tbuckley/cabot-search huggingface dataset:
ATP Release Mechanisms in Primary Cultures of Epithelia Derived from the Cysts of Polycystic Kidneys
Authors: PATRICIA D. WILSON, JEFFREY S. HOVATER, CASH C. CASEY, JAMES A. FORTENBERRY, ERIK M. SCHWIEBERT
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Autosomal dominant polycystic kidney disease (ADPKD) cyst enlargement is exacerbated by accumulation of fluid within the lumen of the cyst. Extracellular nucleotides and nucleosides stimulate fluid and chloride (Cl - ) secretion across epithelia and are potent autocrine and paracrine agonists within tissues. This study tests the hypothesis that ATP may be released by ADPKD epithelial cells. Once released, extracellular nucleotides and their metabolites may become “trapped” in the cyst lumen. As a consequence, extracellular ATP may augment ADPKD cyst enlargement through stimulation of salt and water secretion across ADPKD epithelia that encapsulate ADPKD cysts. To test this hypothesis, bioluminescence detection assays of ATP released from primary cultures of human ADPKD epithelial cells were compared with non-ADPKD human epithelial primary cultures. ADPKD cultures release comparable or greater amounts of ATP than non-ADPKD cultures derived from proximal tubule or cortex. ATP release in both ADPKD and non-ADPKD primary epithelial monolayers was directed largely into the apical medium; however, basolateral-directed ATP release under basal and stimulated conditions was also observed. Hypotonicity potentiated ATP release into the apical and basolateral medium in a reversible manner. Reconstitution of isotonic conditions with specific osmoles or inhibition with mechanosensitive ion channel blockers dampened hypotonicity-induced ATP release. “Flashfrozen” cyst fluids from ADPKD cysts, harvested from multiple donor kidneys, were screened by luminometry. A subset of cyst fluids contained as much as 0.5 to 10 μM ATP, doses sufficient to stimulate purinergic receptors. Taken together, these results show that ADPKD and non-ADPKD human epithelial primary cultures release ATP under basal and stimulated conditions and that ATP is released in vitro and into the cyst fluid by cystic epithelial cells in concentrations sufficient to stimulate ATP receptors. It is hypothesized that extracellular nucleotide release and signaling may contribute detrimentally to the gradual expansion of cyst fluid volume that is a hallmark of ADPKD.
T-cell prolymphocytic leukaemia: Does the expression of CD8+ phenotype justify the identification of a new subtype?
Authors: S. Ascani, P. Leoni, G.Fraternali Orcioni, I. Bearzi, M. Piccioli, M. Materazzi, P.L. Zinzani, F. Gherlinzoni, B. Falini, S.A. Pileri
Journal: Annals of Oncology (1999)
Panic disorder history in the families of patients with angiographically normal coronary arteries
Authors: M G Kushner, A M Thomas, K M Bartels, B D Beitman
Journal: American Journal of Psychiatry (1992)

The authors evaluated the diagnostic validity of an interview-based panic disorder diagnosis in cardiology chest pain patients with angiographically normal coronary arteries.Patient probands with normal coronary arteries (N = 65) were first contracted immediately after their normal angiogram and were given a structured diagnostic interview. On the basis of the results of the interview, probands were grouped as having panic disorder (N = 19), panic attacks that did not meet frequency criteria for panic disorder (N = 17), or no panic (N = 29). At a later time, patient probands were recontacted and given a structured family history interview that inquired about psychopathology in their first-degree biological relatives (N = 544).As predicted, panic disorder was significantly more prevalent among the first-degree relatives of probands with normal coronary arteries diagnosed with panic disorder or panic attacks than among the family members of probands with normal coronary arteries without panic (17.4% versus 15.7% versus 4.0%). Family members of probands with panic attacks were significantly more likely to be diagnosed with major depression than were the family members of probands with no panic; however, differences did not reach significance for family members of the panic disorder proband group. Groups did not differ significantly in familial alcoholism.These data support the construct validity of an interview-based panic disorder diagnosis among patients with chest pain and normal coronary arteries and suggest that these patients could benefit from treatment for panic disorder.
Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis
Authors: Catherine Gorst, Chun Shing Kwok, Saadia Aslam, Iain Buchan, Evangelos Kontopantelis, Phyo K. Myint, Grant Heatlie, Yoon Loke, Martin K. Rutter, Mamas A. Mamas
Journal: Diabetes Care (2015)

OBJECTIVE Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Medline and Embase were searched (2004–2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type. RESULTS Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08–2.25], two studies), cardiovascular events (1.98 [1.39–2.82]), and retinopathy (2.11 [1.54–2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15–1.57], two studies), macrovascular events (1.21 [1.06–1.38]), ulceration/gangrene (1.50 [1.06–2.12]), cardiovascular disease (1.27 [1.15–1.40]), and mortality (1.34 [1.18–1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability. CONCLUSIONS HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.
The use of telemedicine to care for cancer patients at remote sites
Authors: M. Taylor, K. Khoo, D. Saltman, E. Bouttell, M. Porter
Journal: Journal of Clinical Oncology (2007)

6538 Background: At the BC Cancer Agency -CSI we are challenged to provide systemic cancer care to a population of 720,000 widely dispersed over 250,000 square kilometers. Video-link technology (VT) has been used at our centre since April 2004 to help provide distant care and prevent patient and physician travel. Methods: Patients gave consent for the use of VT. We prospectively collected data on patient and physician experiences as part of on-going quality assurance. We retrospectively collected the clinical data on these patients. Results: We performed 104 encounters on 100 patients between April 2, 2004 and October 4, 2006. Patient characteristics: female 62%, male 38%, average age was 66 years with a range of 28 –83. Extent of cancer was 67% curable, 31% advanced and 7% unknown. Visit type and cancer sites are shown below. Patients rated this experience very highly and the vast majority would repeat the experience rather than travel or wait several weeks to see the doctor in person. Physicians were not as satisfied as the patients; and both groups expressed a concern about the need for physical exam. In those having a consult, 54% had an exam within 60 days, and in none of these patients were the treatment recommendations changed. The majority (57%) of those consult patients that didn’t have an exam had either Stage 0 or I breast cancer or Stage II or III colorectal cancer; and it seems unlikely that physical exam would have changed management in these patients. Conclusions: We were able to deliver cancer care at distant sites with VT and patients found the experience very acceptable. There may not be a need for repeat physical exam in these patients, who had previously been examined by other physicians, prior to referral. No significant financial relationships to disclose. [Table: see text]
Breakthrough Pain (BTP) in Opioid-Tolerant Cancer Patients: A Pan-European Open-Label Multicentre Study with Fentanyl Buccal Tablet (FBT)
Authors: S. Mercadante, A. Davies, J. Jarosz, U.R. Kleeberg, T. O'Brien, P. Poulain, H. Schneid
Journal: Annals of Oncology (2012)
Lymphocyte abnormality associated with HLA-B8 in healthy young adults.
Authors: C C McCombs, J P Michalski
Journal: The Journal of Experimental Medicine (1982)

We have reported that abnormal lymphocyte function in Sjogren's syndrome occurs almost exclusively in patients with HLA-B8. We now report that most clinically normal individuals with this antigen have a similar impairment of cellular immunity. This finding suggests that the lymphocyte abnormality in Sjogren's syndrome is not secondary to the disease process or medication and might have primary etiological significance. The lymphocyte abnormality is expressed as a decreased proliferative response to suboptimally stimulating concentrations of phytohemagglutinin (PHA) and concanavalin A (Con A). In contrast, the response to optimally stimulating concentrations of PHA and Con A is unaffected. The imparied mitogen responsiveness appears to be intrinsic to the T lymphocytes, as it can be demonstrated in purified T cell preparations.
Downsizing: policy options to reduce portion sizes to help tackle obesity
Authors: Theresa M Marteau, Gareth J Hollands, Ian Shemilt, Susan A Jebb
Journal: BMJ (2015)

The worldwide prevalence of obesity and overweight has risen substantially over the past three decades with no country yet achieving a reduction. 1International and national ambitions to "end childhood obesity" 2 and "reduce non-communicable diseases by 25% by 2025" 3 are unmatched by policies that could realise them.The causes of obesity are complex but overconsumption of food and sugary drinks is a critical proximal determinant, driven in part by large portion sizes.The importance of developing interventions and policies to reduce the size, availability, and appeal of large portions is underscored by the compelling evidence that people eat and drink more from larger portions.
Predicting risk of chemotherapy-induced side effects in patients with colon cancer with single-nucleotide polymorphism (SNP) Bayesian networks (BNs).
Authors: Stephen T. Sonis, Lee Steven Schwartzberg, Mark S. Walker, Susan M Weidner, Gil Alterovitz
Journal: Journal of Clinical Oncology (2013)

344 Background: Patients receiving standard chemotherapy for colon cancer are at significant, but unequal, risk for development of treatment-induced side effects. Currently, there is no accurate way to identify these risks for individual patients. This study adopted a novel approach to creating a risk prediction model for chemotherapy-induced side effects through the development of clusters of SNPs defined by BNs. It was designed to assess the feasibility of identifying SNP-BNs that could accurately predict the risk for 6 common, and often debilitating, side effects: chemotherapy-induced nausea/vomiting (CINV), diarrhea, oral mucositis (OM), cognitive dysfunction (CD), peripheral neuropathy (PN), and fatigue. Methods: Patients (n=57) with colon cancer who received at least 3 cycles of FOLFOX6 +/- bevacizumab (along with standard supportive care strategies) were enrolled. Saliva samples were collected, DNA was isolated, and SNPs were analyzed on Illumina Omni microarrays (2.5 x 10 6 SNPs). Side effects under consideration were observed using Patient Care Monitor, a validated patient-reported symptom assessment instrument. BNs were developed for each of the 6 side effects and cross-validated using robust statistical analyses. Results: The percentage of patients who experienced moderate-to-severe side effects was notable despite supportive care measures. These included the following: CINV (32%), diarrhea (16%), OM (26%), CD (21%), PN (26%), and fatigue (56%). SNP-BNs were defined for each of the 6 side effects and were found to predict risk with a high degree of accuracy (&gt;90%) and receiver operating characteristic (ROC) curves (&gt;0.920). Conclusions: This study calls attention to the fact that treatment-related side effects persist in patients receiving FOLFOX6 +/- bevacizumab for colon cancer. SNP-BNs were identified that could accurately predict 6 of the most common treatment-related side effects. This genomic-based tool has the potential to offer clinicians accurate and actionable information for individualizing a patient’s cancer care plan.
Cancer Screening: When Is the Juice Worth the Squeeze?
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2014)

in individuals with different life expectancies. The investigators, from the University of North Carolina, used a validated mortality index specific for the National Health Interview Survey (http://www.cdc.gov/nchs/nhis/about_nhis.htm) and queried data from the same survey (2000–2010) for rates of cancer screening (for breast, prostate, cervical, and colorectal cancers) in individuals with low (≤25%), intermediate (26%– 49%), high (50%–74%), and very high (≥75%) risk of 9-year mortality. Now, although controversy exists about some forms of cancer screening and the role these play in minimizing mortality, screening for selected cancers is accepted practice and considered to be an important part of health care maintenance. But if a patient is too sick to treat the cancer you are screening for, wouldn’t you recommend against screening? Surprisingly, the investigators found that up to 55% of patients with a very high risk of 9-year mortality had received some form of cancer screening. Even more odd, approximately one-third of women who had undergone a hysterectomy and presumably didn’t have a cervix were screened for cervical cancer. What were their doctors thinking? I don’t know what we spend on cancer screening in the United States, but I bet it’s a lot. A prostate-specific antigen (PSA) screen doesn’t cost much in itself, but the downstream cascade of procedures (biopsies, surgeries, and other treatments) can be costly. Considering the high cost of health care in this country, it seems prudent to sit back and think these things through a bit. I admit that it can be challenging to explain to the public that at a certain age or in consideration of comorbidities, screening for cancer is no longer indicated. It could be a long discussion. But I think that with enough education and assurance that we won’t abandon individuals with symptoms of cancer, this practice could be adopted. And perhaps for the elderly or very frail public, having a few less things to worry about might be appreciated. My elderly patient died from metastatic colon cancer a couple years after he asked me about purchasing his new suit and dental repairs. In case you were wondering, after finding out that he wanted the new suit so he would look nice for a family wedding and his teeth fixed so he could enjoy the things he liked to eat, I recommended that he do both. It seemed worth it to me. But I think that if he had asked about measuring his PSA, I would have suggested that he had more important things to worry about. And he would have agreed.
Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study
Authors: P Lippe, D Tummarello, M C Monterubbianesi, R R Silva, L Giuliodori, D Mari, A Santo, F Pasini, G L Cetto, D Rossi, E Porfiri, S Cascinu, R Cellerino
Journal: Annals of Oncology (1999)
Evaluating lung function response to umeclidinium/vilanterol (UMEC/VI) 62.5/25mcg, UMEC 62.5mcg and VI 25mcg in COPD patients
Authors: J.F. Donohue, D. Singh, C. Munzu, S. Kilbride, A. Church
Journal: European Respiratory Journal (2014)

Background: UMEC (a LAMA) is in development as monotherapy and in combination with VI (a LABA) for COPD. Data from two similar studies are presented.

Objective: To determine if UMEC/VI provides additional benefit in COPD patients (pts) responsive (≥12% and ≥200mL increase in FEV1 from baseline) to UMEC or VI alone.

Methods: In both 12 week randomised, double-blind, 3-way complete block, cross-over studies, COPD pts with FEV1 ≤70% pred. received UMEC 62.5mcg, VI 25mcg and UMEC/VI 62.5/25mcg once daily via ELLIPTA™ DPI during three 14-day treatment periods (with 10–14 day washout). Primary endpoint: weighted mean FEV1 over 0–6h post-dose on Day 14 of each treatment period. Safety assessments included AEs, vital signs and COPD exacerbations.

Results: ITT: N=207; N=182. Primary endpoint: see table.

![Figure][1] 



Incidence of on-treatment AEs was similar across treatments in studies '132 (12–18%) and '133 (16–18%). There were no unexpected effects on vital signs. Exacerbations (on/post-treatment): 3 in study '132 (1 per treatment group); 6 in study '133 (3 UMEC, 2 VI, 1 UMEC/VI). Deaths: 1 in '133 (UMEC group; not drug related).

Conclusions: UMEC/VI 62.5/25mcg statistically significantly improved lung function in COPD pts identified as responders or non-responders to UMEC 62.5mcg and/or VI 25mcg monotherapy. No new safety concerns were identified.

Funding: GSK (DB2116132 [[NCT02014480][2]];DB2116133 [[NCT01716520][3]]).

 [1]: pending:yes
 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02014480&atom=%2Ferj%2F44%2FSuppl_58%2FP291.atom
 [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01716520&atom=%2Ferj%2F44%2FSuppl_58%2FP291.atom
Left Atrial Appendage Occlusion Devices Versus Pharmacological Agents for Stroke Prevention in Atrial Fibrillation
Authors: Andrea Messori, Sabrina Trippoli
Journal: Journal of the American College of Cardiology (2015)

In evaluating the effectiveness of the Watchman appendage occlusion device (AOD) in patients with atrial fibrillation, the main strength of the study by Holmes et al. [(1)][1] is represented by the large population of patients included in the analysis (which tends to approximate the totality of
Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism
Authors: Paul D. Stein, Thomas L. Chenevert, Sarah E. Fowler, Lawrence R. Goodman, Alexander Gottschalk, Charles A. Hales, Russell D. Hull, Kathleen A. Jablonski, Kenneth V. Leeper, David P. Naidich, Daniel J. Sak, H. Dirk Sostman, Victor F. Tapson, John G. Weg, Pamela K. Woodard
Journal: Annals of Internal Medicine (2010)

The accuracy of gadolinium-enhanced magnetic resonance angiography (MRA) and magnetic resonance venography for diagnosing pulmonary embolism has not been determined conclusively. In this multicente...
Negative Thyroid Transcription Factor 1 Expression Defines an Unfavorable Subgroup of Lung Adenocarcinomas
Authors: Yiliang Zhang, Rui Wang, Yuan Li, Yunjian Pan, Haichuan Hu, Yang Zhang, Hang Li, Lei Shen, Yongfu Yu, Yihua Sun, Haiquan Chen
Journal: Journal of Thoracic Oncology (2015)

Thyroid transcription factor 1 (TTF1) is a master regulator of pulmonary differentiation that is downregulated in a subset of lung adenocarcinoma, of which the clinicopathologic characteristics were not fully clarified.One thousand forty-two lung adenocarcinoma patients who underwent surgery were investigated for clinic characteristics, histologic subtyping, and spectrum of well-identified driver mutations. TTF1 expression was correlated with these clinicopathologic factors and survival.Compared with TTF1 positive (TTF1+) patients, the 133 negative individuals (12.8%, TTF1-) were more likely to be male (p = 0.006) and heavy smokers (p = 0.002) who had larger tumor size (p < 0.001) and more advanced disease stage (p < 0.001). TTF1- presented more in solid and invasive mucinous-predominant carcinomas (both p < 0.001), whereas TTF1+ was identified in 100% patients with adenocarcinoma in situ, minimally invasive and lepidic-predominant adenocarcinomas. The TTF1- tumors harbored the known driver mutations in significantly low frequency compared with TTF1+ adenocarcinomas (57.8% versus 78.1%, p < 0.001), especially in epidermal growth factor receptor (EGFR) mutations (37.6% versus 60.7%, p < 0.001). There was no significant difference in recurrence-free survival between the TTF1- and TTF1+ patients, either for the whole cohort or stratified by pathologic stage, or among the driver mutation-defined subsets. However, recurrence of multiple metastases was more likely to occur in patients with TTF1- adenocarcinomas (88.1% versus 32.4%, p < 0.001). Multivariate analysis revealed that TTF1- independently predicted both poor postrecurrence survival (hazard ratio = 1.664; 95% confidence interval , 1.097-2.524; p = 0.017) and unfavorable overall survival (hazard ratio = 1.553; 95% confidence interval , 1.013-2.381; p = 0.043).TTF1- correlated with solid and invasive mucinous subtypes of lung adenocarcinoma and lower frequency of EGFR mutations. It defines a subgroup of lung adenocarcinomas with unfavorable outcomes.
Accuracy of diagnostic testing in primary ciliary dyskinesia
Authors: Claire L. Jackson, Laura Behan, Samuel A. Collins, Patricia M. Goggin, Elizabeth C. Adam, Janice L. Coles, Hazel J. Evans, Amanda Harris, Peter Lackie, Samantha Packham, Anton Page, James Thompson, Woolf T. Walker, Claudia Kuehni, Jane S. Lucas
Journal: European Respiratory Journal (2015)

Diagnosis of primary ciliary dyskinesia (PCD) lacks a “gold standard” test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach. Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests. HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min −1 cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific. In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min −1 ) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.