tbuckley/cabot-search huggingface dataset:
Environment of infants during sleep and risk of the sudden infant death syndrome: results of 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy
Authors: P. J Fleming, P. S Blair, C. Bacon, D. Bensley, I. Smith, E. Taylor, J. Berry, J. Golding, J. Tripp
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To investigate the role of sleeping arrangements as risk factors for the sudden infant death syndrome after a national risk reduction campaign. <b>Design</b>: Two year population based case-control study. Parental interviews were conducted for each infant who died and for four controls matched for age and date of interview. <b>Setting</b>: Three regions in England with a total population of 17 million people. <b>Subjects</b>: 195 babies who died and 780 matched controls. <b>Results</b>: Prone and side sleeping positions both carried increased risks of death compared with supine when adjusted for maternal age, parity, gestation, birth weight, exposure to smoke, and other relevant factors in the sleeping environment (multivariate odds ratio = 9.00 (95% confidence interval 2.84 to 28.47) and 1.84 (1.02 to 3.31), respectively). The higher incidence of side rather than prone sleeping led to a higher population attributable risk (side 18.4%, prone 14.2%). More of the infants who died were found with bed covers over their heads (21.58; 6.21 to 74.99). The use of a dummy had an apparent protective effect (0.38; 0.21 to 0.70). Bed sharing for the whole night was a significant risk factor for infants whose mothers smoked (9.25; 2.31 to 34.02). No protective effect of breast feeding could be identified on multivariate analysis. <b>Conclusions</b>: This study confirms the importance of certain risk factors for the sudden infant death syndrome and identifies others—for example, covers over the head, side sleeping position—which may be amenable to change by educating and informing parents and health care professionals. <h3>Key messages</h3> This large case-control study is the first after the national campaign to reduce the risk of the syndrome The risk of sudden infant death is increased by prone or side sleeping position; loose bedding (particularly duvets), which can slip over the baby9s head; and bed sharing by mothers who smoke The risk may be reduced by supine sleeping position; placing the baby with feet at the foot of the cot (“feet to foot”); ensuring that bedding is securely tucked in; and avoiding the use of duvets
Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders
Authors: F K Goodwin, A J Prange, R M Post, G Muscettola, M A Lipton
Journal: American Journal of Psychiatry (1982)

Six women and 6 men who were treated in double-blind fashion major depressive illness did not respond to imipramine or amitriptyline, 150-300 mg/day, during periods of 26-112 days. After the addition of 25 micrograms/day (10 patients) or 50 micrograms/day (2 patients) of L-triiodothyronine (T3), 9 patients showed statistically significant improvement in depression scores; in 8 patients the response was marked. Improvement generally began within 1-3 days and was noted in all aspects of the depressive syndrome; side effects were minimal. T3 did not change plasma levels of imipramine or desipramine or their ratio but did suppress serum thyroxine.
Eating and Its Disorders.
Authors: Albert J. Stunkard, Eliot Stellar
Journal: Annals of Internal Medicine (1984)

This latest contribution (Volume 62) in the series of research monographs of the Association for Research in Nervous and Mental Disease covers mechanisms and disorders of eating. The 19 chapters are organized in three major sections: The first deals with basic neuroanatomic and chemical concepts, the second describes current physiologic concepts that underlie the regulation of body weight, and the final section reviews treatment of obesity, anorexia nervosa, and bulimia. Beginning with Stellar's  of hypothalamic control, proposed 30 years ago, the complexities of neuroanatomic mechanisms that underlie hunger and satiety, the role of neurotransmitters, and the interaction of peripheral with central mechanisms that regulate eating are updated in light of research advances. The recent hypothesis of the relationship of postprandial satiety to cholecystokinin and also the regulating effects of dietary amino acids are reviewed by Smith and the Wurtmans. A section on the regulation of body weight deals particularly with the set-point theory of body weight maintenance. The roles of adipose tissue, lean body mass, and physical activity in the metabolic defense of weight are thoroughly reviewed. Herman and Polivy suggest a novel boundary model for the regulation of eating, which begins to consider the interactional complexities of biologic and psychosocial forces in different persons. The final section considers the treatment of obesity in adults, in children, and in adolescents, the treatment of anorexia nervosa, and the treatment of bulimia. Stunkard provides a reasoned account of the current status of treatment of excessive weight which is based on classifying obesity by its severity. The Wooleys provocatively challenge whether obesity should be treated at all, but their thesis has a polemic ring. Agras and Kraemer provide the beginnings of a much needed evaluation of the treatment of anorexia nervosa but maintain a surprisingly limited view of what constitutes recovery. An essay on the psychopathologic features of anorexia nervosa by Crisp furnishes a much broader perspective on treatment complexities. Two diverse approaches to the treatment of bulimia—cognitive behavior therapy and antidepressant medication—reflect the current limited understanding of this condition.
Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in β-islet cell hyperplasia
Authors: Sushil G. Rane, Pierre Dubus, Richard V. Mettus, Elizabeth J. Galbreath, Guenther Boden, E. Premkumar Reddy, Mariano Barbacid
Journal: Nature Genetics (1999)
261. Immune Evasion in Gene Therapy
Authors: Rob C. Hoeben, Martine Ossevoort, Birgit M. Visser, Arnaud Zaldumbide, Ellen I. Van der Voort, Diana J. Van den Wollenberg, Rene E. Toes
Journal: Molecular Therapy (2004)

A problem associated with the gene-therapy concept is the T cell-mediated immune response, which is elicited by synthesis and presentation of transgene-derived and vector-derived peptides and which leads to rapid clearance of the transduced cells and loss of transgene expression. One way to avoid the immune response is by blocking the ubiquitin/proteasome pathway. Interference in this pathway is widely applied by viruses, for instance by Epstein-Barr virus (EBV) in its nuclear antigen 1 (EBNA-1). EBNA-1 is required for the maintenance of the viral episomes in the infected cells. Although EBNA-1 specific CTL have been described, they cannot recognize EBV-infected cells. The failure to recognize endogenously expressed EBNA-1 has previously been attributed to a glycine-alanine rich (GAr) stretch in the EBNA-1 sequence that protects the protein from proteasomal degradation. We have shown previously that inclusion of the full length EBNA-1 derived GAr domain could be exploited to abrogate CTL-induced killing of cells expressing the transgene (ref 1). Firstly we demonstrated that inclusion of the EBNA-1 derived GAr domain does not interfere with enzyme function. We tested three different enzymes that all retained their activity. In addition, a recombinant adenovirus expressing GAr-containing β-galactosidase was able to deliver functional enzyme in vivo. However, expression of the GAr-β-gal as well as the control β-gal resulted in the induction of a strong β-galactosidase-specific CTL response. This can be attributed to cross-priming, as vaccination of BALB/c mice (H-2d) with C57Bl/6 (H-2b) fibroblasts expressing GAr-β-galactosidase resulted in the induction of β-gal-specific CTLs. Nonetheless, LacZ-specific CTL did not recognize target cells expressing GAr-LacZ in vitro. These results showed that the GAr can be exploited to create 'stealth' genes by hiding specific foreign antigens from CTL-mediated immune-attack. Currently, we are testing the hypothesis that fusion with the GAr will lead to a prolonged expression of transgenes in vivo. Preliminary evidence indicates that the modification leads to prolonged expression of β-gal in vivo after adenovirus-mediated intra-muscular gene transfer. In addition, we generated stable B16 mouse melanoma cell lines expressing either thymidine kinase (TK) or GAr-TK. The tumor take and survival of these cells in C57Bl/6 mice are being studied either in the presence or in the absence of antigen-specific CTL.
Thyroid hormone and hair growth
Authors: A.G. Messenger
Journal: British Journal of Dermatology (2000)

Diffuse loss of scalp, body and eyebrow hair are well‐recognized clinical signs of thyroid deficiency, known to generations of medical students. Thyroid hormone also affects hair growth in other species. In rats thyroxine increases and thiouracil decreases the final length of hair (reviewed 1). Thyroxine increases the rate of hair growth in sheep 2 and, in badgers, hair growth and seasonal moulting ceased following thyroidectomy and resumed when the animals were treated with thyroxine. 3 Objective studies of the effect of thyroid hormone on human hair growth are, however, thin on the ground. Freinkel and Freinkel found high telogen counts in scalp hair in nine hypothyroid subjects, which were corrected following thyroid replacement therapy. 4 Jackson and colleagues compared scalp hair diameters in groups of hypothyroid women, women with female pattern balding and normal women. 5 In women with normal hair density, hair diameters showed a symmetrical distribution with a single peak at 80 µm. Mean hair diameter was reduced in the hypothyroid and euthyroid balding women and in both groups hair diameters showed a similar bimodal distribution. They suggested that hair loss in hypothyroidism only occurs when the condition adds to or accelerates a familial tendency. The effect of thyroid status on human hair growth has also been demonstrated at the cellular level. Using DNA flow cytometry, Schell et al. observed that cell proliferation indices were reduced in hair bulbs of hypothyroid subjects and increased in hyperthyroidism compared with normal values. 6
Re: Johan Lindberg, Anna Kristiansen, Peter Wiklund, Henrik Grönberg, Lars Egevad. Tracking the Origin of Metastatic Prostate Cancer. Eur Urol 2015;67:819–22
Authors: Francesco Piva, Matteo Santoni, Marina Scarpelli, Alberto Briganti, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2015)
Prognostic Significance of ST Segment Shift Early After Resolution of ST Elevation in Patients With Myocardial Infarction Treated With Thrombolytic Therapy: The GUSTO-I ST Segment Monitoring Substudy 11This study was supported by Genentech Canada Inc., Toronto, Ontario, Canada; Kabi Vitrum, Sweden; Bayer, New York, New York; Sanofi Pharmaceuticals, Paris, France; ICI Pharmaceuticals, Wilmington, Delaware; Marquette Electronics, Milwaukee, Wisconsin; Ortivus Medical, Stockholm, Sweden; and …
Authors: Anatoly Langer, Mitchell W. Krucoff, Peter Klootwijk, Maarten L. Simoons, Christopher B. Granger, Aiala Barr, Robert M. Califf, Paul W. Armstrong
Journal: Journal of the American College of Cardiology (1998)
Abstract 2865: High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma
Authors: Tzu-Hsuan Lin, Yu-Yun Shao, Soa-Yu Chan, Chung-Yi Huang, Ann-Lii Cheng, Chih-Hung Hsu
Journal: Cancer Research (2014)

Abstract Background: TGF-β (Transforming growth factor β) signaling pathway plays a significant role in mediating progression, metastasis, and immune evasion of human malignancies. Previous studies have found that serum TGF-β1 levels were elevated in patients with hepatocellular carcinoma (HCC) compared to patients with chronic hepatitis or cirrhosis. However, the prognostic role of serum TGF-β1 levels in patients with advanced HCC is currently unknown. Patients and Methods: We enrolled patients who had received sorafenib or sorafenib-based combination therapy for advanced HCC, defined as metastatic or locally advanced diseases not amenable to loco-regional therapies, at National Taiwan University Hospital, Taipei, Taiwan, between 2007 and 2012. The baseline blood samples were collected before sorafenib treatment with the consent of the patients. Serum TGF-β1 levels were measured by Human TGF-β1 Instant ELISA (eBioscience, Vienna, Austria), and were correlated with disease control rate (DCR), progression- free survival (PFS), and overall survival (OS) of the patients. Results: The study enrolled 91 patients (M:F=82:9), with a median age of 56.9 years. Sixty-nine patients (75.8 %) had chronic hepatitis B virus (HBV) infection, 18 (19.7%) had chronic hepatitis C infection, 82 (90.1%) had Barcelona Clinic Liver Cancer stage C disease, 81(89.0%) had either extrahepatic metastasis or macrovascular invasion, and 88 (96.7%) had Eastern Cooperative Oncology Group performance status of ≤ 1. All patients had Child-Puch class A liver function reserve. Patients with high baseline serum TGF-β1 levels (higher than the median level of the whole patient cohort), compared to patients with low serum TGF-β1 levels, had significantly shorter PFS (median, 2.54 vs. 4.27 months, p = 0.022) and OS (median, 5.57 vs. 11.6 months, p = 0.029). The DCRs for patients with high and low TGF-β1 were not statistically different (54.3 % vs. 62.2%, p = 0.4463). High baseline TGF-β1 levels tended to associate with high serum alpha-fetal protein (AFP) levels and high Cancer of the Liver Italian Program (CLIP) scores, although not reaching statistical significance. Conclusions: High baseline serum TGF-β1 levels were associated with poor PFS and OS in patients with advanced HCC. (This study was supported by grants NRPB-100CAP1020-2, NSC101-2314-B-002-141 &amp; NSC102-2314-B-002 -120). Citation Format: Tzu-Hsuan Lin, Yu-Yun Shao, Soa-Yu Chan, Chung-Yi Huang, Ann-Lii Cheng, Chih-Hung Hsu. High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma. [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 2865. doi:10.1158/1538-7445.AM2014-2865
Abstract P236: Improving Cardiovascular Risk Prediction in Type II Diabetes Patients with Repeated Measurements of Clinical Biomarkers
Authors: Linda M Peelen, Lily Nagtzaam, Joline W Beulens, Susan Van Dieren, Karel G Moons, Yvonne T Van der Schouw
Journal: Circulation (2015)

Background:  Patients with type 2 diabetes (DM2) are at increased risk of cardiovascular disease (CVD) and treated for risk factors such as hypercholesterolemia and hypertension. HbA1c, cholesterol, blood pressure are monitored at regular time intervals, eg quarterly or annually. It is unknown whether these repeated measurements improve CVD risk prediction in DM2 patients.   Methods:  We simulated a cohort of 2,000 patients based on existing data, in which we modelled treatment of diabetes and risk factors according to Dutch guidelines. All subjects were treated with a sulfonylurea-derivative, and subjects with increased baseline CVD risk were treated with simvastatin and/or antihypertensive medication. Reductions in HbA1c, blood lipids, blood pressure and CVD risk were modelled according to literature (timepoint 1). If target values were not reached, patients were treated with insulin, atorvastatin, and a second antihypertensive agent (timepoint 2). In the simulated dataset CVD risk prediction at baseline was compared with 3 approaches to include repeated measurements: 1) use latest values of clinical biomarkers in existing risk score;2) remodel risk score using latest values;3) remodel risk score using baseline plus latest values. The approaches were compared by discrimination and calibration.   Results:  Table 1 shows the performance of the approaches at both time points. Calibration was acceptable in all settings except approach 1 at time 2 (p = 0.03). C statistics showed small differences between approaches; it slightly diminished with approach 1, and improved when fitting a new model with both the repeated and baseline value. Other treatment scenarios yielded comparable results.   Conclusion:  Differences in C statistics between the approaches are comparable in order of magnitude with differences between entire risk scores or added value of biomarkers in this clinical domain. Thus, although concrete recommendations cannot be made yet, including repeated measures in CVD prediction for DM2 patients may be promising.
Histone Deacetylase Inhibition Rescues Maternal Deprivation-Induced GABAergic Metaplasticity through Restoration of AKAP Signaling
Authors: Michael E. Authement, Jayaraj N. Kodangattil, Shawn Gouty, Milan Rusnak, Aviva J. Symes, Brian M. Cox, Fereshteh S. Nugent
Journal: Neuron (2015)
Achalasia
Authors: John E. Pandolfino, Andrew J. Gawron
Journal: JAMA (2015)

<h3>Importance</h3> Achalasia significantly affects patients' quality of life and can be difficult to diagnose and treat. <h3>Objective</h3> To review the diagnosis and management of achalasia, with a focus on phenotypic classification pertinent to therapeutic outcomes. <h3>Evidence Review</h3> Literature review and MEDLINE search of articles from January 2004 to February 2015. A total of 93 articles were included in the final literature review addressing facets of achalasia epidemiology, pathophysiology, diagnosis, treatment, and outcomes. Nine randomized controlled trials focusing on endoscopic or surgical therapy for achalasia were included (734 total patients). <h3>Findings</h3> A diagnosis of achalasia should be considered when patients present with dysphagia, chest pain, and refractory reflux symptoms after an endoscopy does not reveal a mechanical obstruction or an inflammatory cause of esophageal symptoms. Manometry should be performed if achalasia is suspected. Randomized controlled trials support treatments focused on disrupting the lower esophageal sphincter with pneumatic dilation (70%-90% effective) or laparoscopic myotomy (88%-95% effective). Patients with achalasia have a variable prognosis after endoscopic or surgical myotomy based on subtypes, with type II (absent peristalsis with abnormal pan-esophageal high-pressure patterns) having a very favorable outcome (96%) and type I (absent peristalsis without abnormal pressure) having an intermediate prognosis (81%) that is inversely associated with the degree of esophageal dilatation. In contrast, type III (absent peristalsis with distal esophageal spastic contractions) is a spastic variant with less favorable outcomes (66%) after treatment of the lower esophageal sphincter. <h3>Conclusions and Relevance</h3> Achalasia should be considered when dysphagia is present and not explained by an obstruction or inflammatory process. Responses to treatment vary based on which achalasia subtype is present.
Euthanasia in Belgium and the Netherlands
Authors: Barron H. Lerner, Arthur L. Caplan
Journal: JAMA Internal Medicine (2015)

20. Kuiken A. Was haar leven nog leefbaar? Trouw. January 11, 2014. http://www.trouw.nl/tr/nl/4516 /Gezondheid/article/detail/3575826/2014/01/11 /Was-haar-leven-nog-leefbaar.dhtml. Accessed July 6, 2015. 21. Bolt EE, SnijdewindMC,Willems DL, van der Heide A, Onwuteaka-Philipsen BD. Can physicians conceive of performing euthanasia in case of psychiatric disease, dementia or being tired of living [published online February 18, 2015]? J Med Ethics. doi:10.1136/medethics-2014-102150. 22. van Tol D, Rietjens J, van der Heide A. Judgment of unbearable suffering and willingness to grant a euthanasia request by Dutch general practitioners.Health Policy. 2010;97(2-3):166-172. 23. Muller MT, Onwuteaka-Philipsen BD, van derWal G, van Eijk J, RibbeMW. The role of the social network in active euthanasia and physician-assisted suicide. Public Health. 1996;110 (5):271-275.
Primary cutaneous B-cell lymphoma: how useful is the new European Organization for Research and Treatment of Cancer (EORTC) classification?
Authors: None Russell-Jones
Journal: British Journal of Dermatology (1998)

The classification of non‐Hodgkin's lymphoma has undergone extensive revision in recent years, particularly with the development of immunophenotypic and genotypic criteria. While most general pathologists now rely upon the Revised European and American Classification of Lymphoma neoplasms (REAL), the cutaneous lymphoma project group of the European Organization for Research and Treatment of Cancer (EORTC) has put forward its own proposal for the classification of primary cutaneous lymphomas. While this is understandable in the context of cutaneous T‐cell lymphoma, the EORTC classification of primary cutaneous B‐cell lymphoma has proved more controversial: first, because chromosomal changes are largely excluded; secondly, because follicle centre cell lymphoma in the skin is imprecisely defined; and thirdly, because large B‐cell lymphoma of the leg is included as a separate entity. This review identifies the main differences between the two systems of classifying B‐cell lymphomas in the skin, and the areas of research required to clarify some of the outstanding issues. Pathologists are unlikely to adopt the EORTC proposals for B‐cell neoplasms until these issues have been resolved.
Abstract 15776: Determination of Maximum Isotherm to Achieve Conduction Block During Cryoablation
Authors: Karoly Kaszala, Jose F Huizar, Alex Tan, Kenneth A Ellenbogen
Journal: Circulation (2014)

Introduction: Thermal characteristics of cryoablation to achieve myocardial conduction block is not well understood. In this study we evaluated the maximum isotherm during cryoablation to achieve conduction block. Methods: Anesthetized, ventilated canines (n=9) underwent thoracotomy. In in-situ RV outflow tract, blind alley (BA) that conducted to and from the RV only via an isthmus (IS) was created by cut and sew method by making a surgical incision. Cryoablation (7Fr, 8 mm tip FreezorMax3, Medtronic) was performed (4 -6 min per lesion) from the endocardium at the IS. Epicardial temperature was monitored by a thermal camera (FLIR, Danderyd, Sweden). Conduction block was assessed by pacing and recording from inside the BA and from the LV. Acute and chronic block was defined as bidirectional block through the IS at 15 min and 180 min, respectively. Ablation was continued until acute block was achieved and observation continued for 180 min. Results: Ten preparations were studied. Acute block was achieved in all preparations. IS temperature was ≤ -10C in all samples with chronic block (4/8, p=0.028) and &gt;-10C without chronic block (4/8). Chronic block was not assessed in two due to delay in achieving acute block. Ablation data is summarized in the Table. Conclusion: We presented a novel in-vivo large animal model that allows in-situ assessment of temperature changes and conduction. Tissue cooling below -10C is required during cryoablation to achieve prolonged (180 min) conduction block.
Curate given go-ahead to challenge decision over abortion
Authors: R. Dobson
Journal: BMJ (2003)

The High Court has given the go-ahead for a legal challenge to a decision by the police not to prosecute doctors involved in a late abortion carried out on a woman whose fetus had a cleft palate.

Reverend Joanna Jepson was given permission to launch a judicial review of the decision by West Mercia Police in a legal action that could lead to a tightening up of the abortion law and to a clearer definition of what constitutes a serious handicap.

The 27 year old curate's original application for a judicial …