tbuckley/cabot-search huggingface dataset:
Long-Term Follow-Up of a Community Assignment, One-Time Endoscopic Screening Study of Esophageal Cancer in China
Authors: Wen-Qiang Wei, Zhi-Feng Chen, Yu-Tong He, Hao Feng, Jun Hou, Dong-Mei Lin, Xin-Qing Li, Cui-Lan Guo, Shao-Sen Li, Guo-Qing Wang, Zhi-Wei Dong, Christian C. Abnet, You-Lin Qiao
Journal: Journal of Clinical Oncology (2015)

Purpose There are no global screening recommendations for esophageal squamous cell carcinoma (ESCC). Endoscopic screening has been investigated in areas of high incidence in China since the 1970s. This study aimed to evaluate whether an endoscopic screening and intervention program could reduce mortality caused by ESCC. Methods Residents age 40 to 69 years were recruited from communities with high rates of ESCC. Fourteen villages were selected as the intervention communities. Ten villages not geographically adjacent to intervention villages were selected for comparison. Participants in the intervention group were screened once by endoscopy with Lugol's iodine staining, and those with dysplasia or occult cancer were treated. All intervention participants and a sample consisting of one tenth of the control group completed questionnaires. We compared cumulative ESCC incidence and mortality between the two groups. Results Three thousand three hundred nineteen volunteers (48.62%) from an eligible population of 6,827 were screened in the intervention group. Seven hundred ninety-seven volunteers from an eligible population of 6,200 in the control group were interviewed. Six hundred fifty-two incident and 542 fatal ESCCs were identified during the 10-year follow-up. A reduction in cumulative mortality in the intervention group versus the control group was apparent (3.35% v 5.05%, respectively; P &lt; .001). Furthermore, the intervention group had a significantly lower cumulative incidence of ESCC versus the control group (4.17% v 5.92%, respectively; P &lt; .001). Conclusion We showed that endoscopic screening and intervention significantly reduced mortality caused by esophageal cancer. Detection and treatment of preneoplastic lesions also led to a reduction in the incidence of this highly fatal cancer.
Late-breaking abstract: The Effect of lung volume deterioration on tidal volume, airway flows and life span in ataxia telangiectasia
Authors: Daphna Vilozni, Moran Lavie, Ifat Sarouk, Bat-El Bar Aluma, Adi Dagan, Yonit Levi, Moshe Askenazi, Miryam Ofek, Ori Efrati
Journal: European Respiratory Journal (2014)

Introduction: Forced Vital Capacity (FVC) gradually decrease in Ataxia telangiectasia (A-T).

Aim: to determine the effect of FVC decline on life span in A-T.

Methods: Clinical data and yearly best spirometry maneuvers (195 visits) were collected retrospectively during 6yrs, from 37 A-T patients (age 4-21y) attending the A-T national clinic in Israel. 11 patients were walking (ambulated); 26 were confined to wheelchair (Wch) from whom 7 patients died. Spirometry included tidal-volume (TV), FVC and mid-flows (FEF25-75) measurements. Findings were related to recurrent respiratory infections (rRI)

Results: Ambulant patients initial and last FVC were 67+8 and 51+17 %predicted (%P) with a TV/FVC ratio of 23+4% and 26+7% respectively (lower than healthy). Deterioration in FVC accelerated from 2yrs after being confined to the Wch. In deceased patients initial FVC was 31+7%p and 19+6%p prior to death (P=0.0125) while TV/FVC ratio increased from 39+9% 5yrs and to 73+11% 2yrs prior to death (p=0.0001). Ambulant patients without rRI (n=6) had FEF25-75 of 121+16%p indicating restrictive pattern. Once rRI occurred (n=31) FEF25-75 values decreased gradually to 69+27%p at the last measure near death (p=0.0001). FEF25–75/FVC ratio was 2.54+0.70 above normal in all patients until 2yrs prior to death when values increased significantly reaching 4.17+2.08 ratios.

Conclusion: Findings indicate that 5yrs prior to death TV/FVC ratios elevate to levels implying respiratory distress. Moderately reduced FEF25-75 may indicate severe airway obstruction. TV/FVC and FEF25-75/FVC ratios increase abruptly 2yrs prior to death. Treating physicians should be aware of these red flags.
Diameter, Thickness, Area, and Volume of Skin‐Prick Histamine Weals
Authors: Jørgen Serup
Journal: Allergy (1984)

Twelve healthy persons were prick‐tested on the volar forearm with three concentrations of histamine chloride (0.1 mg/ml; 1.0 mg/ml; 10 mg/ml) and an isotonic sodium chloride control. Weal diameters were measured, and skin thickness representing weal thickness was measured by high frequency ultrasound. Relative increases in weal parameters as measured and calculated between weak and strong concentrations of histamine (0.1 and 10 mg/ml) were: mean diameter 139%, weal thickness 46%, tangential area 443%, cross‐sectional area 218%, and weal volume 680%. All the parameters of weal size measured and calculated showed significant differences between the three concentrations of histamine. However, a better distinction might be obtained by calculating weal volume. Coefficients of variation ranged from 12–28% for the weal diameter, 11–14% for the weal thickness, 24–53% for the tangential area, 14–39% for the cross‐sectional area, and 23–55% for the weal volume. The increase in thickness was correlated to weal diameter up to a diameter of 5 mm ( r = 0.64; P &lt; 0.001), after which weals only expanded tangentially. Weal thickness as measured by ultrasound is a potentially important parameter in experimental studies of inflammatory skin reactions. With this new technique it is possible to compare with normal skin and skin treated with solvent for control. For routine prick‐testing of patients with allergy, measurement of weal diameter is still a valid and easy method.
The fate of inhaled drug: Corticosteroid particle size effects in asthma
Authors: Martyn Biddiscombe, Harpal Kalsi, Sally Meah, Ann Allen, Omar Usmani
Journal: European Respiratory Journal (2013)

Background: Drug particle size influences lung deposition and systemic bioavailability of inhaled aerosols. We investigated the fate of 3 different particle sizes of inhaled fluticasone propionate (FP) in the lungs of asthmatics (AST) & healthy subjects (HS). Methods: AST (n=15, FEV1= 81 %pred) & HS (n=15, FEV1= 100 %pred) each inhaled 4 treatments randomised crossover; FP-50µg monodisperse particle sizes 1.5, 3, 6-µm and FP-250µg pMDI. FP plasma concentrations were quantified from baseline to 12-h post-dose. Results: Smaller FP particles (1.5, 3-µm) achieved significantly (p<0.05) higher peak concentrations (Cmax) and showed greater airway clearance and systemic absorptive bioavailability (AUC0-12h) compared to larger particles (6µm) and pMDI, in both AST & HS [ C max (AST:HS pg/mL) 1.5µm(425:359), 3µm(278:290), 6µm(85:63), pMDI(52:65); AUC(0-12h) (AST:HS pg.h/mL) 1.5µm(923:723), 3µm(891:933), 6µm(222:204), pMDI(182:199)]. In both AST & HS, 1.5µm FP particles showed faster clearance from the plasma compartment compared to other particles, and final 12-h concentrations were similar for all 4 treatments. We previously showed 1.5µm monodisperse aerosols achieve greater total lung and distal airways deposition compared to 6µm particles. Conclusions: The systemic bioavailability of inhaled FP is related to its drug particle size, and may be a function of total lung dose and regional airways deposition. Striking differences in the behaviour of different sized drug particles exist within the airways and can be investigated using pharmacokinetics. Each drug formulation interacts differently with the many airways factors that influence and govern the ultimate fate of inhaled drug transport within and beyond the lungs.
The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells
Authors: John P. Ray, Matthew M. Staron, Justin A. Shyer, Ping-Chih Ho, Heather D. Marshall, Simon M. Gray, Brian J. Laidlaw, Koichi Araki, Rafi Ahmed, Susan M. Kaech, Joe Craft
Journal: Immunity (2015)
Some Biologic, Immunogenic, and Morphologic Effects in Mice After Infection With a Murine Sarcoma Virus. II. Morphologic Studies
Authors: Mearl F. Stanton, L. W. Law, R. C. Ting
Journal: JNCI Journal of the National Cancer Institute (1968)

Pathologic changes, brought about either by inoculation of murine sarcoma virus (Moloney) or by injection of virus-induced tumor tissue, were studied in 204 mice from experiments described in this Journal (40: 1101–1112, 1968). The common lesion at the site of subcutaneous or intramuscular inoculation was composed of mixtures of inflammatory cells and granulation tissue that permeated subcutaneous tissues and muscle. With time, these lesions became organized, irregular masses of indurated granulomatous tissue. This tissue consistently contained atypical mesenchymal cells of a type and size not observed in the usual reaction to injury. The atypical cells were large, often multinucleate, and often had distinctly prominent perinuclear concentrations of cytoplasmic material. Although these cells had characteristics of neoplastic cells, the predominant inflammatory component of the lesions better fitted the designation “atypical granuloma”—a term that connotes the complex structure of the lesions as well as their biologic behavior. Lesions of similar type were frequently observed in the spleen, adrenal glands, liver, internal genitalia, peritoneal surfaces, and retroperitoneal areolar tissues. Although these lesions distant from the site of injection contained scattered atypical and presumably neoplastic mesenchymal cells, their distribution suggested they resulted from dissemination of virus rather than dissemination of neoplastic cells. Some lesions persisted for long periods or recurred at sites of injection. These showed a wide range of response from persistent granulomatous inflammation to inert scarring. Tumors with all morphologic characteristics of either mesenchymal cell sarcomas or hemangiosarcomas seemed to evolve from a small percentage of the granulomas. In many ways, the reaction to the murine sarcoma viruses merits comparison and consideration as a model for the study of the reticuloendothelioses of man.
Consider the turbulent energy not inhalation flow when patients use dry powder inhalers (DPIs)
Authors: Wahida Azouz, Philip Chetcuti, Harold Hosker, Dinesh Saralaya, Henry Chrystyn
Journal: European Respiratory Journal (2012)

During an inhalation the formulation of a DPI is de-aggregated by a turbulent energy created by the interaction between the DPI's internal resistance and the patient's inhalation flow. We have measured the inhalation profiles of asthmatic children (CHILD; n=16; FEV1 79% predicted), asthmatic adults (ADULT; n=53, FEV1 72%) and COPD (n=29, FEV1 42%) when they inhale through an Aerolizer (AERO), Accuhaler (ACC), Turbuhaler (TBH) and Easyhaler (EASY) using their 'real life' DPI inhalation technique. These are low, medium, medium/high and high resistance DPIs. A summary of the inhalation characteristics is presented below.

View this table:

Mean (SD) data





Inhalation flow should not be considered in isolation. The turbulent energy and acceleration rate of the inhalation were the greatest for the DPI with the highest resistance.
Brachial Gradient in Cardiac Surgical Patients
Authors: Yvon Baribeau, Benjamin M. Westbrook, David C. Charlesworth, Michael J. Hearne, William A. Bradley, Christopher T. Maloney
Journal: Circulation (2002)

Background Review of the clinical and therapeutic implications of difference in arm blood pressure detected preoperatively in patients having heart surgery. Methods and Results Prospective study of 53 patients (Group 1) with gradient and comparison with a group of 175 patients without gradient (Group 2). All patients had preoperative carotid duplex interrogation and operative epiaortic scanning. There was no statistical difference regarding age, sex, status, redo, diabetes, ejection fraction, prior myocardial infarct, hyperlipidemia, or creatinine level. Risks factors for Group 1 included peripheral vascular disease ( P &lt;0.0001) and cerebrovascular symptoms ( P =0.0196). Severe carotid disease (&gt;80% stenosis) was seen in 41.5% of Group 1 and 13.7% of Group 2 ( P &lt;0.0001) patients. Severe atherosclerotic proximal aortic disease was found in 39.6% of Group 1 and 10.8% of Group 2 ( P &lt;0.0001) patients. There were 7 patients with strokes in Group 1 (13.20%) and 9 in Group 2 (5.14%; P =0.06). Four patients died in Group 1 (7.54%) and 10 died in Group 2 (5.71%; P =0.74). Conclusion Brachial gradient is a marker for increased carotid and proximal atherosclerotic aortic disease. Preoperative arch study at the time of catheterization is strongly recommended, as well as preoperative carotid Doppler and operative epiaortic ultrasound.
Reply
Authors: Marta Cavallin, Salvatore Piano, Paolo Angeli
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. We appreciate the interest of Vasudevan et al. in our article recently published in hepatology1 on the use of terlipressin by continuous infusion, a schedule we introduced in 2006 in the treatment of hepatorenal syndrome (HRS).2 We read with interest their experience with the outpatient continuous infusion of terlipressin in patients with HRS on the liver transplant (LT) waiting list. However, we want to point out some aspects regarding the applicability of this strategy. First of all, in our experience, a median of 6 days seems a too short period to consider a safe discharge of patients with type 1 HRS, which frequently presents bacterial infections and/or other organ failures. Second, a long‐term intravenous continuous infusion of terlipressin is not needed in most responders because of the achievement of a sustained response after withdrawal of terlipressin and albumin. It may be suitable for patients with continuous recurrence of HRS after any attempt to discontinue terlipressin, a condition we defined in 2011 and that occurs in 13% of HRS episodes.3 The long‐term continuous infusion of terlipressin in outpatients may significantly reduce the hospital stay and the cost of management in these patients, particularly if it is combined with a dedicated LT allocation policy. Otherwise, effective treatment with terlipressin and albumin, by reducing Model for End‐Stage Liver Disease score,3 may affect the position of patients on the waiting list, delaying LT. This is the reason we proposed, in the setting of exceptions to Model for End‐Stage Liver Disease score in patients with HRS, to include long‐term treatment with terlipressin and albumin in the calculation of Model for End‐Stage Liver Disease score, as already provided for renal replacement therapy.4 Our proposal was accepted by the Italian board of experts in LT and adopted in the Italian allocation program for LT.5 Finally, we suggest a note of caution about the outpatient infusion of terlipressin: it has potentially serious side effects. Thus, nowadays, we think that it should be used in hospital, under medical supervision. Waiting for the results of larger prospective studies on the use of terlipressin in outpatients, possibly with an analogue available for intramuscular or subcutaneous administration, continuous infusion of terlipressin should be reserved for very select outpatients with continuous recurrence of HRS.
Pharmacokinetics (PK) of PF-562271, a focal adhesion kinase (FAK) inhibitor, and its effect on CYP3A in patients with advanced nonhematologic malignancies.
Authors: H. Xu, D. Yin, K. J. Pierce, S. M. Shreeve, B. Duncan, A. Bello
Journal: Journal of Clinical Oncology (2010)

2553 Background: FAK transduces signaling from integrins and growth factors to modulate tumor cell invasion, proliferation, and survival. PF-562271, a potent FAK inhibitor, is under development as an anticancer agent. Preclinical studies demonstrated that PF-562271 is an inhibitor of its primary metabolizing enzyme, CYP3A. PF-562271 PK and its effect on CYP3A were investigated in a dose-escalation trial in patients with nonhematologic malignancies. Methods: Escalating doses of PF-562271 were administered orally to a total of 67 patients twice a day (BID) or once a day (QD), with or without food. Serial serum samples were collected after the first dose and at steady state to determine PK of PF-562271. To evaluate the effect of PF-562271 on CYP3A activity, plasma PK of orally administered midazolam were determined prior to PF-562271 administration and after repeated PF-562271 dosing to steady state in 8 patients who received the recommended phase 2 dose of 125 mg BID. Serum PF-562271 and plasma midazolam concentrations were determined using validated HPLC-MS/MS methods. The concentration-time data for PF-562271 and midazolam were analyzed by noncompartmental methods. Results: After a single oral dose, PF-562271 was readily absorbed with the maximum serum concentration achieved in 0.5 to 6 hours. The increases in systemic exposure (AUCinf) were dose proportional over the 5 to 25 mg range, but greater than dose proportional from 35 to 225 mg. After multiple oral doses, PF-562271 demonstrated nonlinear accumulation in exposure; the mean ratio of steady state AUC during a dose interval to AUCinf after the first dose ranged from 1.3 to 5.3, indicating time-dependent PK. Similar PK parameters for PF-562271 were observed at comparable doses given with or without food. When co-administered, PF-562271 (125 mg BID) increased total midazolam plasma exposure approximately 5.9-fold. Conclusions: PF-562271 displayed time- and dose-dependent nonlinear PK, and is a potent CYP3A inhibitor. The nonlinear PK of PF-562271 likely resulted from auto-inhibition of CYP3A. In the limited number of subjects evaluated, food did not substantially alter the PK of PF-562271. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
Quantitative Studies of &lt;italic&gt;In Vitro&lt;/italic&gt; Transformation by Chemical Carcinogens
Authors: J. A. DiPaolo, P. Donovan, R. Nelson
Journal: JNCI Journal of the National Cancer Institute (1969)

The addition of carcinogenic polycyclic hydrocarbons to cells of Syrian hamster embryos resulted in the formation of altered clones not seen with control conditions. The presence of altered clones was not due to the X-irradiated feeder cells or the antibiotics. The addition of carcinogens produced a crisscross pattern of both light and dense clones. Altered clones were obtained with both randombred and inbred hamsters. The frequency of appearance of altered clones was related to the known carcinogenic potency of the compounds tested. Toxicity increased with the amount of the compound and was related to its potency as a carcinogen. At constant carcinogen concentration the number of altered clones increased with the number of cells exposed. Positive results were obtained with carcinogen concentrations yielding about a 50% decrease in cloning efficiency, which suggests that the alteration was due to induction rather than to selection.
Central venous catheter infections in out-patients with pulmonary hypertension treated with continuous iloprost
Authors: Stephan Keusch, Rudolf Speich, Silvia Ulrich Somaini
Journal: European Respiratory Journal (2013)

Background: Intravenous prostanoid therapy is one cornerstone of therapy for patients with precapillary pulmonary hypertension (PH). Long-term central venous catheters expose patients to infectious complications. We report the incidence of catheter-related infection (CRI) and the spectrum of bacteria for ambulatory PH patients treated with Iloprost via non-tunnelled central venous catheters from our Swiss referral centre at Zurich.  Methods: Data from 15 PH patients treated with intravenous iloprost between May 2000 and June 2012 were reviewed.  Results: We found 11 CRI, in 4 cases by two different organisms. Pathogens found were Brevibacterium (55%), Micrococcus luteus (18%), coagulase-negative Staphy-lococcus (9%), Staphylococcus aureus (9%) and unusual organisms like Agrobacterium tumefaciens or Delftia tsuruhatensis. The overall CRI rate was 1.28 per 1000 catheter days or 0.47 per year.  Conclusions: The incidence of CRI using long-term, non-tunneled central venous catheters in PH patients treated with iloprost is low. Uncommon, rare pathogens causing CRI were found in a substantial number of patients.
Long-Term Mortality Study of Oil Refinery Workers. IV. Exposure to the Lubricating-Dewaxing Process
Authors: C. P. Wen, Shan P. Tsai, Nancy S. Weiss, Roy L. Gibson, Otto Wong, William A. McClellan
Journal: JNCI Journal of the National Cancer Institute (1985)

A retrospective cohort mortality study of 1,008 male oil refinery workers who ever worked on the lubricating-dewaxing process of the lube oil department and who have been followed for a period of 43 years is presented. These workers were exposed to a number of solvents, primarily methyl ethyl ketone [(MEK) CAS: 78-93-3] and toluene (CAS: 108-88-3), but at levels far below the current Occupational Safety and Health Administration's standard. The standardized mortality ratio (SMR) for all causes (0.70) and the SMR for cancer (0.86) are much lower than unity when they are compared to the mortality experience of the U.S. population. Also observed in this study were 8 prostate cancer deaths (4.4 expected) with an SMR of 1.82, which was not statistically significant (P = .16). Seven of these 8 prostate cancer deaths occurred among nonwhite males, who showed an SMR of 2.47 (P = .053). However, only 1 prostate cancer death was seen among workers specifically assigned to the MEK units. The remaining deaths occurred among maintenance workers who had lube oil department-wide assignments. This cancer risk increased with increasing duration of employment in the lube oil department. A latency of 20 years or more was also observed for these prostate cancer deaths. In this study the processing of lubricating oils was found to be at least as important as the MEK solvents, and department-wide maintenance workers were as much at risk as the MEK unit workers. In view of this finding and findings obtained by others, it seems prudent to continue to study lubricating-dewaxing process workers, including the medical monitoring of all such workers for prostate cancer.
Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production
Authors: Valentin David, Aline Martin, Tamara Isakova, Christina Spaulding, Lixin Qi, Veronica Ramirez, Kimberly B. Zumbrennen-Bullough, Chia Chi Sun, Herbert Y. Lin, Jodie L. Babitt, Myles Wolf
Journal: Kidney International (2015)