tbuckley/cabot-search huggingface dataset:
Hyponatremia induced by vasopressin or desmopressin in female and male rats.
Authors: J G Verbalis
Journal: Journal of the American Society of Nephrology (1993)

Previous studies have demonstrated that hyponatremia induced by continuous sc infusion of desmopressin (dDAVP) in combination with a liquid diet allows brain volume adaptation with negligible morbidity and mortality in rats. In contrast, some studies of hyponatremia induced by injections of long-acting preparations of arginine vasopressin (AVP) have reported mortality rates as high as 20 to 80%. To evaluate the possibility that the use of AVP to produce antidiuresis may cause greater mortality as a result of increased brain edema, this study examined brain water and electrolyte contents of male and female rats after varying periods of hyponatremia induced by continuous sc infusions of either dDAVP (5 ng/h) or AVP (100 ng/h). Rats infused with AVP had AVP levels in plasma elevated into ranges reported in patients with the syndrome of inappropriate antidiuretic hormone secretion (17.5 +/- 2.0 pg/mL); however, despite the production of comparably severe degrees of hyponatremia with both AVP and dDAVP infusions (105 to 115 mmol/L), no mortality occurred in any of the rats (N = 40 AVP infused and N = 40 dDAVP infused). AVP- and dDAVP-induced hyponatremia both caused transient brain edema in female and male rats, but brain water content returned to the levels of normonatremic controls after 5 days in the females and 10 days in the males. However, at no time during the 10-day study period did brain water content differ significantly between rats infused with AVP or dDAVP, either in females or males. Decreases in brain electrolytes were also equivalent in the AVP- and dDAVP-infused male and female rats.(ABSTRACT TRUNCATED AT 250 WORDS)
A review of the racial differences in the lung function of normal Caucasian, Chinese and Indian subjects
Authors: TS Yang, J Peat, V Keena, P Donnelly, W Unger, A Woolcock
Journal: European Respiratory Journal (1991)

In the clinic, predicted normal values are widely used for routine assessments and, therefore, it is important that the noted differences in lung volumes between the races are recognized. Further epidemiological studies, using comparative methods and standard statistical techniques, are essential in order to quantify apparent differences between the races and to standardize normal values for race, especially with regard to age, with greater accuracy.
Patterns of sedentary behaviour and physical activity following lung resection for non-small cell lung cancer
Authors: Vinicius Cavalheri, Sue Jenkins, Nola Cecins, Martin Phillips, Lucas Sanders, Kylie Hill
Journal: European Respiratory Journal (2014)

Aim:  To compare patterns of sedentary behaviour and physical activity (PA) in people following lung resection for primary non-small cell lung cancer (NSCLC) with healthy controls.   Methods:  Participants between 6 to 10 weeks following lobectomy for primary NSCLC (LC-group) and age and gender-matched healthy controls (HC-group) wore two activity monitors (SenseWear Armband [SWA] and Stepwatch Activity Monitor [SAM]), during waking hours, for 7 consecutive days. Using SWA data, Metabolic Equivalent of Tasks (METs) was taken to measure the proportion of time during waking hours participants spent in sedentary behaviour (l1.5 METs), light (1.5 to 3.0 METs), moderate (3.0 to 6.0 METs) or vigorous intensity PA (g6.0 METs). Daily step count was measured via the SAM.   Results:  Data were available on 18 participants with NSCLC (13 females; age 68 ± 9 yr [mean ± standard deviation]; BMI 25 ± 5 kg·m -2 ) and 17 healthy controls (10 females; age 69 ± 5 yr; BMI 26 ± 4 kg·m -2 ). Daily step count was lower in the LC-group (9,056 ± 3,777) compared with the HC-group (11,455 ± 2,882) (p = 0.04). Compared to the HC-group, the LC-group spent a greater proportion of time in sedentary behavior (69 ± 14% versus 61 ± 13%; p = 0.04) and a smaller proportion of time in light PA (20 ± 9% versus 26 ± 8%; p = 0.03). Time spent in moderate and vigorous PA was similar between the groups (p g 0.05).   Conclusions:  People following lobectomy for NSCLC walk less than their contemporaries. They appear to increase the time spent in sedentary behaviour at the expense of time spent in light intensity PA. These data suggest that interventions aiming to decrease sedentary behaviour in this population are indicated.
Pak1 Phosphorylation of Snail, a Master Regulator of Epithelial-to-Mesenchyme Transition, Modulates Snail's Subcellular Localization and Functions
Authors: Zhibo Yang, Suresh Rayala, Diep Nguyen, Ratna K. Vadlamudi, Shiuan Chen, Rakesh Kumar
Journal: Cancer Research (2005)

Abstract The process of epithelial-mesenchymal transition plays a pivotal role in the conversion of early stage tumors into invasive malignancies, and has been shown to be regulated by the zinc finger phosphoprotein, Snail; however, no upstream signaling kinases have been shown to modulate Snail functions. Since the invasiveness of breast cancer cells is also influenced by p21-activated kinase 1 (Pak1) signaling, we investigated Pak1's potential mechanistic role in the regulation of Snail functions. We found for the first time that Pak1 promotes transcription repression activity of Snail from E-cadherin, occludin, and aromatase promoters. Pak1 regulates the repressor activity of Snail by phosphorylating on Ser246. Pak1 phosphorylation of Snail supports Snail's accumulation in the nucleus as well as its repressor functions. A Ser246Ala substitution in Snail or Pak1 knockdown by short interference RNA blocked Pak1-mediated Snail phosphorylation, leading to increased cytoplasmic accumulation of Snail and attenuation of Snail repressor activity in breast cancer cells. The regulation of phosphorylation and function of Snail by Pak1 represents a novel mechanism by which a signaling kinase might contribute to the process of epithelial-mesenchymal transition.
Electronic screening tool for pneumonia: Performance and utilization
Authors: Barbara Jones, David Collingridge, Al Jephson, Jeffrey Ferraro, Kumar Mynam, Peter Haug, Herman Post, Caroline Vines, Todd Allen, Nathan Dean
Journal: European Respiratory Journal (2012)

RATIONALE:  We developed a real-time electronic screening tool that identifies patients with pneumonia in the emergency department (ED) using the electronic medical record. Our aim was to evaluate performance and compare utilization rates 6 months after tool initiation.  METHODS:  Our screening tool uses Bayesian logic to combine electronically recorded clinical data with a natural language program that identifies evidence of pneumonia within radiographic reports. Once a patient is identified, the ED physician can confirm the diagnosis then proceed with a decision support tool for management recommendations. In 4 EDs located in Salt Lake City, among all patients obtaining a chest radiograph for the periods of May 5-Jul 10 2011, and Oct 1-Dec 31 2011, a random selection of 300 as well as 60 tool-positive patient records was evaluated by three physician authors for clinical and radiographic evidence of pneumonia. Sensitivity and specificity compared to physician review, ED physician acknowledgment, and tool utilization were evaluated.  RESULTS:  13,859 patients had chest imaging done; the rate of pneumonia was 8.2%. Sensitivity was .74, and positive predictive value .51. Among the true- positive cases, ED physicians9 recognition and agreement with the tool alert showed a non-significant increase from 37% (15/41) to 53% (21/40) (p=.22). Of all true pneumonia cases, utilization of the decision support tool increased significantly, from 12% (6/49) to 48% (29/60) (p=.004).  CONCLUSION:  Our electronic screening tool demonstrated moderate sensitivity and positive predictive value compared to physician review. Physician recognition and usage increased over time.
Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities.
Authors: D R Gandara, W A Nahhas, M D Adelson, S M Lichtman, E S Podczaski, S Yanovich, H D Homesley, P Braly, P S Ritch, S R Weisberg
Journal: Journal of Clinical Oncology (1995)

PURPOSE Diethyldithiocarbamate (DDTC) blocks cisplatin-induced toxicities in animal models without inhibiting antitumor effects. DDTC chemoprotection was tested in a randomized, multicenter, double-blind comparison versus placebo (PB) in patients with lung or ovarian cancer. Primary end points were nephrotoxicity, ototoxicity, neuropathy, and completion of therapy. PATIENTS AND METHODS Between April 1990 and February 1992, 221 patients were registered with small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), or ovarian cancer. Cisplatin (100 mg/m2) and cyclophosphamide (in ovarian cancer) or etoposide (in lung cancer) were administered with either DDTC (1.6 g/m2 over 4 hours) or PB intravenously, every 4 weeks for a planned six cycles. RESULTS At an interim safety analysis, data were available for 195 patients from the combined lung and ovarian cancer populations (PB, 99 patients; DDTC, 96 patients). Withdrawal for chemotherapy-induced toxicities occurred in 9% of PB-treated patients and 23% of DDTC-treated patients (P = .008). The mean cisplatin delivered dose-intensity (DDI) was 23 mg/m2/wk on both arms. However, the mean cisplatin cumulative dose delivered (CDD) was 379 mg/m2 on the PB arm, compared with 247 mg/m2 on the DDTC arm (P = .0001). At the time of interim analysis, 28% of PB-treated patients had completed all six cycles of therapy, compared with only 6% of DDTC-treated patients (P &lt; .001). Although, clinical hearing loss, neuropathy, emesis, and myelosuppression were equivalent in the two treatment arms, DDTC-treated patients had more nephrotoxicity as determined by changes in serum creatinine concentration. Toxicities related to DDTC infusion included transient hypertension, flushing, and hyperglycemia. DDTC did not compromise response rates in either tumor type. CONCLUSION This study did not demonstrate a significant chemoprotective effect against cisplatin-induced toxicities with the DDTC dose schedule tested. Patients who received DDTC received lower cumulative doses of cisplatin, but were more likely to be withdrawn from treatment early due to chemotherapy-related toxicities.
Comparison of repetitive extragenic palindromic sequence-based PCR with PCR ribotyping and pulsed-field gel electrophoresis in studying the clonality of Clostridium difficile
Authors: T. Pasanen, S.M. Kotila, J. Horsma, A. Virolainen, J. Jalava, S. Ibrahem, J. Antikainen, S. Mero, E. Tarkka, M. Vaara, P. Tissari
Journal: Clinical Microbiology and Infection (2010)
Pirfenidone post-authorization safety registry (PASSPORT) – Interim analysis of IPF treatment
Authors: Dirk Koschel, Vincent Cottin, Magnus Skold, Sara Tomassetti, Arata Azuma, Christophe Giot, David Yocum, Sundos Hamza, Toby M. Maher
Journal: European Respiratory Journal (2014)

Introduction 

Pirfenidone (Esbriet®) is approved for mild/mod idiopathic pulmonary fibrosis (IPF). PASSPORT is a post-authorization safety registry required by the European Medicine Agency.

Objective 

Present interim data from PASSPORT

Method 

Up to 140 EU sites will enroll 1000 patients. Safety data are recorded at routine clinic visits for 2 years. Adverse drug reactions (ADR: a noxious, unintended drug response at therapeutic doses) and serious ADRs (SADR: ADRs that are life-threatening; cause death, disability, congenital anomaly; require hospitalization or an intervention to prevent permanent impairment) are collected.

Results 

Data from 530 patients enrolled by 68 sites in 7 countries are included. Age was 69 ± 8.8 years (mean ± SD); IPF diagnosis duration (1.8 ± 3.51 years); 81% were men. Median time in study was 5.5 months; total exposure was 284 person-years.

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Of 311 patients with ADRs, 85 discontinued due to ADR and 41 for other reasons. Dosing of patients discontinuing due to ADR compared to those continuing pirfenidone showed a significant association between dose adjustment (reduction or brief interruption) and remaining on therapy. When ADRs were managed by dose adjustment, patients were less likely to discontinue (24.7% vs 75.3%; chi2=5.210, df=1, p=0.02).

Conclusion 

PASSPORT ADRs are comparable to those in clinical trials of pirfenidone in IPF. No new safety issues emerged. Dose adjustment may influence long-term tolerability of pirfenidone.
Assessing the painful, uninflamed eye in primary care
Authors: Lucia Kuffova, John V Forrester, Andrew Dick
Journal: BMJ (2015)

#### The bottom line

Eye pain is common. Around 2-5% of general practice patients have an eye complaint featuring pain in and around the eye (ocular, periocular, and periorbital pain, described here collectively as eye pain).1 Among patients attending an ophthalmic emergency department in New Zealand, more than 50% of new referrals were from general practices,2 with eye pain being the most common symptom. The authors suggested that referrals could be reduced with better initial diagnosis.

Eye pain with an inflamed, red eye is common and can be readily triaged for a management plan, in most cases by simple examination with a direct ophthalmoscope3 or pen torch. This is discussed elsewhere in relation to the differential diagnosis and treatment of conjunctivitis4 and when to refer for slit-lamp examination for sight threatening ocular surface inflammation or uveitis.5 Eye pain in an uninflamed (white) eye is less common.6

Guidelines for the diagnosis of conjunctivitis have been produced by the Dutch College of General Practitioners,7 and evidence based summaries on management of the red eye are available (http://cks.nice.org.uk/red-eye), but no validated guidelines for the painful, inflamed or uninflamed, eye have been developed. The present advice is based on …
Flexible Electronics: Light Weight and Flexible High-Performance Diagnostic Platform (Adv. Healthcare Mater. 10/2015)
Authors: Daniil Karnaushenko, Bergoi Ibarlucea, Sanghun Lee, Gungun Lin, Larysa Baraban, Sebastian Pregl, Michael Melzer, Denys Makarov, Walter M. Weber, Thomas Mikolajick, Oliver G. Schmidt, Gianaurelio Cuniberti
Journal: Advanced Healthcare Materials (2015)

A flexible light weight diagnostic platform is realized on cost-efficient large-area flexible foils enabling its cost-efficient high-volume delivery to medical institutions worldwide. The devices presented by L. Baraban, D. Makarov, and team on page 1517 allow the timely diagnosis of viral or infectious diseases, for example, the here demonstrated H1N1 subtype of the Avian Influenza Virus.
Atorvastatin in Pulmonary Arterial Hypertension (APATH) study
Authors: Wei-Jie Zeng, Chang-Ming Xiong, Lan Zhao, Guang-Liang Shan, Zhi-Hong Liu, Fang Xue, Qing Gu, Xin-Hai Ni, Zhi-Hui Zhao, Xian-Sheng Cheng, Martin R. Wilkins, Jian-Guo He
Journal: European Respiratory Journal (2012)

Statins have been shown to both prevent and attenuate pulmonary hypertension in animal models. This study investigates the potential therapeutic benefits of atorvastatin as an affordable treatment for pulmonary hypertension patients. 220 patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were randomised, double-blind, to receive atrovastatin 10 mg daily or matching placebo in addition to supportive care. At 6 months, 6-min walk distance decreased by 16.6 m in the atorvastatin group and 14.1 m in the placebo group. The mean placebo-corrected treatment effect was -2.5 m (95% CI: -38–33; p=0.96), based on intention to treat. A small nonsignificant increase in pulmonary vascular resistance and fall in cardiac output was seen in both treatment groups. There was no significant difference in the proportion of patients who improved, remained stable or showed a deterioration in World Health Organization functional class between atorvastatin and placebo treatments. Nine patients died in the atorvastatin group and 11 in the placebo group. Serum cholesterol levels fell significantly on atorvastatin treatment. Discontinuation rates were 23.2% and 26.9% on atorvastatin and placebo, respectively. Atorvastatin 10 mg daily has no beneficial effect on the natural history of PAH or CTEPH over 6 months.
Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review.
Authors: J C Byrd, W J Edenfield, D J Shields, N A Dawson
Journal: Journal of Clinical Oncology (1995)

PURPOSE To discuss the predisposing risk factor for all forms of extramedullary leukemia (EML) and to review the clinical features, prognostic significance, and treatment strategies for primary EML and leukemia cutis (LC)/granulocytic sarcomas (GS) in the setting of acute nonlymphocytic leukemia (ANLL). METHODS A review of all reports published since 1965 related to all forms of extramedullary leukemia (LC, GS, gingival hypertrophy, and meningeal leukemia [ML]). RESULTS Several factors, including chromosomal abnormalities [t(8;21), inv(16)], cell-surface markers (CD56, CD2, CD4, CD7), French-American-British (FAB) subtype (M2, M4, M5), blast differentiation and maturation, patient nutritional status, age, cellular immune dysfunction, high presenting leukocyte count, and decreased blast Auer rods, have been associated with a higher incidence of EML. Of 154 published cases of primary EML identified, 71 (46%) were initially misdiagnosed. The addition of immunohistochemical stains can assist in preventing such misdiagnoses and should be included in all atypical lymphoma/carcinoma cases. Only one of the patients (3%) with primary EML did not progress to ANLL in the absence of chemotherapy. In contrast, 66% of patients who received chemotherapy for the primary EML never developed ANLL. The prognostic significance of EML at presentation and medullary relapse of ANLL is uncertain. Isolated extramedullary recurrence of ANLL always heralds bone marrow relapse and should be treated with reinduction chemotherapy. Close clinical follow-up observation is necessary to insure resolution of EML. Radiation therapy is an effective local treatment for resistant or symptomatic EML. CONCLUSION Many advances in diagnoses and treatment of EML have been made. Future investigations are needed to define the clinical significance of EML in patients with ANLL treated with modern chemotherapy or bone marrow transplantation.
The value of immunohistochemical markers in the differential diagnosis of adenocarcinomas
Authors: Aysegul Eylen, Aysegul Karalezli, Olcay Kandemir, Gokhan Aykun, Hatice Hasanoglu
Journal: European Respiratory Journal (2011)

When differential diagnosis of adenocarcinoma in lung cannot be made, immunohistochemical staining may be necessary. Value of immunohistochemical staining in the differential diagnosis of adenocarcinomas was evaluated.  74 cases of different adenocarcinomas were enrolled. Pathology slides were stained with routine H&E staining and immunohistochemical markers. Positive CK7 immunostaining was seen in 100% of lung adenocarcinomas, papillary thyroid adenocarcinomas (PTC) and breast invasive ductal carcinomas (BIDC) and 15% of gastrointestinal (GI) adenocarcinomas, whereas none of prostate adenocarcinomas were positive. Positive CK20 immunostaining was seen in 75% of GI carcinomas and 10% of prostate adenocarcinomas whereas none of lung adenocarcinomas, BIDCs and PTCs showed positive CK20 immunostaining. TTF-1 staining was observed in 100% of PTCs, 83.3% of lung adenocarcinomas, 20% of BIDCs, 15% of GI carcinomas and 10% of prostate carcinomas. Positive p53 immunostaining was seen in 87.5% of lung adenocarcinomas, 85% of GI adenocarcinomas, 90% of PTCs and 80% of BIDCs. P53 staining wasn9t observed in prostate adenocarcinomas. CK7+CK20- staining panel9s sensitivity and specificity was found as 100% and 90% respectively in differential diagnosis of lung and GI adenocarcinoma. In differential diagnosis of lung adenocarcinomas from breast adenocarcinomas, TTF-1 marker had 83.3% sensitivity and 80% specificity.  Consequently, immunohistochemical studies were found valuable in differential diagnosis of lung adenocarcinomas from other adenocarcinomas. Especially in patients with lung adenocarcinoma CK 7+CK20- staining pattern seem to give important contribution to differential diagnosis.
Frequency and impact on prognosis of signs of pulmonary veno-occlusive disease on high resolution computed tomography in patients with scleroderma associated pulmonary arterial hypertension
Authors: Sven Günther, Sophie Maitre, Alice Berezne, Xavier Jaïs, Andrei Seferian, Olivier Sitbon, Gerald Simonneau, Luc Mouthon, Marc Humbert, David Montani
Journal: European Respiratory Journal (2011)

Introduction:  Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary arterial hypertension (PAH) characterised by a progressive obstruction of small pulmonary veins. PVOD has been frequently reported in patients with scleroderma related PAH (SSc-PAH). High resolution chest computed tomography (HRCT) is a non-invasive diagnostic tool used to screen for PVOD. However, no data are available in SSc-PAH patients.   Aims:  To evaluate the frequency and the impact on prognosis of signs of PVOD on HRCT in SSc-PAH.   Methods:  We reviewed HRCT data in 34 consecutive SSc-PAH patients and 30 systemic sclerosis (SSc) patients.   Results:  Lymph nodes enlargement (57.7% vs 3.6%), centrilobular ground-glass opacities (46.2% vs 10.7%) and septal lines (73.1% vs 7.1%) were significantly more frequent in SSc-PAH patients as compared to SSc patients (all P   Conclusion:  Signs of PVOD are frequent on HRCT in patients with SSc-PAH compared to SSc patients without PAH. These signs allow clinicians to detect PVOD in SSC-PAH patients. Survival in affected patients is poor.
Vinorelbine and Paclitaxel as First-Line Chemotherapy in Metastatic Breast Cancer
Authors: L. Romero Acuña, M. Langhi, J. Pérez, J. Romero Acuña, M. Machiavelli, J. Lacava, C. Vallejo, A. Romero, H. Fasce, E. Ortiz, S. Grasso, S. Amato, R. Rodríguez, M. Barbieri, B. Leone
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m 2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m 2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.