tbuckley/cabot-search huggingface dataset:
District General Hospital experience with indwelling pleural catheters(IPC); in-patient and outpatient management
Authors: Narendra Babu Rampura Chinnappa, Amit Benjamin
Journal: European Respiratory Journal (2014)

Introduction:  IPC9s are effective in controlling recurrent and symptomatic malignant pleural effusions and are recommended (Grade B Evidence) in the current British Thoracic Society Guidelines 1 . Recent Trial data has shown in reduction in Length of stay (LOS.) 2    Aims and Objectives: At our DGH (population 289,400) IPC9s have been used since July 2011. We initially inserted all IPC9s on inpatients (n=12) and as experience was gained the IPC9s were inserted on outpatients from July 2013 (n=6)  To study and review the 1. number of IPC9s inserted as in patients and out patients 2.Cancer types 3.Performance status (PS)4. LOS (in-patients) 5.Estimated days saved by performing procedure as outpatient 6.Complications.   Methods:  Retrospective collection of data from the patients who had IPC9S inserted since July 2011 till Dec 2013.   Results : Results are concluded in the Table (1).   Conclusion:  At our DGH we required 1 year of inpatient experience (n=12) before IPC9s were used with outpatients. Even with just 6 outpatient IPC insertions, 27 hospital days have been saved to date. We conclude from our experience at least a year of inpatient experience with multidisciplinary staff involvement and education is required before OPD management of IPC9s is attempted. Outpatients also need a PS of 0 -2 .OPD management does however seem to result in bed day savings.   References:  1) Thorax 2010;65  2) Davies HE,et al. JAMA 2012.
Virus-Specified Changes in the Sugar-Transport Kinetics of Rat Embryo Cells Infected With Murine Sarcoma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Masakazu Hatanaka, Raymond V. Gilden
Journal: JNCI Journal of the National Cancer Institute (1970)

Rat embryo cells transformed by the Harvey strain of murine sarcoma virus showed alterations in the transport characteristics of glucose and several other sugars. These changes were similar to those previously reported for sarcoma virus-transformed mouse cells. Hamster and human cells infected in similar fashion showed neither transformation nor changes in the kinetics of sugar transport.
The Efficacy and Safety of Subcutaneous Clazakizumab in Patients With Moderate‐to‐Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results From a Multinational, Phase IIb, Randomized, Double‐Blind, Placebo/Active‐Controlled, Dose‐Ranging Study
Authors: Michael E. Weinblatt, Philip Mease, Eduardo Mysler, Tsutomu Takeuchi, Edit Drescher, Alberto Berman, Jun Xing, Moshe Zilberstein, Subhashis Banerjee, Paul Emery
Journal: Arthritis & Rheumatology (2015)

Objective Clazakizumab is a humanized monoclonal antibody that binds to the interleukin‐6 (IL‐6) cytokine. This study was undertaken to evaluate the efficacy and safety of clazakizumab in combination with methotrexate (MTX) or clazakizumab monotherapy versus MTX alone in patients with rheumatoid arthritis (RA) and an inadequate response to MTX. Methods In this multinational, phase IIb, randomized, double‐blind, placebo‐controlled, dose‐ranging study, patients were randomized to receive 1) once‐monthly subcutaneous (SC) clazakizumab at 25, 100, or 200 mg plus MTX, 2) once‐monthly SC clazakizumab at 100 mg or 200 mg as monotherapy, or 3) MTX plus placebo (i.e., MTX alone). Adalimumab (40 mg) plus MTX was included as an active reference. The primary end point was the American College of Rheumatology 20% (ACR20) improvement response rate at week 12. Secondary end points included ACR20, ACR50, and ACR70 response rates as well as protocol‐defined remission rates and Health Assessment Questionnaire disability index scores at weeks 12 and 24. Results In total, 418 patients were randomized, and baseline characteristics were balanced across the treatment groups. Patients receving clazakizumab had significantly greater ACR20 response rates at week 12 compared with patients receiving MTX alone (76.3%, 73.3%, and 60.0% of patients in the clazakizumab 25, 100, and 200 mg plus MTX groups, respectively, and 55.0% and 61.0% of patients in the clazakizumab 100 and 200 mg monotherapy groups, respectively, versus 39.3% of patients receiving MTX alone; P &lt; 0.05 for all comparisons). At week 24, all clazakizumab groups had higher ACR20, ACR50, and ACR70 response rates and higher remission rates compared with MTX alone. Rates of serious adverse events ranged from 8.3% to 13.6% in the clazakizumab treatment groups, compared with 3.3% in the MTX alone group. Changes in laboratory data were consistent with the pharmacologic effects of IL‐6 blockade. Conclusion In patients with RA and an inadequate response to MTX, treatment with clazakizumab in combination with MTX or clazakizumab monotherapy was well tolerated, and patients achieved significant improvements in disease activity, including higher rates of remission, as compared with patients receiving MTX alone.
Cisplatin-induced renal toxicity
Authors: D Sheikh-Hamad, K Timmins, Z Jalali
Journal: Journal of the American Society of Nephrology (1997)

Cisplatin administration is frequently associated with renal insufficiency and tubular dysfunction. In this article, a case of massive cisplatin overdose as a result of an accidental substitution for carboplatin is reported. The patient developed oliguric renal failure, hepatotoxicity, ototoxicity, peripheral neuropathy, blindness, and severe myelosuppression. A therapeutic trial with N-acetylcysteine to reverse renal toxicity was attempted. This article reviews the literature on cisplatin nephrotoxicity, with an emphasis on possible mechanisms involved, and suggests therapy for its modification.
Oxygen Saturation, Pulse Rate, and Particulate Air Pollution
Authors: C. ARDEN III POPE, DOUGLAS W. DOCKERY, RICHARD E. KANNER, G. MARTIN VILLEGAS, JOEL SCHWARTZ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Although epidemiological studies have linked particulate air pollution with cardiopulmonary mortality, underlying biological mechanisms remain largely unknown. Unexplored pathophysiological pathways include transient declines in blood oxygenation and/or changes in cardiac rhythm following particulate exposure. In this study, blood oxygen saturation using pulse oximetry (SpO2) and pulse rate were measured daily on a panel of 90 elderly subjects during the winter of 1995-1996 in Utah Valley. Associations of SpO2 and pulse rate with respirable particulate pollution (particles with an aerodynamic diameter </= a nominal 10 microm [PM10]) were evaluated. SpO2 was not consistently associated with PM10. Pulse rate and the odds of the pulse rate being elevated by 5 or 10 beats per minute (beats/min) were associated with PM10 on the previous 1 to 5 d. A 100 microg/m3 increase in previous-day PM10 was associated with an average increase of 0.8 beats/min and 29 and 95% increased odds of the pulse rate being elevated by 5 or 10 beats/min, respectively. Although there was little evidence of pollution-related hypoxia, alterations in pulse rate could reflect cardiac rhythm changes and may be part of the pathophysiology linking particles to cardiopulmonary mortality. The observed lag structure is consistent with particulate-induced pulmonary inflammation and cytokine release, but the biological relevance requires further study.
Metabolic Effects of Prostatectomy
Authors: P A Hamilton Stewart, I M Barlow
Journal: Journal of the Royal Society of Medicine (1989)

Transurethral resection syndrome (TURS), complicating transurethral resection of the prostate (TURP) has been ascribed to hyponatraemia but reports have indicated that hyperammonaemia following metabolism of glycine can be the main cause. Prospective data has been collected on 96 prostatectomy patients (82 TURP and 14 retropubic). The retropubic group showed no significant postoperative change in the serum sodium or plasma ammonia. Of the TURP group, no TURS occurred although hyponatraemia was noted in 32 patients. The weight of prostate resected, the volume of glycine used, the time taken and the plasma ammonia levels were not significantly different in the normonatraemic or hyponatraemic groups. In severely hyponatraemic patients (13 out of 32 with a 10 mmol/l, or greater, decrease in serum sodium) there was a significant rise (P less than 0.05) in plasma ammonia, 1 or 4 h post TURP, which had decreased by 24 h. There was a highly significant increase in serum glycine level in the hyponatraemic compared with the normonatraemic group (P less than 0.001). There was no correlation between serum glycine and plasma ammonia levels in the normonatraemic or hyponatraemic group. There were nine patients with post TURP plasma ammonia levels greater than 100 mumol/l (mean 254) who experienced no mental confusion: six of these patients were hyponatraemic. The weight of prostate resected (mean 26 g), volume of glycine used (mean 181) and operation time (mean 39 min) were all relatively low. Subsequently, TURS has occurred in a patient, with severe hyponatraemia and hyperglycinaemia but no hyperammonaemia. This study shows that hyperammonaemia does not always correlate with hyponatraemia or hyperglycinaemia, and high plasma ammonia levels can occur in the absence of TURS.
Is parental smoking a risk factor for sleep-disordered breathing in children?
Authors: Afroditi Sakellaropoulou, Katerina Haidopoulou, Maria Emporiadou, Athanasios Kaditis, Maria Hatzistilianou
Journal: European Respiratory Journal (2013)

Passive exposure to cigarette smoking has been associated with snoring and obstructive sleep apnea syndrome (OSAS) in children and snoring-related sleep fragmentation.  The purpose of this study was to examine if parental smoking is a potential risk factor for OSAS in children.  Data was collected from 42 children who were evaluated with polysomnography. The presence and the severity of sleep-disordered breathing were quantified by the frequency of apnoeas and hypopnea per hour of sleep (AHI).  The study group consisted of 42 children (2.5-14.5 years, 64.3% boys). 33.3% children had mild, 38.1% moderate and 28.6% severe OSAS, based on AHI. 26/42 parents were active smokers (61.9%). 18/42 (42.9%) children had a history of wheezing or bronchial asthma. No statistical importance was recorded between parental smoking and symptoms related to upper airways obstruction, as mouth breathing during sleep (p=0.406) and during the day (p=0.546), observed apneas (p=0.77), snoring every night (p=0.19), nose speech (p=0.35) and nasal congestion (p=0.10). Although children with parents who smoke present easier fatigue at home (p=0.014), there wasn’t a correlation with learning difficulties (p=0.29), lack of concentration (p=0.24), sleep latency (p=0.68) or REM latency (p=0.57). Moreover, parental smoking didn’t influence the appearance of bronchial asthma and wheezing (p=0.53), the use of bronchodilators (p=0.75) or inhaled corticosteroids (p=0.527).Exposure to cigarette smoke at home and the presence of asthma didn’t increase the likelihood of habitual snoring or the severity of OSAS. Probably, this result is a dose-response effect between snoring children and the number of cigarettes consumed by their parents.
Effect of Calcium Chromate Dust, Influenza Virus, and 100 R Whole-Body X Radiation on Lung Tumor Incidence in Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: P. Nettesheim, M. G. Hanna, D. G. Doherty, R. F. Newell, A. Hellman
Journal: JNCI Journal of the National Cancer Institute (1971)

Chronic inhalation exposure of C57BL/6 mice to calcium chromate(CaCrO4) dustresultedin a fourfold increasein pulmonary adenoma incidence. Acute exposure to 100 R whole-body X radiation caused a similar increase in tumor incidence. The effects of the two tumorigenic insults were not additive. PRe influenza virus infection suppressed spontaneous as well as X ray- and CaCrO4-induced pulmonary adenoma development. The overall lung adenoma incidence was higher in males than in females. CaCrO4 also induced other pathological changes in the respiratory tract, such as epithelial necrosis and regenerative hyperplasia in the conducting airways, alveolar “bronchiolization,” alveolar proteinosis, and emphysema-like changes, and suppressed the lymphoma incidence.
Evaluation of systemic exposure between two nasal spray formulations of mometasone furoate in healthy subjects
Authors: Mukul Phatak, Siddharth Chachad, Shrinivas Purandare, Geena Malhotra, Kalindi Gandhi
Journal: European Respiratory Journal (2013)

Mometasone furoate (MF) is a topical glucocorticosteroid with local anti-inflammatory properties. This pharmacokinetic study was conducted to evaluate the total systemic exposure of mometasone furoate when administered as nasal spray between the test product (MF aqueous nasal spray suspension 50 mcg/actuation of Cipla Ltd., India) and the reference product (Nasonex, containing MF 50 mcg/actuation of Merck Sharp & Dohme Ltd., UK). In the randomized, open label, crossover study, 48 healthy adult male human subjects received a single dose on two treatment days separated by a washout period of 8 days. The subjects were administered a dose of 400 mcg in each period as 8 puffs (4 puffs in each nostril) under fasting conditions. The plasma samples of 45 subjects completing the study were analyzed and considered for the final pharmacokinetic and statistical evaluations. The 90 % confidence intervals for ratios (%) of the least square mean of the test and reference product of log transformed data for Cmax, AUC0-t and AUC0-inf for MF were 85.61 to 103.17, 96.17 to 115.87 and 94.12 to 112.18 respectively. MF plasma concentration-time profile following administration of the test product was similar to that of the reference product. Hence the two formulations can be concluded to have a similar systemic bioavailability. No serious adverse event was reported during the course of study and both the products were well tolerated after administration of single dose of 400 mcg. In summary, the test product has similar systemic exposure to that of the reference product.
Relation between tumor size, quality of life, and survival in patients with colorectal liver metastases.
Authors: S Earlam, C Glover, C Fordy, D Burke, T G Allen-Mersh
Journal: Journal of Clinical Oncology (1996)

PURPOSE AND METHODS This study assessed the relationship between survival, tumor size, and quality of life (QoL; Rotterdam Symptom Checklist [RSC], Hospital Anxiety and Depression Scale [HAD], and Sickness Impact Profile [SIP]) in 50 patients with colorectal liver metastases (CLM). RESULTS Physical symptom score (RSC) was a stronger survival predictor than tumor size measured on computed tomographic (CT) scan. The best model for predicting survival included QoL questions about diarrhea, eating, restlessness, and ability to work and sleep. The only clinically measured variable included in this best survival prediction model was serum alkaline phosphatase level. This is the first study to show that QoL indices predict survival in CLM. The findings suggest that differences in tumor products and not just in tumor size could influence patient fitness and survival in CLM. Such differences are more accurately estimated by QoL assessment than measurement of tumor size. CONCLUSION QoL provides a better survival estimate than measurement of tumor size and could be used as a surrogate end point for survival in treatment trials.
Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy.
Authors: G Giaccone, M Donadio, G Bonardi, F Testore, A Calciati
Journal: Journal of Clinical Oncology (1988)

Fifty patients with small-cell lung cancer (SCLC) were treated with teniposide (VM26) at 120 to 140 mg/m2 on days 1, 3, and 5, every 3 weeks. Twelve elderly patients were administered VM26 as first-line chemotherapy. Toxicity was manageable, myelosuppression being the major side effect. The response rate for 44 evaluable patients was 34% (36% for untreated patients); the median durations of response and survival were 230 and 208 days, respectively. Effectiveness of prior chemotherapy and time from last administration was found to influence patient response to VM26: 42% of responders to prior chemotherapy responded to VM26, while 0% of the nonresponders to prior chemotherapy responded to the new agent. Moreover, among patients pretreated with chemotherapy, 12% of those recently treated (earlier chemotherapy ending less than or equal to 2.6 months before administration of VM26) responded to VM26, while 53% of patients treated greater than 2.6 months earlier responded to VM26. Survival was influenced by common prognostic factors (performance status, weight loss, prior chemotherapy exposure). Selection of pretreated patients by type of exposure to prior chemotherapy may help in the testing of new drugs in this disease.
The effects of intra-nasally administered anti-inflammatory compounds in a mouse model of acute COPD exacerbations
Authors: Vince Russell, Andrew Connolly, Joanna Dlugozima, Paul Woodman, Alan Young
Journal: European Respiratory Journal (2013)

Exposure to tobacco smoke (TS) for 4d induced a steroid-insensitive lung inflammation in mice which was exaggerated by the addition of the viral mimetic poly IC (pIC). The effects of an inhaled steroid and an inhaled p38 inhibitor on the exaggerated inflammation were examined.

Methods Mice were exposed to air or TS for 4d. Saline or pIC was administered intra-nasally and mice killed 24h after the last exposure, the lungs lavaged and cells counted. Single intra-nasal doses of vehicle, Fluticasone proprionate (FP, 0.3mg/kg) or the p38 inhibitor PF-03715455 (PF-55, 0.1mg/kg) were dosed 2h after the final challenge.

Results TS-exposure caused a significant cellular infiltration into the lung, which was not inhibited by single doses of either PF-55 or FP. In non-TS exposed mice, pIC induced an inflammation which was also not inhibited by either PF-55 or FP. Administration of pIC in addition to TS-exposure induced an exaggerated inflammatory response which was greater than the additive effect of the two stimuli, with large increases in neutrophil numbers in particular (TS ∼0.07 million, PIC ∼0.2 million, TS+PIC ∼0.6 million). The inflammation at 24h after exposure was significantly inhibited by both PF-55 (54%, p<0.0001) and FP (44%, p<0.001), in contrast to the lack of efficacy of either compound in the TS or PIC groups. However, the level of inflammation never fell below the TS-alone baseline.

Conclusions TS exposure for 4d induced a lung inflammation which was insensitive to steroid. Addition of PIC elicited a markedly enhanced inflammatory response that was sensitive to intra-nasal administration of PF-03715455 and also to FP, thus mimicking features of human COPD.
Pulmonary hypertension due to alveolar hypoventilation: Functional impact and improvement of haemodynamics and exercise capacity under non-invasive positive pressure ventilation
Authors: Matthias Held, Johanna Walthelm, Stefan Baron, Christine Roth, Berthold Jany
Journal: European Respiratory Journal (2012)

Background: For pulmonary hypertension (PH) due to lung diseases guidelines recommend treatment of the underlying disease. Due to preserved cardiac index (CI) in alveolar hypoventilation the functional impact of elevated pulmonary artery pressure (PAP) is not clear. The impact of non-invasive positive pressure ventilation (NIPPV) on exercise capacity of patients with PH due to alveolar hypoventilation is unclear.  Objective: To characterize the functional impact of PH due to alveolar hypoventilation and the haemodynamic and functional consequences of NIPPV.  Methods: Analysis of hemodynamics and functional capacity of 18 patients with daytime PH due to alveolar hypoventilation. The analysis included the data from baseline after a complete diagnostic work-up and after 3 months of NIPPV.  Results: Patients presented with a mean PAP (mPAP) of 49 +/- 12 mmHg, a CI (3,21+/- 0,66), a 6-minute walking distance (6-MWD) of 303+/-133 m and severely elevated nt-pro-BNP levels. mPAP correlated negatively with maximal workload (R=-0,71667, p=0,029) and six-minute-walking distance (R=-0,621, p= 0,010).  Under NIPPV, we found a significant reduction of mPAP (-17,75 mmHg, p=0,0005), NT-pro-BNP serum levels (-2110 pg/ml, p= 0,0014), improvement of the 6-MWD (+66 m, p=0,0082) and maximal workload (+18 W, p=0,028). CI did not change significantly. Changes of workload and mPAP correlated negatively (R= -0,7545, p= 0,0305).  Conclusions: Despite preserved CI elevated mPAP has a functional impact for patients with PH due to alveolar hypoventilation. NIPPV leads to a significant reduction of PH and improvement of exercise capacity.
Advanced glycation endproducts and lung function in COPD
Authors: Michelle John, Maath Al Haddad, Sam Hussain, Charlotte Bolton
Journal: European Respiratory Journal (2014)

Advanced glycation endproducts (AGE) are markers of glycaemic and oxidative stress and pro-inflammatory, leading to collagen cross-linking. Skin autofluoresence is a non-invasive measure of skin AGE, validated against skin biopsies, reflecting tissue accumulation.  Hypothesis: Skin AGE is increased in patients with COPD compared to controls and inversely related to lung function.  Caucasian subjects, with and without COPD, were assessed at clinical stability. Post-bronchodilator spirometry and skin AGE were performed and self-reported medical and smoking history recorded.  Consenting patients with COPD, n=172 (62%male) had mean (SD) age: 68(8)yrs and FEV 1 %pred: 59(18)%. Controls, n=88 (60%male), were aged 66(10)yrs and FEV 1 %pred: 100(14)%.  Skin AGE was greater in patients with COPD: 3.0(0.5)AU compared to controls 2.7(0.5)AU, p 1 % in the total group r=-0.28, p  There was no significant difference in skin AGE between those with IHD (n=38) and without but greater in those with diabetes (n=32) compared to those without, p  Skin AGE is increased in patients with COPD compared to controls and independently inversely associated with airways obstruction. It is a simple non-invasive tool to measure glycaemic and oxidative stress and the clinical application in COPD should be investigated further.
Abstract 9888: Is There Additional Prognostic Value of Stress Echocardiography in Patients Achieving a High Exercise Capacity (≥10 Metabolic Equivalents)?
Authors: Siu-Sun Yao, Vikram Agarwal, Farooq A Chaudhry
Journal: Circulation (2011)

Background: High exercise capacity is a predictor of favorable prognosis in patients with known or suspected coronary artery disease. The purpose of this study was to examine the prognostic value of stress echocardiography (SEcho) in patients achieving high exercise workload. Methods: We evaluated 970 patients (51 ± 11 years; 62% male) achieving nine minutes (≥10 metabolic equivalents) on a Bruce protocol by treadmill SEcho. Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal SEcho was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Followup (3.4 ± 1.5 years) for non-fatal myocardial infarction (n = 11) and cardiac death (n = 3) were obtained. Results: By univariate analysis, both peak wall motion score index (p=0.002) and number of new ischemic wall motion abnormalities (p&lt;0.0001) were significant predictors of cardiac events. Cumulative survival in patients achieving nine minutes (≥10 metabolic equivalents) was signficantly worse in patients with abnormal (ischemic) vs. normal (nonischemic) SEcho (1.1%/year vs. 0.2%/year, p=0.001)(Graph). Multivariate logistic regression analysis identified number of new ischemic wall motion abnormalities as the strongest predictor of cardiac events (RR 1.27, 95% CI 1.0-1.6, p=0.01). Conclusions: The ability to achieve nine minutes (≥10 metabolic equivalents) by treadmill stress echocardiography confers a benign prognosis (~1.0%/year). In the setting of high achieved exercise capacity, stress echocardiography (absence or presence of ischemia) is further able to effectively risk stratify a low risk group.