tbuckley/cabot-search huggingface dataset:
Blood-brain barrier-associated efflux transporters: a significant but underappreciated obstacle to drug development in glioblastoma
Authors: Warren P. Mason
Journal: Neuro-Oncology (2015)

The blood-brain barrier (BBB) is variably disrupted in glioblastoma (GBM), and for this reason its importance in preventing drug delivery and subsequent development of effective therapies for this disease has been controversial. Continuous tight junctions between capillary endothelial cells, a basal membrane and extracellular matrix, perivascular neurons, pericytes, and astrocytic foot processes maintain the normal BBB and limit entry of potentially harmful chemicals into the CNS.1 Moreover, the BBB is reinforced by 2 key ATP-binding cassette (ABC) efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), both of which further restrict brain penetration of numerous therapeutics by actively pumping these substrates out of cells.2
A phase II study of combined 5-fluorouracil, doxorubicin, and cisplatin in the treatment of advanced upper gastrointestinal adenocarcinomas.
Authors: C G Moertel, J Rubin, M J O'Connell, A J Schutt, H S Wieand
Journal: Journal of Clinical Oncology (1986)

In a phase II study of 67 patients with upper gastrointestinal carcinomas and measurable disease without previous chemotherapy, we have evaluated the combination of intensive course 5-fluorouracil (5-FU) (300 mg/m2/d for five days) doxorubicin (40 mg/m2 on day 1), and cisplatin (60 mg/m2 on day 1). Courses were repeated every 5 weeks. Among 26 patients with gastric carcinoma, a 50% regression rate was obtained with a median survival for all patients of 9 months. Among 29 patients with pancreatic carcinoma, the regression rate was 21% and the median survival was 4 months. Regressions were also observed in smaller numbers of patients with carcinomas of the gallbladder and ampulla of Vater, as well as in cholangiocellular carcinoma of the liver. Toxic reactions were usually clinically tolerable and consisted primarily of nausea, vomiting, stomatitis, diarrhea, leukopenia, and alopecia. Phase III studies are in progress to place the value of this experimental regimen into clinical perspective.
Bone Marrow Transplant Patients With Life-Threatening Organ Failure: When Should Treatment Stop?
Authors: Amanda R. Perry, Michael M. Rivlin, Anthony H. Goldstone
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To discuss issues surrounding life support in bone marrow transplant (BMT) patients, issues that may determine how far we go to keep a deteriorating BMT patient alive—and when we stop trying. How can we define survival chance in BMT patients, and when should prolongation of life be deemed inappropriate? Who should make the decision to terminate support? And how should life support be terminated? DESIGN: Prognostic factors that predict for almost certain nonsurvival have been identified in BMT patients with life-threatening organ failure. The concept of futility raises the question of how low the chance of survival must be before termination of life support is justified—but the concept is flawed, and the value judgments involved in decision making must also be considered. Then, once a decision is made, the manner of withholding or withdrawing life support is also open to discussion. CONCLUSION: Despite controversies, there are areas in which improvements to current practice might be considered. More data are required to determine survival chances of BMT patients with life-threatening organ failure. Greater attention might be devoted, in pretransplant counseling, to issues of intensive life support, with the patient's own views being ascertained before transplantation. And, because technologic possibilities are now imposing fewer boundaries, the problem of finite resources may need to be readdressed, with treatment limits being set down before transplantation.
Inefficient cough in Duchenne muscular dystrophy (DMD)
Authors: Antonella LoMauro, Marianna Romei, Grazia D'Angelo, Andrea Aliverti
Journal: European Respiratory Journal (2012)

In DMD, impaired cough secondary to muscle weakness leads to serious respiratory complications, namely atelectasis, ineffective airway clearance, pneumonia and tracheal intubations. In order to study which factors influence and determine inefficient cough in DMD we studied 36 DMD patients and 15 healthy controls (C,age:16.3±5.4 yrs). Peak cough flow (PCF) was measured at the mouth while rib cage (RC), abdominal (AB) and total chest wall (CW) volume variations were measured by opto-electronic plethysmography during quite breathing and maximal cough (supine position). PCF was  270 L/min in 9 (efficient cough, E:age:16.1±4 yrs,FVC:70.8±34 %predicted). Tidal volume (VT) was similar in I, E and C. In I, RC, AB and CW inspired volumes preceding cough were significantly lower than controls and inspired AB volume was lower than E (panel A). Thoraco-abdominal asynchrony during cough, quantified by labored breathing index (LBI), and percentage abdominal contribution to VT (%ΔVAB) were respectively higher and lower in I group (panel B and C). In conclusion, in DMD inefficient cough is characterized by impaired inspiration, thoracoabdominal asynchony and lower abdominal contribution to volume variations due to diaphragmatic weakness. %ΔVAB, that does not require patient's collaboration, seems to be a good predictor of inefficient cough.

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Abstract 305: Pressure Overload-Induced Myocardial Hypertrophy Causes an Electrical Remodeling of CLC-3 Chloride Channels in Mouse Heart
Authors: Dayue D Duan, Ying Yu, Guanlei Wang, Lingyu L Ye, Yi-gang Li
Journal: Circulation Research (2014)

Backgrand: Myocardial hypertrophy causes an increase in myocyte volume and constitutive activation of a volume-sensitive outwardly-rectifying anion channel (VSORAC). The underlying molecular mechanisms and function of VSORAC in the electrical remodeling during myocardial hypertrophy and heart failure remain undefined. We tested whether cardiac CLC-3 chloride channels play a role in the hypertrophy-induced electrophysiological remodeling. Methods and Results: The age-matched CLC-3 knockout (Clcn3-/-) mice and their wild-type (Clcn3+/+) littermates were subjected to minimally-invasive transverse aortic banding (MTAB). In 77% (44/57) left ventricular (LV) myocytes isolated from MTAB-Clcn3+/+ mice a large VSORAC current was activated under isotonic conditions. Hypotonic cell-swelling caused no changes in the VSORAC but hypertonic cell-shrinkage significantly inhibited it. This constitutively-activated VSORAC had an anion selectivity of I-&gt;Cl-&gt;Asp-, and was inhibited by tamoxifen, PKC activation and intracellular application of anti-CLC-3 antibody. In the age-matched MTAB-Clcn3-/- mice, a significantly smaller outwardly-rectifying current was present in only 38% (36/94, P&lt;0.05 vs MTAB-Clcn3+/+) LV myocytes. This current was neither increased by hypotonic stress nor inhibited by tamoxifen, PKC or anti-CLC-3 antibody, indicating not a VSORAC or CLC-3 current. Expression of CLC-3 protein was significantly increased in the LV tissues of MTAB-Clcn3+/+ mice but not in Sham-Clcn3+/+ and MTAB-Clcn3-/- mice. Both surface and intracardiac electrophysiological recordings revealed more atrial or ventricular arrhythmias in MTAB-Clcn3-/- mice than in MTAB- and Sham-Clcn3+/+ mice. Conclusions: Pressure-overload-induced myocardial hypertrophy causes an upregulation of CLC-3 expression and constitutive activation of CLC-3 may serve as a novel protective mechanism against the electrical remodeling during myocardial hypertrophy and heart failure.
Asthma and caries: A systematic review and meta-analysis
Authors: Maritta S. Jaakkola, Salla Alavaikko, Leo Tjaderhane, Jouni J.K. Jaakkola
Journal: European Respiratory Journal (2011)

Background:  Currently there is some inconclusive evidence suggesting an effect of asthma on increased caries.   Objective:  We conducted a systematic review and meta-analysis to synthesize the evidence on the relation between asthma and caries.   Methods:  An Ovid Medline database search was performed from 1950 through May 2010 using the MeSH terms “asthma” and “caries”. Summary effect estimates were calculated with fixed- and random-effects models and determinants of heterogeneity were studied in meta-regression analysis.   Results:  The meta-analysis was based on 11 articles providing effect estimates of asthma on primary dentition and 14 articles on permanent dentition. The summary effect estimates of the relation between asthma and caries from the random-effects models were 2.73 (95% CI 1.61, 4.64) and 2.04 (95% CI 1.41, 2.89), respectively. Factors identified as determinants of heterogeneity were geographical region for primary dentition and publication year, sample size, asthma definition used, and information on the use of asthma medication for permanent dentition.   Conclusions:  Based on existing evidence asthma doubles the risk of caries in primary and permanent dentition. Physicians and dentists should pay special attention to preventive measures against caries in asthmatics.
Evidence of the Nonimmune Regression of Chemically Induced Papillomas in Mouse Skin&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Edwin J. Andrews
Journal: JNCI Journal of the National Cancer Institute (1971)

To determine the degree to which host immunity is responsible for papilloma regressionl 3-methylcholanthrene-treated allografts were placed on maximally immunodepressed recipients (thymectomy + 450 R radiation and weekly antithymocyte serum injections). Almost 80% of the papillomas on the allografts regressed. Cellular or humoral immune capacity in the recipient animals could not be detected by conventional means. Therefore, the regressions were probably the result of a nonimmunologic mechanism. The data showed that more papillomas regressed on multiples of 21 ± 4 days, from the day of grafting, than in the intervening periods. This clustering pattern of regressions was not observed in immunocompetent animals. In competent mice, two or more mechcnisms, one of which is immunity, may contribute to the regression of chemically induced skin papillomas.
Pulmonary edema is frequently triggered by marathon running
Authors: Gerald Zavorsky, Eric Milne, Massimo Pistolesi, Federico Lavorini, Joseph Rienzi, Kaleen Lavin, Allison Straub
Journal: European Respiratory Journal (2012)

Despite the mounting evidence that pulmonary edema can be triggered by strenuous exercise, (Acta Physiol, 2007, 189: 305-17) it is still widely debated (J Appl Physiol, 2010, 109: 1276-80). The purpose of this study was therefore to determine if pulmonary edema is triggered by marathon running and, if so, to examine its incidence and severity. Twenty-seven runners completed the 2011 Steamtown Marathon, in Scranton, PA, United States, beginning at an elevation of 452 meters above sea level (8°C, 96% RH) and ending with a net elevation drop of 291 meters at the finish (21°C, 51% RH). All runners finished between 142 and 289 minutes. Posteroanterior (PA) and lateral (LA) radiographs were taken one day before the race (pre), and then at 19 (SD 8), 55 (13), and 98 (15) min post-marathon finish, the delay ensuring that any post-exercise increase in capillary blood volume would return to normal. Two experienced chest image readers (EM, MP) independently interpreted the images. They were blinded as to the times at which the radiographs were taken. The PA+LA radiographs were viewed together as a set at each time-point and were scored on eight different radiological characteristics. When summed together, the scores could range from 0 (no edema) to 32 (severe interstitial edema). Mean edema scores from all subjects increased from 1.5 units pre-exercise to 4.1, 3.7, and 2.8 units at 19, 55, and 98 minutes post-exercise, respectively (p
Investigation of Endometrial Abnormalities in Asymptomatic Women Treated With Tamoxifen and an Evaluation of the Role of Endometrial Screening
Authors: C.D.B. Love, B. B. Muir, J. B. Scrimgeour, R. C.F. Leonard, P. Dillon, J. M. Dixon
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Tamoxifen is the most commonly prescribed adjuvant therapy for women with breast cancer. It has agonist activity on the endometrium and is associated with an increased risk of endometrial cancer. The aim of this study was to evaluate whether screening with transvaginal ultrasound (TV USS) with or without hysteroscopy is worthwhile. PATIENTS AND METHODS: A total of 487 women with breast cancer, 357 treated with tamoxifen and 130 controls, were screened with TV USS, and endometrial thickness was measured. Women with thickened endometrium underwent outpatient hysteroscopy. RESULTS: Length of time on tamoxifen ranged from 5 to 191 months (mean, 66 months), and endometrial thickness ranged from 1 to 38 mm (mean, 7.3 mm). Women treated with tamoxifen had significantly thicker endometrium than did controls (P &lt; .0001). There was a statistically significant (P &lt; .0001) positive correlation between length of time on tamoxifen and endometrial thickness. One hundred forty-five women had endometrium greater than 5 mm on USS, and 134 underwent successful outpatient hysteroscopy, 61 of whom had atrophic endometrium, resulting in a 46% false-positive scan rate. The remaining women all had benign features to explain the USS findings. CONCLUSION: TV USS detects a high incidence (41%) of apparent endometrial thickening in women treated with tamoxifen, although 46% had atrophic endometrium on further assessment, and none of the remaining asymptomatic women had significant lesions. Length of time on tamoxifen relates to endometrial thickening as measured by TV USS. TV USS is a poor screening tool because of the high false-positive rate. The low frequency of significant findings suggests that endometrial screening in asymptomatic women is not worthwhile.
The impact of treatment of chronic obstructive pulmonary disease (COPD) on functional status and quality of life of patients
Authors: Drosos Tsavlis, Mamas Theodorou, Anna Tzoumaka, Hellie Lithoxopoulou, Panagiotis Minogiannis, Vassilios Tsaousis, Anastasia Tektonidou, Daphne Kaitelidou
Journal: European Respiratory Journal (2012)

Purpose:  To determine a possible correlation between objective laboratory data on the health of patients with Chronic Obstructive Pulmonary Disease (COPD) and the subjective perception of disease and quality of life by patients themselves. Also to investigate whether these two factors are consistent and whether there are corresponding changes over time after therapeutic intervention.   Methods : We studied 100 patients with COPD who completed the general health questionnaire SF-36 and the qualified for COPD questionnaire St. George9s (SGRQ) and were classified into four groups (four stages of COPD by GOLD) based on their spirometric performance (FEV 1 ) during the first session of the investigation. After 6 months of specific treatment for each group, the patients returned for a new spirometry and completed the two questionnaires again. The same happened with 20 controls who received absolutely no treatment.   Results:  There was a direct correlation between FEV 1  values with the scores of both SGRQ and SF-36 questionnaires in all study groups during both sessions. Following the therapeutic intervention, improvement of FEV 1  values with corresponding changes in the scores of questionnaires were observed in all patient groups. However, statistically significant differences emerged in only two groups of patients raising issues of medication revision taken by the other two groups.   Conclusion:  It was confirmed that the subjective perception of COPD patients are consistent with objective findings that characterize its course, and therefore both questionnaires used to measure the quality of life are reliable and record the changes.
Trends in Office-Based Psychiatric Practice
Authors: Mark Olfson, Steven C. Marcus, Harold Alan Pincus
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The authors examine trends in the composition and duration of visits to psychiatrists in office-based psychiatric practice. METHOD: An analysis was performed of physician-reported data from the 1985 and 1995 National Ambulatory Medical Care Surveys focusing on visits to physicians specializing in psychiatry. Secular changes in visit characteristics were assessed, and mean visit durations were determined for selected sociodemographic and clinical groups. RESULTS: In the decade between 1985 and 1995, visits in office-based psychiatry became shorter, less often included psychotherapy, and more often included a medication prescription. The proportion of visits that were 10 minutes or less in length increased. A shortening in visit duration was most evident for younger patients, privately insured patients, and patients who were not prescribed a psychotropic medication. In the 1995 survey, 6.8% of the psychiatric visits included patient contact with another health care professional. CONCLUSIONS: Changing financial arrangements and new pharmacologic treatments may have contributed to these changes in practice style. (Am J Psychiatry 1999; 156:451–457)
Autochthonous chikungunya virus transmission may have occurred in Bologna, Italy, during the summer 2007 outbreak
Authors: T Seyler, C Rizzo, A C Finarelli, C Po, P Alessio, V Sambri, M L Ciofi Degli Atti, S Salmaso
Journal: Eurosurveillance (2008)

In Italy, a national surveillance system for chikungunya fever coordinated by the National Public Health Institute has been in place since August 2006. In summer 2007, an outbreak of chikungunya fever affected the Italian provinces of Ravenna, Cesena-Forli and Rimini [1-3]. As of 16 December 2007, health authorities identified 214 laboratory-confirmed cases with date of onset from 15 July to 28 September 2007. Most cases (161) occurred in the two neighbouring villages of Castiglione di Cervia and Castiglione di Ravenna, but limited local transmission also took place in the cities of Ravenna, Cesena, Cervia, and Rimini. In September 2007, two confirmed cases (two women aged 68 and 70) were reported among residents of the city of Bologna (373,026 inhabitants). Both had a history of travel in the affected areas (municipality of Cervia). No unusual increase in the density of Aedes albopictus mosquitoes in the Bologna area was noted at that time (September).
Low Level of Thymidylate Synthase Gene Expression in Tumor Tissues is Associated with Response to Preoperative Chemoradiotherapy Including S-1 or Uft in Patients with Rectal Cancer
Authors: S. Sadahiro, T. Suzuki, A. Tanaka, K. Okada, G. Saito, A. Kamijo, H. Nagase
Journal: Annals of Oncology (2014)
Small airway indices, bronchodilator response and asthma control in children
Authors: Snezhina Lazova, Guergana Petrova, Dimitrinka Miteva, Vera Papochieva, Penka Perenovska
Journal: European Respiratory Journal (2014)

Background: The importance of small airways in bronchial asthma (BA) lately have been established. The contemporary guidelines in BA management include astma control score, baseline spirometry andbronchodilator response (BDR).  Materials and Methods: For a period of 3 years 90 children with BA exacerbation underwent pre- and post-bronchodilator spirometry (sp) and filled asthma control questionnaire.  Results: 66 children (73%) were with normal pre-bronchodilator sp (FEV1% pred ≥80%), 89% of them with MMEF25-75   Conclusion: Asthmatic children often have normal sp, but that does not exclude airway hyper-responsiveness and severe airway obstruction during an acute attack. The BDR is a dynamic indicator of the lability of the airways. MMEF25/75%pred. is a good indicator of bronchial obstruction at baseline FEV1% pred. ≥ 80% and correlates with asthma control level.
Identification of coagulase-negative staphylococci other than Staphylococcus epidermidis by automated ribotyping
Authors: E. Carretto, D. Barbarini, I. Couto, D. de Vitis, P. Marone, J. Verhoef, H. de Lencastre, S. Brisse
Journal: Clinical Microbiology and Infection (2005)
Authors' reply
Authors: R. Mera, E. T H Fontham, L. E Bravo, J. C Bravo, M. B. Piazuelo, M. C. Camargo, P. Correa
Journal: Gut (2007)

54:1536-40) by Bhuiyan and Mencias Vera 1 as well as by Gillen and McColl. 2 Both letters requested individual scores for atrophy and intestinal metaplasia at baseline and at 12 years of follow-up.Table 1 shows the scores.We wish to emphasise that the histopathology score (table 1, fig 1 in the original article) was based on the global diagnosis and reflects the grade of atrophy and dysplasia, and the type and extent of intestinal metaplasia.The inflammatory infiltrate was not part of this histopathology score.Therefore, the resolution of the inflammatory infiltrate does not explain the fall in the average histopathology score.Acute and chronic inflammatory scores were classified separately in the antrum and the corpus according to the updated Sydney System in an ordinal scale (0-3).Figure 2 in the original article shows the average values in the antrum over time (Gut 2005;54:1536-40).Objective evidence of the regression of gastric atrophy was reported by our group in a previous report. 3We showed, in a subset of patients of the same cohort, that subjects cured of Helicobacter pylori infection after 6 years of follow-up showed a major reduction of atrophy indices in the antrum, evaluated by strict morphometric techniques.As our trial was based on precancerous end points, the size and duration in this study are insufficient to assess results on the basis of gastric cancer as an end point.Therefore, comparisons of results among studies with different end points should be made with caution.Finally, we apologise for the error that Gillen and McColl brought to our attention, which does not affect any of our conclusions.The correct number of subjects with intestinal metaplasia at baseline who were Helicobacter pylori negative at 12 years is 37/182 or 20% (instead of 70/182).We hope these clarifications help in the interpretation of our findings and conclusions.
Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families
Authors: M. Ammar, C. Bouchlaka-Souissi, C.A. Helms, I. Zaraa, C.T. Jordan, H. Anbunathan, R. Bouhaha, S. Kouidhi, N. Doss, R. Dhaoui, A. Ben Osman, A. Ben Ammar El Gaied, R. Marrakchi, M. Mokni, A.M. Bowcock
Journal: British Journal of Dermatology (2012)

Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region.To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia.Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome.No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A.Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.