tbuckley/cabot-search huggingface dataset:
The effects of insecure attachment on child asthma: Depression and autonomic dysregulation as potential mechanisms
Authors: Bruce Miller, Beatrice Wood, ChiunYu Hsu
Journal: European Respiratory Journal (2013)

Attachment disturbance such as, infant-mother separation causes prolonged depressed behavior and sympathetic withdrawal plus vagal activation(i.e.vagal bias).Vagal neural pathways mediate airway constriction in asthma. Miller’s ANS Dysregulation Model posits that depression, accompanied by ANS vagal bias potentiates airway instability. Purpose: Our study tests the hypothesis that insecure attachment is linked to child depression, which potentiates vagal bias and pulmonary compromise under stress. Method: 171 child asthmatics watched the film “E.T.” The ET death scene elicited separation/loss-related emotions. Self-report indexed insecure attachment (IS), and the CDI indexed depression (D). Asthma disease activity (ADA) was assessed using NHLBI criteria. Children viewed the film while ECG and impedance measures indexed sympathetic activation (pre-ejection period,PEP) and vagal activation(RSA). ANS vagal bias was measured: Zrsa-Zpep (i.e.,RSA minus PEP standardized scores). Respiratory resistance (Rint) indexed pulmonary function. Results: Children with IA had higher D (t=3.6,p=.001), greater vagal bias in the death scene (t=1.9,p=.06) and greater ADA (t=2.1,p=.04) When stratified by D score, D versus non-D children had greater vagal bias in response to ET death scene (t=2.25,p=.03), and greater ADA(t=3.2,p=.002). Finally both D and vagal bias were correlated with post-movie Rint (r=.43,p =.001;r=.39, p=.004). Conclusion: These findings suggest that insecure attachment may contribute to depression, stress vulnerability, and ANS dysregulation which potentiate pulmonary compromise in child asthma under stressful conditions.
The Metamorphosis of Medical Ethics
Authors: Edmund D. Pellegrino
Journal: JAMA (1993)

History is philosophy teaching by example. Dionysius of Halicarnassus When I entered medical school 50 years ago, medical ethics was, as it had been for centuries, solely the domain of the profession, protected from the mainstream of cultural change and framed in seemingly immutable moral precepts. This is the way medical ethics also appeared 30 years ago when I began to study, teach, and observe the field. If there was anything that seemed impervious to the metamorphosis we felt all of medicine to be undergoing, it was its ancient ethical framework. Today, that framework is under the severest strain in its long history. Medical ethics has become a subject of the widest public concern. Every one of its tenets is being seriously questioned and is likely to be reformulated. Under pressure of moral conflicts buffeting our entire culture, traditional moral supports have been weakened and precepts disassembled. Just what medical
The <b> <i>NOD2</i> </b> 3020insC Mutation and the Risk of Colorectal Cancer
Authors: Grzegorz Kurzawski, Janina Suchy, Józef Kładny, Ewa Grabowska, Marek Mierzejewski, Anna Jakubowska, Tadeusz Dȩbniak, Cezary Cybulski, Elsbieta Kowalska, Zbigniew Szych, Wenancjusz Domagała, Rodney J. Scott, Jan Lubiński
Journal: Cancer Research (2004)

Abstract Several predispositions to colorectal cancer have been identified, but little is known about genetic susceptibilities to disease in older persons. Colorectal cancer is a risk in Crohn’s disease and is believed to be associated with an inappropriate inflammatory response. Recently, the NOD2 gene has been associated with Crohn’s disease, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the NOD2 gene, which appear with significantly higher frequency in patients with the disease. One such mutation (3020insC) is believed to be clearly causative because it results in a prematurely truncated protein with a predicted reduction in functional efficiency. In this report, we have examined the frequency of the 3020insC mutation in a series of 856 individuals including 556 patients with colorectal cancer. The frequency of the 3020insC mutation in a consecutive series of 250 non-hereditary nonpolyposis colorectal cancer patients &amp;gt;50 years of age was significantly elevated compared with the control population (odds ratio, 2.23; P = 0.0046). The results indicate that NOD2 may be a predisposing factor to colorectal cancer characterized by an older average age of disease onset in persons who do not harbor any other genetic predisposition to disease.
Is continuous ambulatory peritoneal dialysis adequate long-term therapy for end-stage renal disease? A critical assessment.
Authors: J A Diaz-Buxo
Journal: Journal of the American Society of Nephrology (1992)

The significant growth in the continuous ambulatory peritoneal dialysis (CAPD) population and the recent interest in the quantitation of dialysis delivered have stimulated much work in the field of kinetic modeling, correlation between model parameters and clinical outcome, and comparison between the long-term benefits of hemodialysis and peritoneal dialysis. A critical assessment of the long-term results of CAPD therapy is made on the basis of clinical results and recent experience with kinetic models including urea and creatinine. The significant differences between the hemodialysis and CAPD techniques have generated hypotheses to allow comparison between the two groups using similar kinetic models. Although CAPD has proven beneficial in the initial treatment of large numbers of patients with ESRD, there is concern about the adequacy of CAPD as long-term therapy for many patients. Prospective, long-term studies applying solute kinetic modeling are necessary to establish the adequacy of CAPD.
Dominant negative retinoic acid receptor initiates tumor formation in mice
Authors: Tara S Kupumbati, Giorgio Cattoretti, Christine Marzan, Eduardo F Farias, Reshma Taneja, Rafael Mira-y-Lopez
Journal: Molecular Cancer (2006)

Abstract Background Retinoic acid suppresses cell growth and promotes cell differentiation, and pharmacological retinoic acid receptor (RAR) activation is anti-tumorigenic. This begs the question of whether chronic physiological RAR activation by endogenous retinoids is likewise anti-tumorigenic. Results To address this question, we generated transgenic mice in which expression of a ligand binding defective dominant negative RARα (RARαG303E) was under the control of the mouse mammary tumor virus (MMTV) promoter. The transgene was expressed in the lymphoid compartment and in the mammary epithelium. Observation of aging mice revealed that transgenic mice, unlike their wild type littermates, developed B cell lymphomas at high penetrance, with a median latency of 40 weeks. MMTV-RARαG303E lymphomas were high grade Pax-5+, surface H+L Ig negative, CD69+ and BCL6- and cytologically and phenotypically resembled human adult high grade (Burkitt's or lymphoblastic) lymphomas. We postulated that mammary tumors might arise after a long latency period as seen in other transgenic models of breast cancer. We tested this idea by transplanting transgenic epithelium into the cleared fat pads of wild type hosts, thus bypassing lymphomagenesis. At 17 months post-transplantation, a metastatic mammary adenocarcinoma developed in one of four transplanted glands whereas no tumors developed in sixteen of sixteen endogenous glands with wild type epithelium. Conclusion These findings suggest that physiological RAR activity may normally suppress B lymphocyte and mammary epithelial cell growth and that global RAR inactivation is sufficient to initiate a stochastic process of tumor development requiring multiple transforming events. Our work makes available to the research community a new animal resource that should prove useful as an experimental model of aggressive sporadic lymphoma in immunologically uncompromised hosts. We anticipate that it may also prove useful as a model of breast cancer.
A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis
Authors: A. P. Ralph, M. Ardian, A. Wiguna, G. P. Maguire, N. G. Becker, G. Drogumuller, M. J. Wilks, G. Waramori, E. Tjitra, None Sandjaja, E. Kenagalem, G. J. Pontororing, N. M. Anstey, P. M. Kelly
Journal: Thorax (2010)

Background The grading of radiological severity in clinical trials in tuberculosis (TB) remains unstandardised. The aim of this study was to generate and validate a numerical score for grading chest x-ray (CXR) severity and predicting response to treatment in adults with smear-positive pulmonary TB. Methods At a TB clinic in Papua, Indonesia, serial CXRs were performed at diagnosis, 2 and 6 months in 115 adults with smear-positive pulmonary TB. Radiographic findings predictive of 2-month sputum microscopy status were used to generate a score. The validity of the score was then assessed in a second data set of 139 comparable adults with TB, recruited 4 years later at the same site. Relationships between the CXR score and other measures of TB severity were examined. Results The estimated proportion of lung affected and presence of cavitation, but not cavity size or other radiological findings, significantly predicted outcome and were combined to derive a score given by percentage of lung affected plus 40 if cavitation was present. As well as predicting 2-month outcome, scores were significantly associated with sputum smear grade at diagnosis (p<0.001), body mass index, lung function, haemoglobin, exercise tolerance and quality of life (p<0.02 for each). In the validation data set, baseline CXR score predicted 2-month smear status significantly more accurately than did the proportion of lung affected alone. In both data sets, CXR scores decreased over time (p<0.001). Conclusion This simple, validated method for grading CXR severity in adults with smear-positive pulmonary TB correlates with baseline clinical and microbiological severity and response to treatment, and is suitable for use in clinical trials.
Synthesis of oxytocin in amnion, chorion, and decidua may influence the timing of human parturition.
Authors: R Chibbar, F D Miller, B F Mitchell
Journal: Journal of Clinical Investigation (1993)

Despite the widespread clinical use of oxytocin (OT) as a potent and specific stimulant of labor, previous research data have not supported a role for OT in the physiology of normal human parturition. We have demonstrated synthesis of OT mRNA in amnion, chorion, and decidua using Northern blot analysis, ribonuclease protection assays, and in situ hybridization. Probes directed towards both the 3' and 5' ends of the gene have been used. Levels were highest in decidua with considerably less in chorion and amnion and very low levels in placenta. The transcript size in decidua appears to be 60-80 nucleotides smaller than the transcripts in amnion and chorion. OT gene expression in chorio-decidual tissues increased three- to fourfold around the time of labor onset. Estradiol stimulated synthesis of OT mRNA during in vitro incubation. These results support the hypothesis of a paracrine system involving OT and sex steroids within intrauterine tissues wherein significant changes could occur without being reflected in the maternal circulation. Such a paracrine system could rationalize a long-sought role for oxytocin in the physiology of human labor. These data may lead to novel approaches towards prevention or treatment or preterm labor.
Proportional positive airway pressure: a new concept to treat obstructive sleep apnoea
Authors: J. Juhász, H. Becker, W. Cassel, S. Rostig, J‐H. Peter
Journal: European Respiratory Journal (2001)

Proportional positive airway pressure (PPAP) was designed to optimize airway pressure for the therapy of obstructive sleep apnoea (OSA). In a randomized crossover prospective study, the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure (CPAP) was evaluated. Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a random order. Obstructive and mixed respiratory events could be completely abolished with both forms of treatment. This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration (8.45±2.42 cmH 2 O) compared to CPAP (9.96±2.7 cmH 2 O) (p=0.002). The mean minimal arterial oxygen saturation ( S a,O 2 ) (82.8±6.5%) on the diagnostic night increased significantly (p&lt;0.001) to an average S a,O 2 of 93.35±1.71% and 93.19±2.9% during CPAP and PPAP titration. Total sleep time, slow wave sleep and rapid eye movement (REM) sleep increased significantly by the same amount during both CPAP and PPAP titration (p&lt;0.001), while sleep stage nonrapid eye movement (NREM) 1 and 2 decreased. Six patients preferred the PPAP titration night, four patients did not have a preference, and two patients preferred CPAP. The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep. The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure. Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea.
Brivanib for Hepatocellular Carcinoma Trials: Selection Bias From Barcelona Clinic Liver Cancer Stage?
Authors: Xingshun Qi, Jia Jia, Daiming Fan, Guohong Han
Journal: Journal of Clinical Oncology (2014)

Nowadays, the position of sorafenib in thetreatmentofadvancedhepatocellularcarcinoma(HCC)isfrequentlychallengedbyothermoleculartargetedagents.However,regardlessofwhether they are considered as ﬁrst-line or second-line treatmentoptions,allcompletedphaseIIIrandomizedcontrolledtrials(RCTs)reportnegativeresults.Similarly,twophaseIIIRCTs(ComparisonofBrivanibandBestSupportiveCaretoPlacebo BestSupportiveCarein Subjects With Advanced Hepatocellular Cancer Who Have Failedor Are Intolerant to Sorafenib Treatment [BRISK-PS] and A Ran-domized, Double-Blind, Multi-Center Phase III Study of BrivanibVersusSorafenibAsFirst-LineTreatmentinPatientsWithAdvancedHepatocellularCarcinoma[BRISK-FL])thatwererecentlypublishedin
Autonomic dysfunction in gastrointestinal motility disorders.
Authors: A E Bharucha, M Camilleri, P A Low, A R Zinsmeister
Journal: Gut (1993)

The records of 113 consecutive patients with a suspected gastrointestinal motility disorder referred between January 1988 and July 1991 were retrospectively reviewed. The aims were to identify the prevalence of autonomic dysfunction in those with or without associated neurological disease and to determine the diagnostic value of testing for autonomic dysfunction. All patients had gastrointestinal manometry (3 hours fasting, 2 hours fed), 94 of 113 underwent testing of sympathetic adrenergic and cholinergic function and cardiovagal cholinergic function. All tests were scored in a standard manner. There was a significant (p &lt; 0.05) but modest (r = 0.28) rank correlation between autonomic and motility scores. This correlation was stronger (r = 0.67, p = 0.01) in diabetic patients. The number of patients in each group with autonomic dysfunction was as follows: irritable bowel syndrome nine of 33, idiopathic upper gastrointestinal dysmotility six of 21, diabetes mellitus nine of 13, identified non-diabetic neurological syndromes six of nine, postvagotomy or abdominal surgery three of 11, and myopathic pseudo-obstruction two of seven. Autonomic testing is useful in the assessment of autonomic involvement outside the gastrointestinal tract. Logistic discriminant analysis showed that autonomic function testing did not add to the diagnostic value of motility tests in distinguishing between patients with and without irritable bowel syndrome, although a slight improvement was indicated for identifying neuropathic dysmotilities. Thus, the aetiological role of general autonomic dysfunction in irritable bowel syndrome and idiopathic and postvagotomy dysmotilities deserves further study. The addition of autonomic function tests does not add substantially to the diagnostic accuracy of clinical, radiological, endoscopic, and manometric techniques in most patients referred for evaluation of a suspected motility disorder.
Partial inhibition of nitric oxide synthesis in vivo does not inhibit glucose production in man
Authors: Fleur Sprangers, Wilbert T. Jellema, Christa E. Lopuha[auml ], Erik Endert, Mari[euml ]tte T. Ackermans, Johannes J. van Lieshout, Jaring S. van der Zee, Johannes A. Romijn, Hans P. Sauerwein
Journal: Metabolism (2002)
MDM2 Overexpression Deregulates the Transcriptional Control of RB/E2F Leading to DNA Methyltransferase 3A Overexpression in Lung Cancer
Authors: Yen-An Tang, Ruo-Kai Lin, Yo-Ting Tsai, Han-Shui Hsu, Yi-Chieh Yang, Chih-Yi Chen, Yi-Ching Wang
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Overexpression of DNA 5′-cytosine-methyltransferase 3A (DNMT3A), which silences genes including tumor suppressor genes (TSG), is involved in many cancers. Therefore, we examined whether the transcriptional deregulation of RB/MDM2 pathway was responsible for DNMT3A overexpression and analyzed the therapeutic potential of MDM2 antagonist for reversing aberrant DNA methylation status in lung cancer. Experimental Design: The regulation of DNMT3A expression and TSG methylation status by RB/MDM2 was assessed in cancer cell lines and patients. The effects of Nutlin-3, an MDM2 antagonist, on tumor growth in relation to DNMT3A expression and TSG methylation status were examined by xenograft model. Results: We found that RB suppressed DNMT3A promoter activity and mRNA/protein expression through binding with E2F1 protein to the DNMT3A promoter, leading to the decrease of methylation level globally and TSG specifically. In addition, MDM2 dramatically induced DNMT3A expression by negative control over RB. In clinical study, MDM2 overexpression inversely correlated with RB expression, while positively associating with overexpression of DNMT3A in samples from patients with lung cancer. Patients with high MDM2 and low RB expression showed DNMT3A overexpression with promoter hypermethylation in TSGs. Treatment with Nutlin-3, an MDM2 antagonist, significantly suppressed tumor growth and reduced DNA methylation level of TSGs through downregulation of DNMT3A expression in xenograft studies. Conclusions: This study provides the first cell, animal, and clinical evidence that DNMT3A is transcriptionally repressed, in part, by RB/E2F pathway and that the repression could be attenuated by MDM2 overexpression. MDM2 is a potent target for anticancer therapy to reverse aberrant epigenetic status in cancers. Clin Cancer Res; 18(16); 4325–33. ©2012 AACR.
Prognostic Judgments of Gastroenterologists, Medical Students, and College Undergraduates
Authors: David J. King
Journal: JAMA (1966)

Twenty gastroenterologists, medical students, and college undergraduates placed 20 case histories of Laennec's cirrhosis in rank order in terms of favorability of immediate prognosis. From these data, three sets of prognostic scale scores were computed. There was a marked similarity between the prognostic scale scores of the medical students and college undergraduates on patients with a favorable prognosis (relative to the judgments of the gastroenterologists). The prognostic scale scores of the medical students agreed much more clearly with those of the gastroenterologists, as contrasted with the college undergraduates, in cases of poor prognosis. The implications for research of this nature were discussed.
Serum Insulin-like Growth Factor-I Level Is an Independent Predictor of Recurrence and Survival in Early Hepatocellular Carcinoma: A Prospective Cohort Study
Authors: Eun Ju Cho, Jeong-Hoon Lee, Jeong-Ju Yoo, Won-Mook Choi, Min Jong Lee, Yuri Cho, Dong Hyeon Lee, Yun Bin Lee, Jung Hee Kwon, Su Jong Yu, Jeong Min Lee, Kyung-Suk Suh, Kion Kim, Yoon Jun Kim, Jung-Hwan Yoon, Chung Yong Kim, Hyo-Suk Lee
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment. Experimental Design: Consecutive patients with hepatocellular carcinoma who had undergone surgical resection, radiofrequency ablation, or percutaneous ethanol injection as curative treatments of early hepatocellular carcinoma were included from two prospective cohorts and the training set (n = 101) and the validation set (n = 91) were established. Serum samples were collected before treatment and the levels of IGF-I and IGF-binding protein-3 (IGFBP-3) were analyzed with regard to their associations with recurrence and survival. Results: In the training set, patients with low IGF-I levels showed significantly shorter TTR [median, 14.6 months; 95% confidence interval (CI), 1.8–27.5] than patients with high IGF-I levels (median, 50.8 months; 95% CI, 36.9–64.7; P &amp;lt; 0.001) during a median follow-up period of 52.4 months. In the multivariate analysis, low levels of IGF-I were an independent predictor of recurrence (HR, 2.49; 95% CI, 1.52–4.08; P &amp;lt; 0.001). Furthermore, together with high-serum α-fetoprotein and multiple tumors, low levels of IGF-I remained an independent predictor of poorer survival (HR, 8.00; 95% CI, 1.94–33.01; P = 0.004). Applied to the independent validation set, low-serum IGF-I levels maintained their prognostic value for shorter TTR and OS. Conclusions: Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment. Clin Cancer Res; 19(15); 4218–27. ©2013 AACR.
Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer
Authors: Elizabeth L. Kaufman, Judith S. Jacobson, Dawn L. Hershman, Manisha Desai, Alfred I. Neugut
Journal: Journal of Clinical Oncology (2008)

Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk.We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC >or= 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC.Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC.PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.