tbuckley/cabot-search huggingface dataset:
Comparison of Survival and Quality of Life in Advanced Non–Small-Cell Lung Cancer Patients Treated With Two Dose Levels of Paclitaxel Combined With Cisplatin Versus Etoposide With Cisplatin: Results of an Eastern Cooperative Oncology Group Trial
Authors: Philip Bonomi, KyungMann Kim, Diane Fairclough, David Cella, John Kugler, Eric Rowinsky, Michael Jiroutek, David Johnson
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non–small-cell lung cancer (NSCLC). To determine whether a new agent, paclitaxel, would further improve survival in NSCLC, the Eastern Cooperative Oncology Group conducted a randomized trial comparing paclitaxel plus cisplatin to a standard chemotherapy regimen consisting of cisplatin and etoposide. PATIENTS AND METHODS: The study was carried out by a multi-institutional cooperative group in chemotherapy-naive stage IIIB to IV NSCLC patients randomized to receive paclitaxel plus cisplatin or etoposide plus cisplatin. Paclitaxel was administered at two different dose levels (135 mg/m 2 and 250 mg/m 2 ), and etoposide was given at a dose of 100 mg/m 2 daily on days 1 to 3. Each regimen was repeated every 21 days and each included cisplatin (75 mg/m 2 ). RESULTS: The characteristics of the 599 patients were well-balanced across the three treatment groups. Superior survival was observed with the combined paclitaxel regimens (median survival time, 9.9 months; 1-year survival rate, 38.9%) compared with etoposide plus cisplatin (median survival time, 7.6 months; 1-year survival rate, 31.8%; P = .048). Comparing survival for the two dose levels of paclitaxel revealed no significant difference. The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients (P = .152). For the stage IV subgroup, the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel (P = .246). With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias, neurotoxicity, and, possibly, increased treatment-related cardiac events with high-dose paclitaxel, toxicity was similar across all three arms. Quality of life (QOL) declined significantly over the 6 months. However, QOL scores were not significantly different among the regimens. CONCLUSION: As a result of these observations, paclitaxel (135 mg/m 2 ) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial.
The prevalence of cough in lung cancer: Its characteristics and predictors.
Authors: Amelie Sylvia Mary Harle, Oliver Buffin, Jack Burnham, Alex Molassiotis, Fiona Helen Blackhall, Jaclyn A Smith
Journal: Journal of Clinical Oncology (2014)

162 Background: Cough commonly affects patients with LC but quoted prevalence figures vary and most were obtained before advances in anticancer treatment for LC. This study aimed to determine its prevalence and characteristics (severity, impact and potential predictors) in patients undergoing standard treatment and follow up. Methods: Consecutive LC patients attending clinics at The Christie Hospital, UK during a predefined 5 week period were asked whether they had a cough and invited to participate in its further evaluation according to an ethically approved protocol. Demographic, cancer and cancer treatment data were collected in all. Patients with a cough also completed subjective assessments using the validated cough impact Manchester cough in LC scale (MCLCS) and cough severity visual analogue scale (VAS). Standard statistical tests were used for analysis with significance (p&lt;0.05). Results: Of 223 consecutive LC outpatients approached, the prevalence of cough was 57% (128/223); 202/223 (86%) consented to further data collection (study population) and of these 115 (57%) reported cough. The majority (60/115, 52%) felt that their cough warranted treatment and 23% reported their cough to be painful (26/115). The median VAS score (n=115) was 32mm (25th-75th IQR 20-51, range 0-100, high scores = worse cough severity). The median MCLCS score (n=113) was 22 (25th-75th IQR 16-27, range 1-50, high scores = worse cough impact). There was no significant difference between coughers and non-coughers with respect to age, sex, co-morbidities, smoking, performance status, treatment intent, treatment type, reasons for not receiving treatment, stage and histology. The proportion of non-coughers was lower among patients receiving anticancer therapy (45/115 39% vs 47/87 54%, p=0.04) in univariate analysis. Conclusions: Cough is present in the majority of LC patients, even in those undergoing treatment. Many patients feel that it warrants treatment. Whilst many consider factors such smoking, stage, histology and cancer treatment type to be important determinants of the presence of cough, our data does not reflect this. Improving LC related cough requires more than better cancer therapies.
Hand eczema in twins: a questionnaire investigation
Authors: L.E. Bryld, T. Agner, K.O. Kyvik, L. Brøndsted, C. Hindsberger, T. Menné
Journal: British Journal of Dermatology (2000)

Hand eczema in a population-based twin cohort of 6666 persons aged 20-44 years was investigated by means of a questionnaire regarding skin symptoms on the hands and self- or physician-diagnosed hand eczema. Genetic influence was observed by significant differences between identical and fraternal twins regarding casewise concordance rate and correlations in liability under the threshold model. The casewise concordance rates were almost twice as high in identical compared with fraternal twins in both sexes. By extension of the threshold model a joint analysis could be performed, resulting in a heritability estimate of 0.65. Tendencies towards stronger genetic influence for men and for younger individuals were present, but neither was statistically significant. No particular symptom pattern expressed especially strong or weak genetic influence. Hereditary factors for hand eczema were observed despite a presumably substantial individual-specific environmental variation. The hypothesis that hereditary risk factors may play a significant part in the development of hand eczema in the general population, when no extreme environmental exposure exists, seems justifiable. The relevance of known individual risk factors such as atopic dermatitis or contact allergy in relation to heredity remains to be analysed. The possible importance of age and temporal change also needs further consideration.
Indomethacin is a Placental Vasodilator in the Dog
Authors: John G. Gerber, Robert A. Branch, Walter C. Hubbard, Alan S. Nies
Journal: Journal of Clinical Investigation (1978)

The effect of 8 mg/kg of indomethacin on uterine blood flow, prostaglandin production, and intraamniotic fluid pressure was examined in late pregnant dogs. Uterine blood flow was measured with 15 μm radiolabeled microspheres. Because we found that a significant percentage of the microspheres shunted through the placental circulation into the lungs, we calculated placental blood flow by adding the shunted microspheres through the placenta to the nonshunted microspheres in the placenta. Total uterine blood flow significantly increased from 271±69 ml/min during control period to 371±72 ml/min (P < 0.01) 30 min after indomethacin. This increase was attributable to the change in blood flow to the placental circulation (222±58 to 325±63 ml/min; P < 0.01). Associated with these hemodynamic changes we found an almost complete suppression of uterine prostaglandin E2 production (1,654±305 to 51±25 pg/ml; P < 0.01) as measured by gas chromatography-mass spectrometry. In addition, we found that indomethacin treatment resulted in uterine relaxation as measured by intraamniotic fluid pressure changes (11.2±1.3 mm Hg to 8.5±1.2 mm Hg; P < 0.001).
Rapid Switching From Morphine to Methadone in Cancer Patients With Poor Response to Morphine
Authors: Sebastiano Mercadante, Alessandra Casuccio, Luciano Calderone
Journal: Journal of Clinical Oncology (1999)

The aim of this study was to evidence the clinical effects of an abrupt substitution of morphine with methadone using a fixed ratio of 1:5 in patients for whom limiting adverse effects occurred before adequate analgesia was achieved with oral morphine.A cross-sectional prospective study was carried out on 24 consecutive patients who were switched from oral morphine to oral methadone because they experienced substantial adverse effects that limited further increase in morphine dose. A fixed conversion morphine-to-methadone ratio of 5:1 was chosen. Subsequently, doses were changed according to clinical need, with frequent visits or phone contacts. Pain and symptom intensity, preswitching doses of morphine, initial and subsequent doses of methadone, and survival were recorded.A significant decrease in pain and symptom intensity was found within 24 hours after the substitution took place. The switching was effective in most patients (19 of 24), although five patients required alternative treatments. No significant changes in methadone dose were reported in the 3 days after switching. Methadone dose was significantly higher in patients who had lower preswitching doses of morphine and vice versa. No relevant complications were reported.A rapid substitution of morphine with methadone using an initial fixed ratio of 5:1 is a safe and effective method for improving the balance between analgesia and adverse effects in cancer patients with poor morphine response. An appropriate system of patient monitoring is necessary, because further changes in dose may be required according to clinical needs.
Hemodynamic effects of pneumonia
Authors: Herbert Benson, Mohammed Akbarian, Lawrence N. Adler, Walter H. Abelmann
Journal: Journal of Clinical Investigation (1970)

Since an excessive mortality from pneumonia persists in spite of antimicrobial therapy, the hemodynamics during and after the acute phase of pneumonia were studied in 17 patients. None of the patients had clinical heart disease and all had normal venous pressures. The arteriovenous oxygen difference was used to assess the adequacy of the circulation to meet peripheral tissue perfusion, and a spectrum of arteriovenous oxygen differences was noted. In 11 patients, tissue perfusion was considered adequate because the arteriovenous oxygen difference did not exceed 5.5 vol%. In six patients, the arteriovenous oxygen difference was greater than 5.5 vol% and these six patients differed hemodynamically from the others. In these six patients during the acute phase of pneumonia, cardiac output was decreased, and total peripheral resistance and hematocrit were increased. When five patients with varying arteriovenous oxygen difference were studied during exercise in the acute phase, cardiac output increased while venous pressure remained unchanged. Arteriovenous oxygen difference in these five exercising patients increased in all, but most markedly in those with an initially widened arteriovenous oxygen difference. The inadequate response to pneumonia is most consistent with depressed myocardial function, but the possibility of decreased intravascular volume as a contributory factor could not be excluded.
Abstract 1484: CD57 defines a novel maker of glioblastoma stem cells that have greater invasive potential than CD133+ tumor cells
Authors: Lin Qi, Yu-lun Huang, Mari Kogiso, Hua Mao, Patricia Baxter, Jack MF Su, Laszlo Perlaky, Ching C. Lau, Murali Chintagumpala, Xiao-Nan Li
Journal: Cancer Research (2014)

Abstract Glioblastoma multiforme (GBM) is the most aggressive and lethal brain tumor that occurs both in children and adults. Diffuse invasion into normal brain tissue is one of the important biologic features that make GBM refractory to conventional therapies. While existing studies on GBM invasion are primarily conducted using tumor core tissues from surgical resections, it is unclear whether unresectable, infiltrative GBM cells would be more informative for studying their invasive nature compared to those in the resected tumor cores. More importantly, little is known if and which cancer stem cell populations are driving glioma invasion. To address these fundamental issues, we utilized our panel of 7 (6 pediatric and 1 adult) patient tumor-derived orthotopic xenograft mouse models of GBM to isolate invasive GBM cells (infiltrating normal mouse brain parenchyma) and tumor core GBM cells and directly compared their biological differences. Our result showed that the invasive cells have stronger neurosphere forming efficiency in vitro in a serial dilution assay and increased tumorigenic capacity after in vivo transplantation (particularly at 100 cells/mouse) compared to the tumor core cells. A screening of putative cancer stem cell markers (CD133, CD15, CD24/CD44, CD57 and CD117) showed that invasive GBM cells are enriched (&amp;gt;2 folds) with CD57+ cells compared to the tumor core cells, and these infiltrating cells were predominantly CD57+/CD133-. Even the CD133+ cells were frequently dual-positive with CD57 (CD33+CD57+), not only in the xenograft tumors but also in a separate set of patient GBM samples. Mechanistically, we found that CD57+ cells expressed high levels of self-renewal genes and tend to stay in G0/G1 phases. In conclusion, we showed that invasive GBM cells are biologically deferent from the matched tumor core cells and identified CD57 as a novel stem cell marker that is associated with GBM infiltration. Our findings suggest that new anti-invasion therapies should target CD57+ cells in addition to CD133+ cells in GBM. Citation Format: Lin Qi, Yu-lun Huang, Mari Kogiso, Hua Mao, Patricia Baxter, Jack MF Su, Laszlo Perlaky, Ching C. Lau, Murali Chintagumpala, Xiao-Nan Li. CD57 defines a novel maker of glioblastoma stem cells that have greater invasive potential than CD133+ tumor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1484. doi:10.1158/1538-7445.AM2014-1484
Familial Retrocaecal Appendicitis
Authors: Y Shperber, A Halevy, J Oland, R Orda
Journal: Journal of the Royal Society of Medicine (1986)

Four members of the same family operated on for acute retrocaecal appendicitis are reported. It is suggested that they provide further support for the hypothesis that an hereditary factor might be involved in the pathogenesis of acute appendicitis.
Levomepromazine (Nozinan) reduces nonspecific bronchial hyperreactivity in asthmatics
Authors: P Faurschou, F Madsen, H Pals, A Rosetzsky
Journal: European Respiratory Journal (1989)

Ten patients with bronchial asthma were challenged with histamine before and after receiving saline and active drug (levomepromazine or antazoline) (a total of six challenges). The antihistaminic effect of levomepromazine (25 mg) was found to be comparable to that of antazoline (100 mg), evaluated from skin prick tests. Prechallenge forced expiratory volume in one second (FEV1) was found to be larger after levomepromazine than after antazoline (p less than 0.05), indicating a direct bronchodilating effect. This increased threshold airway calibre may have influenced the results of challenge, but change in provocative concentration producing 20% fall (PC20) was not statistically significantly correlated to change in FEV1. Levomepromazine increased PC20 2-doubling concentration compared to antazoline (p less than 0.05). Variation was observed in two minutes' ventilation during tidal volume breathing challenge. However, there was no statistically significant variation in two minutes' ventilation during challenge after receiving levomepromazine or antazoline. It was concluded that levomepromazine possesses a bronchodilating capacity and reduces bronchial hyperreactivity.
Surveillance Intervals for Small Abdominal Aortic Aneurysms
Authors: Matthew J Bown, Michael J Sweeting, Louise C Brown, Janet T Powell, Simon G Thompson
Journal: JAMA (2013)

<h3>Importance</h3>Small abdominal aortic aneurysms (AAAs [3.0 cm-5.4 cm in diameter]) are monitored by ultrasound surveillance. The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture.<h3>Objective</h3>To limit risk of aneurysm rupture or excessive growth by optimizing ultrasound surveillance intervals.<h3>Data Sources and Study Selection</h3>Individual patient data from studies of small AAA growth and rupture were assessed. Studies were identified for inclusion through a systematic literature search through December 2010. Study authors were contacted, which yielded 18 data sets providing repeated ultrasound measurements of AAA diameter over time in 15 471 patients.<h3>Data Extraction</h3>AAA diameters were analyzed using a random-effects model that allowed for between-patient variability in size and growth rate. Rupture rates were analyzed by proportional hazards regression using the modeled AAA diameter as a time-varying covariate. Predictions of the risks of exceeding 5.5-cm diameter and of rupture within given time intervals were estimated and pooled across studies by random effects meta-analysis.<h3>Results</h3>AAA growth and rupture rates varied considerably across studies. For each 0.5-cm increase in AAA diameter, growth rates increased on average by 0.59 mm per year (95% CI, 0.51-0.66) and rupture rates increased by a factor of 1.91 (95% CI, 1.61-2.25). For example, to control the AAA growth risk in men of exceeding 5.5 cm to below 10%, on average, a 7.4-year surveillance interval (95% CI, 6.7-8.1) is sufficient for a 3.0-cm AAA, while an 8-month interval (95% CI, 7-10) is necessary for a 5.0-cm AAA. To control the risk of rupture in men to below 1%, the corresponding estimated surveillance intervals are 8.5 years (95% CI, 7.0-10.5) and 17 months (95% CI, 14-22).<h3>Conclusion and Relevance</h3>In contrast to the commonly adopted surveillance intervals in current AAA screening programs, surveillance intervals of several years may be clinically acceptable for the majority of patients with small AAA.
Abstract P128: Prevalence of Posttraumatic Stress Disorder Due to Stroke: A Meta-analysis
Authors: Donald Edmondson, Safiya Richardson, Jennifer K Fausett, Louise Falzon, Virginia J Howard, Ian M Kronish
Journal: Circulation (2013)

Title: Prevalence of posttraumatic stress disorder due to stroke: A meta-analysis Objective: To estimate the prevalence of stroke-induced posttraumatic stress disorder (PTSD) using systematic review and meta-analysis. Methods: Potentially relevant peer-reviewed journal articles were identified by searching the Ovid MEDLINE, PsycINFO, PILOTS Database, The Cochrane Library and Scopus from inception to April 2012; all searches were conducted on April 13, 2012. Observational cohort studies that assessed PTSD with specific reference to a stroke or TIA that occurred at least 1 month prior to the PTSD assessment were included. We abstracted PTSD rates and characteristics of the study and sample from all included studies. The coding of all articles included demographic information, sample size, study country, and method and timing of PTSD assessment. Results: Eight studies (N= 1,111) met our inclusion criteria. PTSD prevalence estimates varied significantly across studies by timing of PTSD assessment (ie., within 1 year of stroke vs greater than 1 year post-stroke; 70% of heterogeneity explained; Q 1 =14.68; P &lt;.001). The final aggregate prevalence estimate was 14% (95% CI, 11%-17%) from the random effects model comprised of an aggregate estimate of 25% (95% CI, 17%-35%) for PTSD within 1 year of stroke and 11% (95% CI, 8%-14%) after 1 year. Conclusions: Although posttraumatic stress disorder (PTSD) is commonly thought to be triggered by external events such as combat or sexual assault, these results suggest that as many as 1 in 4 stroke survivors develop significant PTSD symptoms due to the stroke. Further research is needed to determine whether stroke-induced PTSD increase recurrence risk in stroke patients. Figure 1. Stroke-induced PTSD prevalence estimates Note: The area of each square is proportional to the study’s weight in the meta-analysis, and each line represents the confidence interval around the estimate. Diamonds represent aggregate estimates, by PTSD assessment timing and overall.
Interleukin-2 and lymphokine-activated killer cells in 15 children with advanced metastatic neuroblastoma.
Authors: S Negrier, J Michon, D Floret, E Bouffet, J C Gentet, I Philip, P Cochat, D Stamm, J Costil, M Gaspard
Journal: Journal of Clinical Oncology (1991)

A phase II trial using interleukin-2 (IL2) and lymphokine-activated killer (LAK) cells was carried out in an attempt to treat children with end-stage neuroblastoma. Fifteen patients (median age, 7 years) were enrolled in the study. Twelve were in relapse after massive chemotherapy and autologous bone marrow transplantation (ABMT), and three had a primary refractory disease after conventional chemotherapy. IL2 was administered as an 18 x 10(6) IU/m2/d continuous infusion. One course consisted of a double 5-day treatment period separated by a 6-day break. Cytapheresis to harvest LAK progenitor cells was performed during the rest period. After a 4-day in vitro culture, LAK cells were reinjected during the second cycle of therapy. A phenotypic and functional analysis of immunologic parameters was conducted along with the therapeutic protocol. Toxicity was significant with two toxic deaths (cardiotoxicity and respiratory distress). The reinfusion of large amounts of LAK cells was clearly involved in one case, but this particularly severe toxicity has to be related to the patient's status (ie, heavy pretreatment). No significant clinical response was seen. The immunologic monitoring showed phenotypic and functional modifications in these patients before initiation of treatment and an unexpected absence of evolution of these parameters during IL2 therapy. Although the origin of these immune dysfunctions is not clear, they could be involved in the failure of IL2 therapy. Future studies of IL2 therapy in neuroblastoma should be undertaken earlier in the course of the disease.
Traumatic Dissociation: Neurobiology and Treatmentedited by Eric Vermetten, M.D., Ph.D., Martin J. Dorahy, Ph.D., and David Spiegel, M.D. Arlington, Va., American Psychiatric Publishing, 2007, 398 pp., $62.00.
Authors: SAMUEL R. CHAMBERLAIN
Journal: American Journal of Psychiatry (2007)
Increased prevalence of airway hyperresponsiveness in severely obese women: Preliminary results
Authors: Mohamed Essalhi, Florence Gillaizeau, Brigitte Chevalier-Bidaud, Bruno Mahut, Christophe Delclaux
Journal: European Respiratory Journal (2011)

The reductions in lung volumes observed in obese individuals are associated with a reduction in peripheral airway diameter, a phenomenon that may perturb smooth muscle function, potentially increasing airway hyperresponsiveness (AHR). We hypothesized that severe obesity could be associated with increased AHR.  Severely obese (BMI≥35, n=119) women with and without physician-asthma diagnosis at any time (32 [27%], 11 diagnosed in childhood), healthy women (37, 30 without AHR, with BMI 0.75) were established in obese women. An additional group of asthmatic women (BMI   Preliminary descriptive results. Among obese women, 54 (45%) exhibited AHR (PD20≤2400 μg) and 47% a decrease in FRC (  In conclusion, this cross-sectional study suggests a twofold increase in prevalence of both AHR and asthma in severely obese women. The analyses of the determinants of AHR and asthma are under way.