with regard to BMI, sleep duration, alcohol consumption smoking, income, and their health-belief, while they revealed differences as for sex (p   Conclusion  The results of the present study in one hand are encouraging because students with asthma were as active as those without asthma, but in the other hand they are disappointing because both groups didn9t met American guidelines for the adequate physical activity that have shown to contribute to chronic illnesses prevention.
Seizure Induction by Alcohol in Patients with Epilepsy Experience in two Hospital Clinics
Authors: J Heckmatt, A A Shaikh, M Swash, D F Scott
Journal: Journal of the Royal Society of Medicine (1990)

We surveyed 70 epileptic patients attending a general neurology clinic and 64 patients attending an epilepsy clinic to determine the incidence of alcohol-related seizures. Seven (10%) of the neurology clinic patients and 9 (15%) of the epilepsy clinic patients reported exacerbation of their seizures with alcohol. In the first group, two had been heavy drinkers when under-age, two had features of alcohol dependence, and three had experienced resolution of seizures following cessation of their drinking. In the second group, five drank 4 units/day or more, and one drank more heavily. The importance of alcohol in the causation of these patients' seizures had not previously been appreciated. The relationship of alcoholism to epilepsy has been recognized for many years, but the role of alcohol in the exacerbation of primary epilepsy, and in triggering seizures in epileptic patients is often not recognized. Control of alcohol ingestion is an important factor in the management of epilepsy.
A Genome-Wide Scan Identifies Variants in <i>NFIB</i> Associated with Metastasis in Patients with Osteosarcoma
Authors: Lisa Mirabello, Roelof Koster, Branden S. Moriarity, Logan G. Spector, Paul S. Meltzer, Joy Gary, Mitchell J. Machiela, Nathan Pankratz, Orestis A. Panagiotou, David Largaespada, Zhaoming Wang, Julie M. Gastier-Foster, Richard Gorlick, Chand Khanna, Silvia Regina Caminada de Toledo, Antonio S. Petrilli, Ana Patiño-Garcia, Luis Sierrasesúmaga, Fernando Lecanda, Irene L. Andrulis, Jay S. Wunder, Nalan Gokgoz, Massimo Serra, Claudia Hattinger, Piero Picci, Katia Scotlandi, Adrienne M. Flanagan, Roberto Tirabosco, Maria Fernanda Amary, Dina Halai, Mandy L. Ballinger, David M. Thomas, Sean Davis, Donald A. Barkauskas, Neyssa Marina, Lee Helman, George M. Otto, Kelsie L. Becklin, Natalie K. Wolf, Madison T. Weg, Margaret Tucker, Sholom Wacholder, Joseph F. Fraumeni, Neil E. Caporaso, Joseph F. Boland, Belynda D. Hicks, Aurelie Vogt, Laurie Burdett, Meredith Yeager, Robert N. Hoover, Stephen J. Chanock, Sharon A. Savage
Journal: Cancer Discovery (2015)

Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 × 10(-9); OR, 2.43; 95% confidence interval, 1.83-3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene.Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the NFIB locus as associated with metastatic potential in osteosarcoma.
Renal Function and Intensive Lowering of Blood Pressure in Hypertensive Participants of the Hypertension Optimal Treatment (HOT) Study
Authors: LUIS M. RUILOPE, ANTONIO SALVETTI, KENNETH JAMERSON, LENNART HANSSON, INGRID WARNOLD, HANS WEDEL, ALBERTO ZANCHETTI
Journal: Journal of the American Society of Nephrology (2001)

Abstract. This article reports further analyses of the Hypertension Optimal Treatment (HOT) Study data with the aim to describe ( 1 ) the value of baseline serum creatinine and its clearance (estimated by Cockroft and Gault formula) as predictors of cardiovascular events, ( 2 ) the effects of intensive lowering of BP on cardiovascular events and renal function in patients with reduced renal function, and ( 3 ) the effects on cardiovascular events of adding acetylsalicylic acid to antihypertensive therapy in patients with reduced renal function. The results show that ( 1 ) baseline elevation in serum creatinine and a reduction in estimated creatinine clearance are powerful predictors of cardiovascular events and death. ( 2 ) Reduced renal function at baseline did not preclude the desired control of BP. In contrast to patients with normal renal function, the incidence of major cardiovascular events did not differ in the three groups of patients with mild renal insufficiency randomized to different diastolic BP targets. No significant changes in serum creatinine were seen at the end of the 3.8-yr treatment period in the great majority of patients. However, there was a small group of patients (0.58% of the total study population) whose renal function deteriorated (increase ≥30% over baseline and final serum creatinine concentration ≥2 mg/dl) despite satisfactory reduction of diastolic BP. ( 3 ) The results of this reanalysis of the HOT Study suggest though do not prove that the association of acetylsalicylic acid with intensive antihypertensive therapy offers additional benefit in hypertensive patients with reduced renal function.
Prevalence of co-morbidities with chronic obstructive pulmonary disease (COPD) in a primary care cohort
Authors: Mukesh Singh
Journal: European Respiratory Journal (2014)

Background : Patients with COPD frequently have co-morbidities which impact upon a holistic approach to patient management, prognosis and quality of life.

Objectives : The aim of this retrospective study was to evaluate the prevalence of co-morbidities in COPD patients within a single primary care cohort.

Methods : The clinical record system was searched to identify all registered patients with COPD using ICD-10 coding. Extracted data included date of COPD diagnosis, recorded co-morbidities (obesity, cardiovascular diseases, diabetes mellitus (DM), anxiety/depression and other long term chronic conditions),FEV1,smoking status and body mass index(BMI)

Results : Our records identified 194 patients;113(58.2%) male, 81(41.8%) female, mean age 71 years (41–93). Of this cohort, 25.3% were current smokers, 62.9% ex-smokers, and 11.9% had never smoked. Mean duration since COPD diagnosis was 10.1 years. Based upon NICE 2010 severity criteria, 11.3% patients had mild, 66.5% moderate, 17% severe, and 2.1% had very severe COPD. Average BMI was 28.7±6.5 kg/m² (16.5–55.6). 95% of patients had at least one co-morbidity and 22% had ≥3. Arthritis chiefly osteoarthritis was present in 53.6% of patients. Ischaemic heart disease was seen in 31 patients (16%) who included 26 patients (13.4%) with a history of myocardial infarction, 20 patients (10.3%) with a history of cerebrovascular accident and 11 patients (5.7%) with peripheral vascular disease. A total of 48 patients (24.7%) had co-existent type2 DM of whom 52% were obese.

Conclusions : This study shows that most COPD patients have one or more co-existent co-morbidities which may impact upon quality of life and response to COPD therapy.
Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up
Authors: Robert V Bryant, Daniel C Burger, Joseph Delo, Alissa J Walsh, Sally Thomas, Axel von Herbay, Otto C Buchel, Lydia White, Oliver Brain, Satish Keshav, Bryan F Warren, Simon P L Travis
Journal: Gut (2015)

<h3>Background</h3> Endoscopic mucosal healing is an established treatment target for UC, yet the value of achieving histological remission remains unclear. <h3>Aims</h3> To evaluate histological remission compared to endoscopic mucosal healing for predicting patient outcomes in UC. <h3>Methods</h3> Blinded assessment of endoscopic and histological measures of disease activity was performed on patients with established UC at baseline. Concordance and prognostic values of endoscopic mucosal healing (defined by Baron score ≤1) and histological remission (defined by Truelove and Richards' index) for predicting outcomes of corticosteroid use, hospitalisation and colectomy were determined over a median 6 years follow-up, including κ statistics and Cox regression multivariate analysis. <h3>Results</h3> 91 patients with UC were followed up for a median 72 months (IQR 54–75 months). Overall, concordance between endoscopic and histological remission was moderate (κ=0.56, 95% CI 0.36 to 0.77); 24% patients had persistent inflammation despite endoscopic remission. Histological remission predicted corticosteroid use and acute severe colitis requiring hospitalisation over the follow-up period (HR 0.42 (0.2 to 0.9), p=0.02; HR 0.21 (0.1 to 0.7), p=0.02; respectively), whereas endoscopic mucosal healing did not (HR 0.86, 95% CI 0.5 to 1.7, p0.65; HR 0.83 95% CI 0.3 to 2.4, p0.74; respectively). <h3>Conclusions</h3> Histological remission is a target distinct from endoscopic mucosal healing in UC and better predicts lower rates of corticosteroid use and acute severe colitis requiring hospitalisation, over a median of 6 years of follow-up. Our findings support the inclusion of histological indices in both UC clinical trials and practice, towards a target of 'complete remission'.
Cap‐Dependent Translation Initiation Factor e<scp>IF4E</scp>: An Emerging Anticancer Drug Target
Authors: Yan Jia, Vitaly Polunovsky, Peter B. Bitterman, Carston R. Wagner
Journal: Medicinal Research Reviews (2012)

Abstract Cancer cells tend to be more highly dependent on cap‐dependent translation than normal tissues. Thus, proteins involved in the initiation of cap‐dependent translation have emerged as potential anti‐cancer drug targets. Cap‐dependent translation is initiated by the binding of the factor eIF4E to the cap domain of mRNA. Detailed x‐ray crystal and NMR structures are available for eIF4E in association with cap‐analogs, as well as domains of other initiation factors. This review will summarize efforts to design potential antagonist of eIF4E that could be used as new pharmacological tools and anti‐cancer agents and. Insights drawn from these studies should aid in the design of future inhibitors of eIF4E dependent translation initiation. © 2012 Wiley Periodicals, Inc. Med Res Rev., 32, No. 4, 786‐814, 2012
Withdrawal of Chronic Systemic Corticosteroids in Patients with COPD
Authors: KATHRYN L. RICE, JEFFREY B. RUBINS, FRAN LEBAHN, CONNIE M. PARENTI, PETER G. DUANE, MICHAEL KUSKOWSKI, ANNE M. JOSEPH, DENNIS E. NIEWOEHNER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The benefits of chronic systemic corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are not well established. To determine whether chronic corticosteroid treatment can be safely withdrawn in "steroid-dependent" COPD patients, we performed a double-blind, placebo-controlled study of 38 patients with steroid-dependent COPD. Patients were randomly assigned to receive their usual maintenance prednisone dose for 6 mo (continuous group) or to be withdrawn from prednisone at a rate of 5 mg per week (demand group). The number of COPD exacerbations per patient (primary outcome) was 2.5 ± 2.7 (mean ± SD) in the continuous group and 2.7 ± 2.5 in the demand group (p = 0.60, 95% confidence interval for the difference: − 1.1 to 1.7). Spirometric results, dyspnea, and health-related quality of life did not differ significantly in the two groups. The average daily corticosteroid dose was 10.7 ± 5.2 mg in the continuous group and 6.3 ± 6.4 mg in the demand group (p = 0.003). Weight decreased in the demand group by 4.8 ± 2.0 kg, compared with an increase in the continuous group of 0.5 ± 3.5 kg (p = 0.007). Discontinuation of chronic systemic corticosteroid treatment in steroid-dependent COPD patients did not cause a significant increase in COPD exacerbations, but did reduce total systemic corticosteroid use and body weight. Larger studies may be warranted to establish the relative risks and benefits of chronic corticosteroid treatment of patients with COPD.
Mukoregulatory drugs in treating COPD
Authors: Ardak Zhumagalyieva, Ludmila Karazhanova
Journal: European Respiratory Journal (2014)

Introduction: Acute COPD exacerbations (AECOPD) represent an important cause of morbidity and mortality. Early and effective interventions may improve their outcome and patients' health status.

Objective: This study evaluated the effect of ambrobene retard, on airflow limitation and symptom recovery at AECOPD

Methods: 17COPD patients hospitalized for an acute exacerbation randomly received ambrobene retard 75 mg / day (A) or placebo (P) for 10 days in combination with standard steroid, antibiotic and bronchodilator treatment. Pulmonary function test including spirometry (FVC, FEV1, FEF25–75) and breathlessness, cough, and sputum scale (BCSS) were measured at hospital admission, and 30 days post-exacerbation.

Results: The improvement of lung function parameters and symptom scores from baseline was significantly greater in patients receiving ambrobene retard. Symptom score recovery significantly correlated to improvement of airway obstruction at time 30 in the ambrobene retard group.

Conclusions: Treatment with ambrobene retard plus standard therapy in AECOPD proved to be effective in improving both clinical symptoms, and large and small airway impairment

View this table:

Effect of ambrobene retard on airflow obstruction and symptom recovery in severe COPD exacerbations





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Four and six parameter models of forced random noise respiratory impedance in normals
Authors: H Lorino, C Mariette, AM Lorino, A Harf
Journal: European Respiratory Journal (1989)

Total respiratory impedance has been measured between 3-42 Hz by the forced random noise technique, in 15 subjects breathing either air or a helium oxygen mixture in three experimental conditions: at basal state, and then with a resistor or a tube added at the mouth. Impedance is modelled, either by a 4-parameter model (M4), derived from the series model (resistance, inertance, compliance) by making resistance a linear function of frequency; or by a 6-parameter model (M6) including a central compartment (airway resistance and gas inertance), and a tissue compartment (resistance, inertance and compliance in series) placed in parallel with alveolar gas compliance. The additive resistance is perfectly evaluated by both models, whereas the additive inertance is not accurately estimated by the model M6, the fitting of which combines the real and imaginary parts of impedance. Resistance extrapolated at zero frequency on the one hand, inertance of M4 and central inertance of M6 of the other, are highly correlated. However, changes in some parameters of both models according to the experimental conditions are difficult to explain on physiological grounds. We conclude that the model M6 cannot be easily and accurately identified over such a limited frequency range, at least in normals, while the model M4 yields a simplified description of impedance which may be sufficient for diagnostic purposes.
Approach to the pneumomediastinum with massive subcutaneous emphysema
Authors: Serkan Ozbay, Serife Tuba Liman, Salih Topcu, Asli Gul Akgul, Aykut Elicora, Seymur Salih Mehmetoglu, Huseyin Fatih Sezer
Journal: European Respiratory Journal (2014)

The most common reasons of pneumomediastinum are thoracic trauma, endoscoping procedures, endotracheal entubation and spontaneous pneumomediastinum. The choice of treatment depends on the ethiology, clinical symptoms and the complication risk; and hence varies from spontaneous pneumomediastinum(SPM). Conservative treatment is usually sufficient, but occasionally cervical mediastinotomy or thoracotomy may be necessary.

In the last ten years we treated 15 patients with massive subcutaneous emphysema in our clinic. The mean age for the 10 men and 5 women was 40(12-71). The ethiological factors were blunt thoracic trauma (7 cases), endotracheal entubation (4 cases), after asthma attack( 2 case) and spontaneous pneumomediastinum in 2 cases.. The reasons of traumatic cases (blunt thoracic trauma cases) were traffic accidents (4 cases), direct impact by a blunt heavy object (1 case), compression of the chest in anterior posterior direction (2 case) and falling from height (1 case). Pneumothorax was determined in 3 patients with blunt thoracic trauma. Tube thoracostomy was performed to the patients with pneumothorax. Cervical mediastinotomy was performed to our cases with massive mediastinal emphysema for decompression. The patients were discharged within 4-15 days.

If symptoms of compression are present, conservative treatment shall be avoided and procedures for decompression should be performed(cutaneous and subcutaneous incisions, needle aspiration, mediastinal catheter application and cervical mediastinotomy). The cervical mediastinotomy is the most effective and reliable method of treatment.
The primitive bronchogenic carcinoma in the elderly
Authors: Hanane Benjelloun, Nahid Zaghba, Najiba Yassine, Abdelaziz Bakhatar, Abdelkrim Bahlaoui
Journal: European Respiratory Journal (2012)

The increased incidence of lung cancer in the elderly is associated to the increase of the intrinsic risk to develop a cancer with age, to the ageing of the population and especially to the smoking and the exposure to occupational and environmental carcinogens. We realized a retrospective study of 108 patients aged of 65 year old and older, hospitalized in the department of Respiratory Diseases, UHC Ibn Rochd between January 2008 and January 2010. It is about 96 men and 12 women. The average age is 69 years old. Smoking is found in 90 cases, the symptomatology is dominated by coughing, chest pain, dyspnea in 80 cases, and hemoptysis in 46 cases. The thoracic imaging showed, more the tumoral processus of mediastinal adenopathies in 50 cases, a bone lysis in 12 cases, a balloon release in 10 cases, interstitial syndrome in 8 cases and pleurisy in 7 cases. The bronchoscopy revealed a budding tumor in 56 cases, a tumor infiltration in 24 cases. The diagnosis is based on bronchial biopsies in 68 cases, the transmural needle biopsy in 26 cases, the peripheral ganglial biopsy in four cases, pleural needle biopsy in 6 cases and the thoracotomy in 5 cases. The epidermoid carcinoma is the most common histological type in 45 cases, followed by adenocarcinoma in 40 cases, small cells carcinoma in 10 cases and undifferentiated carcinoma in 13 cases. At the end of the complete physical examination, 55% of the patients were classified stage IV. The bronchogenic carcinoma of the elderly is often revealed in the late stages. Its therapeutic management depends on the patient9s general condition and related defects.