tbuckley/cabot-search huggingface dataset:
Imipramine and Enuresis
Authors: Gilbert I. Martin
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Great speculation concerning imipramine's mechanism of action in enuresis continues. Some describe augmentation of internal urethral sphincter tone as the primary effect.<sup>1</sup>Studies of micturition and sleep patterns during continuous monitoring<sup>2</sup>of intravesical pressure describe the following: Increase in bladder pressure during sleep stages III and IV. Increase in uninhibited spontaneous bladder contractions in sleep stages III and IV. Decrease in contractions and low intravesical pressure in REM sleep and in NREM sleep stages I and II. A unifying hypothesis suggests a fundamental defect in enuretic children in subcortical centers controlling micturition, in maturation of neural pathways, and in the level of sleep. Initiation of the enuretic episode from stage IV sleep suggests the loss of voluntary control over micturition, possibly due to generalized cortical depression.<sup>3</sup>The greater frequency of spontaneous bladder contractions in both infants and enuretic children suggests a
Treatment implication from the potential association between nonalcoholic fatty liver disease and cardiovascular disease
Authors: Liang Shen
Journal: Hepatology (2011)

In recent years, the potential association between nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has attracted much interest,1 generating discussion that NAFLD patients should perhaps be treated not only for their liver disorder but also owing to their associated cardiovascular risk factors. However, it seems that at present we cannot draw a definitive conclusion on the association between NAFLD and CVD. I read with great interest the article by Ghouri et al.,2 who reviewed data from recent prospective studies and concluded that a diagnosis of NAFLD is insufficient to consider patients as being at high risk for CVD. Nevertheless, it is interesting to note that Targher et al.3 recently reviewed the rapidly growing body of clinical evidence supporting a strong link between NAFLD and the CVD risk. Therefore, additional effort is encouraged to shed light on the link between the two disorders. I do not intend to judge the association between NAFLD and CVD; however, I sincerely hope the current debatable status will not hamper the research community to optimize the treatment strategy. Before drawing a definitive conclusion on the association between the two disorders, I submit that the NAFLD treatment strategy, which also possesses the potential to prevent/reduce the associated risk of CVD, may serve as a good approach for NAFLD patients. The advantage of this strategy is that if no or only a weak association between NAFLD and CVD is found, the approach will not bring additional burden to the patients. There have been numerous clinical trials of various treatment modalities for NAFLD as comprehensively reviewed by Lam and Younossi,4 including weight loss agents, insulin-sensitizing agents, lipid-lowering agents, antioxidants, probiotics, and other novel compounds. In addition, Satapathy and Sanyal5 recently discussed the status of current and emerging treatment strategies for nonalcoholic steatohepatitis patients and highlighted the great potential of antioxidant therapy. Because the treatment strategies for NAFLD and CVD are similar, it is promising to consider that one of the above-mentioned treatment modalities for NAFLD could also be applied for associated risk of CVD. Liang Shen Ph.D.*, * Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo, P. R. China.
Polybrominated biphenyl (PBB) in the growing pig diet
Authors: P. K. Ku, M. G. Hogberg, A. L. Trapp, P. S. Brady, E. R. Miller
Journal: Environmental Health Perspectives (1978)

Twelve pigs which averaged 13.7 kg were randomly allotted from litters to a corn-soybean meal grower diet containing 0, 20, or 200 ppm of polybrominated biphenyls (PPB). During a 16-week growth trial, average daily gain (kg), average daily feed (kg) and feed/gain for pigs on diets containing 0, 20, or 200 ppm of PBB, respectively, were 0.82, 2.45, 2.99; 0.67, 1.88, 2.79; 0.45, 1.23, 2.70. Mean daily gain differences between all lots were highly significant (p &lt; 0.01). Blood from each pig was withdrawn biweekly through the first 8 weeks of the trial and at 4 week intervals thereafter. Hemoglobin and hematocrit differed significantly only at the 6 weeks bleeding, being reduced in pigs receiving 200 ppm of PBB. Erythrocyte reduced glutathione concentration and glutathione peroxidase activity were not significantly influenced by level of dietary PBB. Serum lactic dehydrogenase activity was significantly higher in control pigs than in either PBB supplemented lots at 16 weeks. There was no significant influence of PBB upon serum glutamic oxaloacetic transaminase, serum alkaline phosphatase or serum creatine phosphokinase. Based on these enzyme assays, PBB produced no evidence of significant necrosis of liver, myocardium, or skeletal muscle. There was no consistent effect of dietary PBB upon total serum protein concentration or electrophoretic profile. Pigs on either level of PBB did not have overt clinical signs of toxicity during the 16-week test period with the exception of a dermatosis on the ventral surface of two of the pigs receiving 200 ppm of PBB. There was a marked increase in liver weight of pigs receiving either level of dietary PBB. Heart, kidney, and adrenals of pigs receiving either level of dietary PBB were heavier as a percent of body weight than that of control pigs. Fat retention of PBB and urinary and fecal PBB excretion were significantly affected by dietary PBB level. Grossly, the glandular portion of the stomach appeared somewhat hyperplastic in pigs on 200 ppm of PBB. Two pigs which had received 200 ppm of PBB were placed on the control diet and over the next 14 weeks normal growth rate occurred. One of these pigs was killed and organ weights were normal. The other pig, a gilt, came into estrus. She was bred and conceived. At the end of gestation, four pigs were born. Three survived and grew normally; the one death at birth examined at gross necropsy did not reveal changes in organ size or other tissue alterations.
Abstract 503: Mammary fibroblasts induce hormone-independent growth in estrogen receptor-positive breast cancer cells via an epithelial-to-mesenchymal transition in a 3D cell culture model.
Authors: Sarah E. Holton, Anna Bergamaschi, Benita S. Katzenellenbogen, Rohit Bhargava
Journal: Cancer Research (2013)

Abstract The majority of breast cancers diagnosed in the United States are estrogen receptor positive (ER+). These patients may respond to targeted endocrine therapies, but up to 30% of patients experience a cancer recurrence. We hypothesized that the molecular interaction of ER+ breast cancer cells with mammary fibroblasts might lead to endocrine resistance and, eventually, breast cancer relapse. We developed a three-dimensional (3D) co-culture model representing cancer cell-fibroblast interactions during early tumor invasion. We show that the proliferation of MCF7 ER+ cells switches from hormone-dependent to growth factor-dependent in the presence of human mammary fibroblasts. Further, we determine that this transition is associated with gene and protein hallmarks of the epithelial-mesenchymal transition (EMT) in tumor cells, in particular upregulation of SNAIL and SLUG mRNA and loss of E-Cadherin protein. We identified the secreted proteins that arise from epithelial-fibroblast interactions in this system using an antibody-based array. The proteins secreted into the conditioned medium are sufficient to induce EMT markers in primary normal human mammary epithelial cells (HMECs). Our report demonstrates that estrogen receptor activity is dynamic and therefore is not best assessed with immunohistochemical techniques alone. For the facile and rapid determination of ER activity in a clinical setting, we propose the use of an emerging imaging method, highly sensitive label-free Fourier Transform infrared (FT-IR) spectroscopic imaging. We validate this technology in predicting endocrine sensitivity in breast cancer here, by detecting significant changes in spectroscopic peaks correlated with proliferation and metabolism of MCF7 cells grown in 3D culture. (Supported by grants from The Breast Cancer Research Foundation to BSK, DOD postdoctoral fellowship W81XWH-09-1-0398 to AB, NIH NCI Alliance for Nanotechnology in Cancer ‘Midwest Cancer Nanotechnology Training Center R25 CA154015A to SEH, and National Institutes of Health RO1CA138882 to RB.) Citation Format: Sarah E. Holton, Anna Bergamaschi, Benita S. Katzenellenbogen, Rohit Bhargava. Mammary fibroblasts induce hormone-independent growth in estrogen receptor-positive breast cancer cells via an epithelial-to-mesenchymal transition in a 3D cell culture model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 503. doi:10.1158/1538-7445.AM2013-503
The treatment of Raynaud's phenomenon
Authors: PAULINE M. DOWD
Journal: British Journal of Dermatology (1986)

Journal Article The treatment of Raynaud's phenomenon Get access PAULINE M. DOWD PAULINE M. DOWD The Middlesex Hospital, Mortimer Street, London W1N 8AA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 114, Issue 5, 1 May 1986, Pages 527–533, https://doi.org/10.1111/j.1365-2133.1986.tb04059.x Published: 01 May 1986
Wildlife as sentinels of human health effects in the Great Lakes--St. Lawrence basin.
Authors: G A Fox
Journal: Environmental Health Perspectives (2001)

There is no existing formal, long-term program for gathering evidence of the incidence and severity of the health effects of toxic substances in wildlife. However, research-based studies of bald eagles, herring gulls, night herons, tree swallows, snapping turtles, mink, and beluga over the past 30 years have revealed a broad spectrum of health effects in the Great Lakes-St. Lawrence basin including thyroid and other endocrine disorders, metabolic diseases, altered immune function, reproductive impairment, developmental toxicity, genotoxicity, and cancer. These effects occurred most often and were most severe in the most contaminated sites (Green Bay, Saginaw Bay, Lake Ontario, the St. Lawrence estuary, and more recently, Lake Erie), some of which are International Joint Commission-designated Areas of Concern (AOCs). In all cases, a strong argument can be made for an environmental etiology, and in many cases for the involvement of persistent organic pollutants, particularly polychlorinated biphenyls, polychlorinated dibenzo-(italic)p(/italic)-dioxins, and polycyclic aromatic hydrocarbons. For some, the association with particular contaminants is consistent with controlled studies, and in some, dose-response relationships were documented. The biologic significance of these health impairments to the affected species is currently unclear, but they resemble those observed with increased incidence in human subpopulations in one or more AOCs. Formalizing health effects monitoring of sentinel wildlife species by the parties to the Canada-USA Great Lakes Water Quality Agreement is required. This would facilitate the optimal use of sentinel wildlife health data in a larger, epidemiologic weight-of-evidence context upon which to base decisions and policies regarding the effects of chemical exposures on human populations.
Medical errors: a common problem
Authors: K G M M Alberti
Journal: BMJ (2001)

Papers p 517 Letters p 548 Reviews pp 562, 563 

Medical errors continue to dominate newspaper headlines. There is rarely an informed comment on likelihood or cause, rather a tacit assumption that they should never happen—and an implicit conclusion that they are getting more common. What is the truth? Firstly, errors have always happened. Secondly, there has been no clear indication as to how common they are in the United Kingdom—though a pilot study in this week's issue represents a first attempt to quantify the size of the problem (p 517).1 Alongside this is the difficulty of indicating risk. To a bereaved relative the knowledge that there was a 1 in 1000 risk is no consolation—for them it was 1 in 1. In a country where millions are spent every week on the national lottery the concept of risk is obviously alien. What is clear, however, is both that we need to know more about errors and to do more about them.

How common are errors? Can they be minimised? And how should we tackle risk management? One problem in assessing the frequency of errors is that we are deeply immersed in a blame culture, so it is hard to persuade people …
Life events and gastrointestinal symptom.
Authors: N J Talley, D W Piper
Journal: Gut (1986)

Mammalian Toll-like receptors (TLRs) are required for cell activation by bacterial lipoproteins (bLP) and LPS. Stimulation of monocytes with bLP and LPS results in a TLR-dependent induction of immunomodulatory genes leading to the production of pro-inflammatory cytokines. In this paper, we compared the expression and response of TLRs on monocytes and dendritic cells (DC). TLR2, but not TLR4, was detected on peripheral blood monocytes and DC, in lymphoid tissue CD1a<sup>+</sup> DC as well as on in vitro monocyte-derived DC. Upon stimulation with bLP or LPS, monocytes produced IL-12 and IL-10 at similar levels, whereas monocyte-derived DC produced comparable levels of IL-12, but little IL-10. Greater than 90% of the bLP-induced production of IL-12 was blocked by anti-TLR2 mAb. Thus, DC express TLR2 and activation of this receptor by bLP provides an innate mechanism by which microbial pathogens preferentially activate cell-mediated immunity.
ELECTROENCEPHALOGRAM AND MYOPATHY
Authors: Meyer A. Perlstein
Journal: JAMA (1960)

Electroencephalographic findings in 101 patients with muscular dystrophy and related myopathies are reported. Abnormal electroencephalograms were found in a total of 39 patients; 45 % of 62 patients with pseudohypertrophic muscular dystrophy, 18 % of 22 with amyotonia congenita, 37% of 8 with facioscapulohumeral dystrophy, and 45% of 9 with other myopathies and related syndromes. The most common abnormalities in the electroencephalogram were 14-and-6-per second positive spikes, seen especially in patients with pseudohypertrophic muscular dystrophy. Other abnormalities were spike seizure discharges, fast or slow frequency, asynchronous sleep patterns, and amplitude asymmetries. The electroencephalographic abnormalities increased with advancing age but were not related to severity of the seizures. It is suggested that the high incidence of abnormal electroencephalograms in patients with muscular dystrophy may be due to basic maturational neurophysiological involvement, an integral part of muscular dystrophy.
Prognosis, diagnosis, or who knows? Time to learn what gene tests mean
Authors: P. Cotton
Journal: JAMA (1995)

THE MUCH-HERALDED genetics revolution in medicine, though still largely limited to academe, is lurching relentlessly toward the primary care physician's door.  Tests for genes associated with common disorders like colon cancer and atherosclerosis are already on the market. Tests for genes linked to breast cancer, obesity, and a host of others are sure to follow.  A directory being compiled at Children's Hospital in Seattle, Wash, called Helix (soon to be on the Internet and available now by calling [206] 528-2689) shows that 192 laboratories are now testing for genes proved or suspected to be associated with 256 different diseases, says Roberta (Bonnie) Pagon, MD, a professor of pediatrics at the University of Washington School of Medicine.  Yet most observers say that few physicians, let alone lay citizens, are ready for all the ramifications of a science that has gone way beyond the simplicity of Gregor Mendel's sweet pea experiments.  There
Elevated Circulating Myeloid Derived Suppressor Cells (MDSC) Are Associated with Inferior Overall Survival (OS) and Correlate with Circulating Tumor Cells (CTC) in Patients with Metastatic Breast Cancer.
Authors: S. Cole, A. Montero, E. Garret-Mayer, G. Onicescu, T. Vandenberg, S. Hutchens, C. Diaz-Montero
Journal: Cancer Research (2009)

Abstract Background: MDSC acumulation is an important mechanism of tumor escape from immune surveillance and cancer progression. Pre-clinical studies have shown a correlation between tumor progression and MDSC. While we and others have shown that circulating MDSC correlate with clinical stage, to date there are few clinical studies that have explored the correlation of MDSC with metastatic tumor burden or as an adverse prognostic factor. Consequently, the goal of this study was to determine whether levels of MDSC in patients with stage IV breast cancer correlate with tumor burden using CTC and Swenerton Scores (SS) as surrogates for metastatic disease burden, and if circulating MDSC levels were predictive of overall survival.Methods: Flow cytometric analysis was performed on peripheral whole blood from 25 patients with stage IV breast cancer prior to initiation of therapy and at defined intervals during therapy. The MDSC population was defined as lineage-, CD33+, HLA-DR-, CD11b+. CTC (CellSearch®) and MDSC were drawn simultaneously and SS were calculated using a standardized scoring system previously defined and published in the literature. A generalized estimating equation regression model was created and fitted individually for each predictor. OS was defined as time of study enrollment to date of death.Results: Using a generalized estimating equation regression model the percentage of MDSC in peripheral blood was found to have a close correlation with CTC (Pearson correlation 0.62, p=0.0001) and a coefficient of 0.29 (0.14, 0.43 95%CI). The correlation between percent MDSC and SS was not significant (Pearson 0.31, p=0.12). Interestingly, no significant correlation between CTC and SS was noted either. MDSC levels were also found to predict OS in patients with the highest percentages at the first visit having significantly decreased median overall survival [6.8 vs. 19.6 months; p=0.05]Similarly, high MDSC levels at the final blood draw was also found to correlate with significantly shorter median OS [p=0.023].Conclusions. MDSC correlated well with CTC but not SS. High circulating MDSC levels were associated with significantly decreased overall survival in patients with metastatic breast cancer. MDSC appear to be a promising prognostic immunologic biomarker in metastatic breast cancer. Further studies are needed to better define the role of MDSCs in breast cancer progression and may be a useful therapeutic target to enhance the effectiveness of immune based therapies in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4135.
Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia.
Authors: P H McNulty, A J Sinusas, C Q Shi, D Dione, L H Young, G C Cline, G I Shulman
Journal: Journal of Clinical Investigation (1996)

Myocardial regions perfused through a coronary stenosis may cease contracting, but remain viable. Clinical observations suggest that increased glucose utilization may be an adaptive mechanism in such "hibernating" regions. In this study, we used a combination of 13C-NMR spectroscopy, GC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-13C]glucose during a 3-4-h period of acute ischemic hibernation. During low-flow ischemia [3-13C]alanine enrichment was higher, relative to plasma [1-13C]glucose enrichment, in ischemic than in nonischemic regions of the heart, suggesting a greater contribution of exogenous glucose to glycolytic flux in the ischemic region (approximately 72 vs. approximately 28%, P < 0.01). Both the fraction of glycogen synthase present in the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rate of incorporation of circulating glucose into glycogen (94 +/- 25 vs. 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady state [4-13C)glutamate/[3-13C]alanine enrichment ratios demonstrated that glucose-derived pyruvate supported 26-36% of total tricarboxylic acid cycle flux in all regions, however, indicating no preference for glucose over fat as an oxidative substrate in the ischemic myocardium. Thus during sustained regional low-flow ischemia in vivo, the ischemic myocardium increases its utilization of exogenous glucose as a substrate. Upregulation is restricted to cytosolic utilization pathways, however (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.
Pseudocoarctation, Kinking or Buckling of the Aorta
Authors: PETER T. SMYTH, JESSE E. EDWARDS
Journal: Circulation (1972)

Pseudocoarctation, buckling, and kinking of the aorta are terms used to describe a roentgenologic deformity of the aorta similar to that in classical coarctation but in which no obstruction is demonstrable. It is probable that the first three terms used are synonyms for subclinical coarctation. In this state, the lesion of classical coarctation of the aorta is present and the two show the same associated anomalies.
Clearing of Pyoderma gangrenosum by intralesional cyclosporin A
Authors: U. Mrowieiz, E. Christophers
Journal: British Journal of Dermatology (1991)

Journal Article Clearing of Pyoderma gangrenosum by intralesional cyclosporin A Get access U. Mrowieiz, U. Mrowieiz Department of Dermatology, University of Kiel, Schittenhebnstrasse 7, D‐2300 Kiel, Germany Search for other works by this author on: Oxford Academic Google Scholar E. Christophers E. Christophers Department of Dermatology, University of Kiel, Schittenhebnstrasse 7, D‐2300 Kiel, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 5, 1 November 1991, Page 499, https://doi.org/10.1111/j.1365-2133.1991.tb14783.x Published: 01 November 1991
Vineyard snail allergy possibly induced by sensitization to house‐dust mite (<i>Dermatophagoides pteronyssinus</i>)
Authors: F. De Maat‐Bleeker, J. H. Akkerdaas, R. van Ree, R. C. Aalberse
Journal: Allergy (1995)

A female patient experienced a severe allergic reaction after consumption of vineyard snails. The patient proved to be sensitized to house‐dust mite (HDM) and demonstrated a positive skin test and specific IgE to snail ( Eobania vermiculata , Lofarma). The snail RAST was &gt; 80% inhibited by HDM, whereas the mite RAST was &lt; 10% inhibited by snail extract. This is possibly another example of food allergy related to primary sensitization by an aeroallergen.
Ineffective surgical procedures are used to treat Canadians with osteoarthritis
Authors: B. Kermode-Scott
Journal: BMJ (2010)

Thousands of unnecessary therapeutic knee arthroscopies and vertebroplasties continue to be carried out in Canada despite evidence that the procedures are essentially ineffective, reports the Canadian Institute for Health Information.

In December, the institute reported in Health Care in Canada 2010 , that in 2008-9 more than 3600 therapeutic knee arthroscopies were performed in Canadian hospitals, despite mounting evidence from randomised controlled trials that the procedure is of little benefit.

The authors explained that studies suggest that arthroscopies fail to improve patient outcomes or reduce discomfort when used to treat osteoarthritis. Also, a substantial number of patients go on to …