tbuckley/cabot-search huggingface dataset:
Pharmacokinetic studies of quinidine in patients with arrhythmias.
Authors: K A Conrad, B L Molk, C A Chidsey
Journal: Circulation (1977)

The absorption and disposition of quinidine were measured in nine patients following single oral and intravenous dosing. A new specific chromatographic method was used to measure the drug in plasma and urine. After intravenous administration, the plasma half-life (t1/2beta) was 7.8+/-0.7 h, the volume of distribution (Vd) was 3.0+/-0.5 liters/kg, and the total body clearance was 4.8+/-0.8 ml/min/kg. After oral administration, 87+/-7% (mean+/-SEM) was available to the systemic circulation. Quinidine was removed primarily by hepatic metabolism, with the renal clearance averaging only 1.0+/-0.2 ml/min/kg. Mean quinidine concentrations were estimated in 42 patients on chronic therapy by averaging blood levels during a dosing interval. In patients without heart failure, these corresponded well to mean drug levels predicted from the pharmacokinetic parameters measured after a single intravenous dose, but in patients with heart failure, the values for mean quinidine concentrations were higher than predicted. This suggests that impaired elimination of the drug or a decreased volume of its distribution, or both, may develop in heart failure.
Abstract P223: Dietary Magnesium and the Risk of Stroke among Women
Authors: Sally N Akarolo-Anthony, Kathryn M Rexrode, Donna Spiegelman, Walter C Willett
Journal: Circulation (2014)

Background: Epidemiology studies suggest that high magnesium intake may decrease the risk of stroke by reducing hypertension, endothelial dysfunction and carotid artery thickness, but the results are inconsistent. We therefore examined the association between magnesium intake and stroke type in a cohort with repeated measurement of diet, long duration of follow up, and a large sample size. Methods: We prospectively followed 86,149 women in the Nurses’ Health Study, aged 35 to 55 years, who were free of diagnosed cardiovascular disease and cancer at baseline in 1980. Data on dietary intake were collected with a semi-quantitative food frequency questionnaire at baseline in 1980, 1984, 1986 and then every 4 years, while data on stroke, stroke risk factors and potential confounders were collected at baseline and updated biennially. Strokes were classified according to the National Survey of Stroke criteria; and strokes for which medical records were not available were classified as probable/unknown. We calculated the hazard ratio (95% CI) of stroke by quintiles of magnesium intake, using multivariate Cox proportional hazard models, adjusting for potential confounders. Results: During 28 years of follow-up, 3237 total strokes (1664 ischemic, 544 hemorrhagic and 1029 probable/unknown) were documented. In multivariate analyses adjusting for age, total calories, smoking, body-mass index, parental history of heart disease, alcohol intake, physical activity, menopausal therapy, history of hypertension, hypercholesterolemia and diabetes at baseline, as well as use of multivitamin, aspirin, and thiazides, women in the highest quintile of magnesium intake had a relative risk (RR) of 0.85 (95% CI, 0.72 to 0.96; P for trend=0.03) for total stroke; 0.86 (95% CI, 0.72 to 1.01; P for trend=0.05) for ischemic stroke; and 0.85 (95% CI, 0.62 to 1.08; P for trend=0.37) for hemorrhagic stroke, compared with those in the lowest quintile. Further adjustment for potassium and calcium attenuated these associations; for total stroke the risk estimate was 0.90 (0.75 to 1.06; P for trend=0.38). Conclusions: Low magnesium intake may contribute to higher risk of stroke, but distinction from potential effects of potassium and calcium is difficult.
Long-term reproducibility of exhaled nitric oxide and exhaled breath temperature in healthy children
Authors: Francesca Ruggeri, Mario Barreto, Lorenza Chiossi, Carlotta Bianchini, Ilaria Caiazzo, Maria Chiara Supino, Susy Martella, Maria Pia Villa
Journal: European Respiratory Journal (2013)

Background  Measurements of the fractional concentration of exhaled nitric oxide (FE NO ) and exhaled breath temperature (EBT) are easy to perform, non-invasive and considered reproducible at short-term; data on their long term reproducibility is needed.  Aims  To assess reproducibility of FE NO  and EBT in healthy children one-year apart and their relationship with lung function and anthropometric changes.  Methods  In 41 healthy children (24 males) aged 9.8±1.6 yr, range 8.0-13.8, we obtained duplicated measurements of FE NO  and EBT in two sessions one-year apart (2011 and 2012). Subjects did also spirometry in both sessions. The intraclass coefficient correlation (ICC) and the coefficient of repeatability (CR=2 SD) were assessed. Overtime changes in variables (“D” prefix) were calculated.  Results  Intra-session reproducibility of duplicate measurements was high in both sessions [(ICC >0.94 for both FE NO  and EBT); (CR: FE NO  5.2 ppb and 3.0 ppb, EBT 1.8 and 1.2 °C)]. Geometric means (95% confidence interval) did not change significantly from the 2011 to the 2012 sessions [FE NO : 10.6 (9.3-12.2) ppb and 10.2 (9.2-11.3) ppb; EBT: 32 (31.3-32.7) °C and 32.6 (31.9-33.2) °C]. Reproducibility decreased after 1 year [FE NO  (ICC: 0.48, CR: 11.0 ppb); EBT (ICC: 0.75, CR: 3.5 °C)]. The between-year percent increase in FE NO  correlated with decreased lung function (DFEV 1 % r=-0.33, DFEF 25-75  % r=-0.39, p  Conclusion  Reproducibility of both FE NO  and EBT decreases after one year in healthy children; their changes have a different meaning; FE NO  is more affected by changes in bronchial patency whereas EBT by increases in body mass index.
Changes in pathological narcissism
Authors: E Ronningstam, J Gunderson, M Lyons
Journal: American Journal of Psychiatry (1995)

This study investigated types of change that occur over time in the psychopathology of narcissistic patients.Baseline scores on the Diagnostic Interview for Narcissism of 20 patients, clinically diagnosed as having narcissistic personality disorder, were contrasted with their scores 3 years later by means of t tests and chi-square statistics. The authors then compared these changes in narcissism with the patients' accounts of their life events during the interval between the two assessments.A significant decrease in the overall level of pathological narcissism was found, particularly in the areas of interpersonal relations and reactiveness. At follow-up, 60% of the subjects had reached the cutoff score on the diagnostic interview that indicated significant improvement, and 40% remained unchanged, with a high level of pathological narcissism. A high baseline level of narcissism in interpersonal relations was associated with absence of change at follow-up. Examination of life events in the interval between assessments suggests that changes in pathological narcissism are related to three kinds of experiences: achievements, new durable relationships, and disillusionments.The instability of narcissistic psychopathology found in this study raises questions about the construct validity of narcissistic personality disorder as a diagnostic category and about the core construct of pathological narcissism.
Meta-analysis and the meta-epidemiology of clinical research
Authors: D. Julian, J. Le Lorier, G. Gregoire
Journal: BMJ (1998)

AIM: To test the hypothesis that sudden infant death syndrome (SIDS) may be caused by toxins of commonly occurring bacteria in infants lacking developed immunity. METHODS: Nasopharyngeal microbial isolates from 22 pairs of SIDS cases and healthy infants matched for age (by month), sex, and sampling time (by month) were compared for lethal toxigenicity. Crude toxin preparations were made from isolates cultured on dialysis membrane overlaid on agar, and these preparations were then tested for lethality by intravenous injection into 11 day old chick embryos. RESULTS: Fifteen (68%) of the SIDS cases were each found to have at least one lethally toxigenic organism in their nasopharyngeal flora; only eight (36%) of the flora of normal infants included a lethally toxigenic species. CONCLUSION: Infants who have died of SIDS have a significantly higher (p less than 0.05) probability than matched healthy infants of having a lethally toxigenic bacterial species in their nasopharyngeal flora.
Abstract 37: Calibration of APACHE II Score to Predict Mortality in Out-of-Hospital and In-Hospital Cardiac Arrest
Authors: Michael W Donnino, Justin D Salciccioli, Andre Dejam, Caitlin Jones-Bamman, Brandon Giberson, Michael N Cocchi
Journal: Circulation (2011)

Introduction: Severity of illness scores can predict outcomes in critically ill patients. However, the calibration of previously established scores in post-cardiac arrest is poorly established. Objective: To assess the calibration of the Acute Physiology and Chronic Health Evaluation (APACHE II) score in out-of-hospital and in-hospital cardiac arrest. Methods: A prospective observational study of adult cardiac arrest at an urban tertiary care hospital during the period from 12/2007 to 12/2010. Inclusion criteria: 1. Adult (&gt;18 years); 2. OHCA; 3. Return of spontaneous circulation (RSOC). Traumatic cardiac arrests were excluded. We recorded baseline demographics, arrest event characteristics, follow-up vitals and laboratory data, and in-hospital mortality. APACHE II scores were calculated at the time of ROSC, and at 24hrs, 48hrs, and 72hrs. We used simple descriptive statistics to describe the study population. Univariate logistic regression was used to predict mortality with APACHE II as a continuous predictor variable. Discrimination of APACHE II scores was assessed using the area under the curve (AUC) of the receiver operator characteristic (ROC) curve. Results: A total of 229 patients were analyzed. The median age was 70 years (IQR: 56 - 79) and 32% were female. APACHE II score was a significant predictor of mortality for both OHCA and IHCA at baseline and at all follow-up time points (all p &lt; 0.01). Discrimination of the score increased over time and achieved very good discrimination after 24hrs (Table 1). Conclusion: The ability of APACHE II score to predict mortality improves over time in the 72-hours following cardiac arrest. These data suggest that after 24-hours, APACHE II scoring is a useful severity of illness score in all post-cardiac arrest patients.
MCT-1 oncogene promotes tumor growth by up-regulation of EGFR signaling pathway
Authors: Kasiappan Ravi, Hung-Ju Shih, Chik-On Choy, Kang-Lin chu, Chung-Li Shu, Hsin-Ling Hsu
Journal: Clinical Cancer Research (2007)

C35   MCT-1 (Multiple copies in T-cell malignancy) is an oncogene initially identified in human T-cell lymphoma. MCT-1 has been shown to decrease cell-doubling time, shorten the duration of G1 phase, and increased cyclin D1 and CDK-4 activities. Overexpression of MCT-1 oncoprotein induces cellular transformation, and deregulates the DNA damage-signaling cascade and checkpoint controls that lead to genome instability. Here, we demonstrate that MCT-1 oncogene enhances cell survival and proliferation through EGFR signaling pathway and promotes tumorigenicity in mammals. Forced expression of MCT-1 elevates EGFR, HER-2 and H-Ras levels in association with activated AKT and MAPK phosphorylation. Besides, EGFR, HER-2 and H-Ras mRNA expression attitudes are also higher in MCT-1 overexpressing cells than control cells. Furthermore, the phosphor-activated MAPK is remarkably increased in p53 deficient MCT-1 oncogenic cells. Interestingly, ectopic MCT-1 promotes tumor growth of BALB/c nude mice xenografting with p53 deficient (H1299) or K-Ras mutant (A549) cells. MCT-1 gene expression is significantly increased in MCT-1 xenograft tumors than that of control cells developed tumors and normal tissues. Hemoglobin contents, an index of tumor vascularization and angiogenesis that is vital for tumor growth and metastasis, is dramatically increased in MCT-1 xenograft tumors. Boyden chamber migration assay further reveals that ectopic expression of MCT-1 increases cell migration ability as compared with control cells. Hence, our data indicate that MCT-1 oncoprotein activates EGFR signaling pathway and it’s downstream. Those are essential for cell proliferation, survival and migration. The further in-depth studies are defensible to prove MCT-1 tumorigenic impacts and this will greatly help for identifying drug-able targets.
Symptoms of eating disorders in patients with obsessive-compulsive disorder
Authors: T A Pigott, M Altemus, C S Rubenstein, J L Hill, K Bihari, F L'Heureux, S Bernstein, D L Murphy
Journal: American Journal of Psychiatry (1991)

This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders.The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory.The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive-compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects.These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders.
Lysophosphatidic acid/vascular endothelial growth factor autocrine loop regulates ovarian cancer telomerase
Authors: Yira Bermudez, Hua Yang, Beatriz O. Saunders, Jin Q. Cheng, Santo V. Nicosia, Patricia A. Kruk
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4996 

Telomerase, a ribonucleoprotein expressed in over 90% of all cancers, including ovarian cancer, plays an important role in cellular immortalization, survival and drug resistance. Although telomerase regulation is complex, many growth factors, including vascular endothelial growth factor (VEGF) can regulate telomerase activity in non-ovarian cancer models. Likewise, ovarian tumor growth and metastasis require VEGF-dependent angiogenesis. Since VEGF secretion by cancer cells functions in an autocrine loop to promote cancer cell growth and survival, this study examined the contribution of VEGF to regulate telomerase in ovarian cancer cells. We found that ovarian cancer cells, but not normal ovarian surface epithelial (OSE) cells, stimulated endothelial angiogenic properties, secreted in excess of 1000 pg/ml of VEGF165 and possessed the VEGF receptors, VEGFR-1 and VEGFR-2. VEGF165 also elevated telomerase activity in cancer cells, but was ineffective in telomerase-negative OSE cells. Inhibition of VEGF expression with either neutralizing antibodies or preventing VEGF receptor activation suppressed VEGF-mediated telomerase activity. VEGF increased telomerase hTERT transcription via the MAPK ERK1/2 pathway and targeted transcription binding sequences within the 976- to 578-bp regions of the hTERT promoter. Further, the potential ovarian cancer biomarker and upstream regulator of VEGF, lysophosphatidic acid (LPA), increased VEGF production and telomerase activity in all ovarian cancer cell lines examined. In addition, LPA-induced telomerase activity was abolished by concurrent treatment with the VEGF receptor inhibitor, CBO-P11, indicating that LPA-mediated telomerase activity was VEGF-dependent. In conclusion, these data represent a paradigm shift in our previously held views of VEGF solely as a regulator of endothelial cell growth and survival and identify telomerase as a novel, molecular target of LPA. Clinical modulation of the LPA/VEGF autocrine loop, then, could target and reduce telomerase activity leading to improved chemosensitivity in ovarian cancer, the leading cause of gynecological death in the US.
Stages of onset of schizophrenic psychosis
Authors: John P. Docherty, Daniel P. Van Kammen, Samuel G. Siris, Stephen R. Marder
Journal: American Journal of Psychiatry (1978)

On the basis of a review of the literature describing the process of schizophrenic illness, the authors conclude that schizophrenic psychosis is one stage in a process of psychological and biological breakdown that has a specific structure and a characteristic unfolding consisting of the sequential appearance of hierarchically ordered, distinguishable, and recognizable psychological states. They present on illustrative case history of a patient who was able to describe her feelings during the process of decompensation to schizophrenic psychosis and two case histories of patients whose decompensations were rated according to the authors' State of Illness Rating Scale.
Matrilysin Contributes to Bronchiolization of Alveoli, a Potential Pre-malignant Lesion of Lung Cancer
Authors: Xiaoyang Wang, Heungnam Kim, Sandra Jensen-Taubman, El Habib Dakir, Ilona R. Linnoila
Journal: Cancer Research (2006)

4370  Bronchiolization of alveoli (BOA) is a histologically distinct lesion, which occurs in a variety of pathologic conditions, including inflammation, chemical irritation and exposure to carcinogens. Up to 12% of lung cancer resection specimens contain BOA suggesting that it is a pre-malignant lesion (Jensen et al., Int. J. Cancer: 1998, 75, 489–496) . In the current study we used a previously characterized transgenic (TG) mouse model (Wang et al., Proc. AACR : 2004, Vol.45) to study the mechanism of BOA. We show that both human and TG mouse BOA lesions express markers of airway epithelial cells including Clara cell specific protein CC10, ciliated cell marker β-tubulin, keratins 8 and 18 but are negative for alveolar type II cell marker SP-C, suggesting that BOA is derived from bronchiolar cells. Moreover, TG mouse BOA revealed high levels of matrilysin (matrix metalloprotein 7; MMP-7) mRNA and protein, which is frequently expressed by migrating cells and precancerous lesions. Matrilysin was absent in wild type airway epithelium. We also detected matrilysin immunoreactivity in human lungs: in 8 out of 8 cancers, 5 out of 20 BOAs while adjacent normal airway revealed minimal reactivity. To further investigate the function of matrilysin in BOA we transfected the full length cDNA gene into immortalized human bronchial and bronchiolar epithelial cells (BEAS-2B and HPL1D, respectively). The level of matrilysin, which is a secretory MMP, increased markedly in the culture media of the transfected BEAS-2B (5.6 fold) and HPL1D (2.3 fold) cells compared to controls when analyzed by ELISA assay. Both transfected cell lines also revealed increased cell growth after 3 days. In order to examine if matrilysin facilitates invasion, BEAS-2B and HPL1D cells were treated by various concentrations of active recombinant human matrilysin (1μM, 5 μM and 25 μM) which resulted in increasing invasion indices. We conclude that BOA is composed of bronchiolar type cells which may acquire a premalignant phenotype of increased growth and invasion through expression of matrilysin.
Cancer in the offspring of radiation workers
Authors: F. Alexander, C. Busby, M. S. Cato, A. Stewart, G J Draper, M P Little, T Sorahan, L J Kinlen
Journal: BMJ (1998)

Editor—The results of the study of Draper et al showing an association between worker status of parents and leukaemia in children1 are unlikely to be attributable to chance. Some exposure to a causative agent, either at the workplace of male radiation workers or in the communities to which they belong, must increase the risk of childhood leukaemia. 

Draper et al suggest an oncogenic infectious agent that results from high rates of population mixing as the cause of increased leukaemia risk. Their evidence is based on three factors: an association of population mixing with childhood leukaemia; population mixing in the vicinity of certain nuclear sites; and worker migration between sites. These factors do not explain the excess risk of 80%. A review of all the studies published at that time of childhood leukaemia in areas with high population mixing2 gave 50% as best estimate of increased risk, with only one having an estimate as high as 80%. 

The effects of population mixing, however, may be diluted in these workers for several reasons. Firstly, only a proportion will have been employed at establishments such as Sellafield. Secondly, the time windows of documented excess mixing near these plants are mostly short relative to the 34 years of this study. Thirdly, radiation worker status of the father before conception of the child is, here, an inaccurate measure of the relevant exposure (which presumably occurs after conception). Nevertheless, given the accumulating evidence that links patterns of exposure to infectious agents with childhood leukaemia,2,3 an infectious origin for this excess should be considered. 

So, I suggest, should a connection with radiation. Maybe an additional factor that applies to communities of radiation workers has the same effect as population mixing—that is, to favour microepidemics of the putative agent. The possible relevance of immunotoxic properties of ionising radiation in individual people has been proposed.4 The community effect on herd immunity can be much larger than the sum of small individual parts5 and could apply here. Immunosuppression of a human population would increase the risk of microepidemics by increasing the probability of infection after a single contact. In addition, for agents that establish latency it would increase the number of infectious people. Mild immunosuppression of the population may be another mechanism in communities that increases the risk of childhood leukaemia. 

Case and control fathers1 should now be linked to National Registry of Radiation Workers records to determine radiation worker status after conception. Also linked, if possible, should be examination of contact between the fathers (employment at the same site at the same time), especially at critical periods such as gestation, the first year of life, and the year preceding diagnosis.
Baroreflex Activation Therapy Lowers Blood Pressure in Patients With Resistant Hypertension
Authors: John D. Bisognano, George Bakris, Mitra K. Nadim, Luis Sanchez, Abraham A. Kroon, Jill Schafer, Peter W. de Leeuw, Domenic A. Sica
Journal: Journal of the American College of Cardiology (2011)