tbuckley/cabot-search huggingface dataset:
Clinical and Genetic Problems in Familial Intestinal Polyposis
Authors: A. M. O. Veale
Journal: Gut (1960)

The history of a family suffering from familial intestinal polyposis is presented, showing how a delayed onset of symptoms together with a lack of knowledge of affected relatives may obscure the familial nature of the disease. The necessity of examining all accessible relatives, irrespective of their advancing years, is stressed. Further, it is shown that in the absence of any familial incidence the proper diagnosis of an isolated case of polyposis is that the disease is the result of a fresh mutation. The possibility of a non-familial form of this disease cannot be proved at present and will require a special genetic investigation. It is emphasized that the diagnosis of non-familial polyposis should not be made, as this will lead to a relaxation of the vigil that should be kept on the descendants of all patients with polyposis.
An Adult with Type 2 Citrullinemia Presenting in Europe
Authors: Giuseppe Fiermonte, Derek Soon, Abhijit Chaudhuri, Eleonora Paradies, Philip J. Lee, Steve Krywawych, Ferdinando Palmieri, Robin H. Lachmann
Journal: New England Journal of Medicine (2008)

To the Editor: Type 2 citrullinemia is an adult-onset, autosomal recessive disorder characterized by episodes of hyperammonemic encephalopathy. It is caused by mutations in the SLC25A13 gene, which...
Internalized constraints in the representation of spatial layout
Authors: Helene Intraub
Journal: Behavioral and Brain Sciences (2001)

Shepard's (1994) choice of kinematic geometry to support his theory is questioned by Todorovic, Schwartz, and Hecht. His theoretical framework, however, can be applied to another domain that may be less susceptible to some of their concerns. The domain is the representation of spatial layout. [Hecht; Schwartz; Shepard; Todorovič]
15-Hydroxyprostaglandin Dehydrogenase Is a Tumor Suppressor of Human Breast Cancer
Authors: Ido Wolf, James O'Kelly, Tamar Rubinek, Min Tong, Anh Nguyen, Bryan T. Lin, Hsin-Hsiung Tai, Beth Y. Karlan, H. Phillip Koeffler
Journal: Cancer Research (2006)

Abstract Prostaglandin E2 plays a growth-stimulatory role in breast cancer, and the rate-limiting enzyme in its synthesis, cyclooxygenase-2, is often overexpressed in these cancers. Little is known about the role of the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in breast cancer pathogenesis. Using a pharmacologically based screen for epigenetically silenced genes, we found low levels of 15-PGDH in MDA-MB-231 cells [estrogen receptor (ER) negative] but high levels in MCF-7 cells (ER positive) and observed its up-regulation following demethylation treatment. Further analysis revealed methylation of the 15-PGDH promoter in one breast cancer cell line and 30% of primary tumors. Analysis of 15-PGDH expression revealed low levels in 40% of primary breast tumors and identified a correlation between 15-PGDH and ER expression. Transfection assays showed that transient up-regulation of 15-PGDH levels in MDA-MB-231 cells resulted in a decreased clonal growth, and stable up-regulation significantly decreased the ability of these cells to form tumors in athymic mice. In contrast, transient silencing of 15-PGDH in MCF-7 cells resulted in their enhanced proliferation, and a stable silencing in these cells enhanced cell cycle entry in vitro and tumorigenicity in vivo. Forced expression of 15-PGDH inhibited the ER pathway and silencing of 15-PGDH up-regulated expression of aromatase. In addition, 15-PGDH levels were down-regulated by estrogen but up-regulated by the tumor suppressor gene CAAT/enhancer binding protein α. Our results indicate for the first time that 15-PGDH may be a novel tumor suppressor gene in breast cancer, and suggest that this enzyme can modulate the ER pathway. (Cancer Res 2006; 66(15): 7818-23)
Chronic hepatitis B and hepatocarcinogenesis: Does prevention of “collateral damage” bring the cure?
Authors: Tobias Manigold, Barbara Rehermann
Journal: Hepatology (2003)

A persistent immune response to hepatitis viruses is a well-recognized risk factor for hepatocellular carcinoma.However, the molecular and cellular basis for the procarcinogenic potential of the immune response is not well defined.Here, using a unique animal model of chronic hepatitis that induces hepatocellular carcinogenesis, we demonstrate that neutralization of the activity of Fas ligand prevented hepatocyte apoptosis, proliferation, liver inflammation, and the eventual development of hepatocellular carcinoma.The results indicate that Fas ligand is involved not only in direct hepatocyte killing but also in the process of inflammation and hepatocellular carcinogenesis in chronic hepatitis.This is the first demonstration that amelioration of chronic inflammation by some treatment actually caused reduction of cancer development.(2) Sitia G, Isogawa M, Kakimi K, Wieland SF, Chisari FV, Guidotti LG.Depletion of neutrophils blocks the recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of hepatitis B virusspecific cytotoxic T lymphocytes.
Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor.
Authors: H Kodama, A Yamasaki, M Nose, S Niida, Y Ohgame, M Abe, M Kumegawa, T Suda
Journal: The Journal of Experimental Medicine (1991)

Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and peritoneal macrophages because of a defect in the production of functional macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the M-CSF gene. In this study, we examined whether daily 5-microgram injections of purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies in the mutant mice. Monocytes in the peripheral blood of the op/op mice were significantly increased in number after subcutaneous injections of the factor two or three times a day. In contrast, osteopetrosis in the long bones of op/op mice was completely cured by only one injection of rhM-CSF per day. Bone trabeculae in the diaphyses were removed. Many osteoclasts were detected on the surface of bone trabeculae in the metaphyses. Although development of tooth germs of uninjected op/op mice was impaired, rhM-CSF injection restored the development of molar tooth germs and led to tooth eruption as a consequence of the recovery of bone-resorbing activity. These results demonstrate that M-CSF is one of the factors responsible for the differentiation of osteoclasts and monocyte/macrophages under physiological conditions.
Therapy Motivation in Anorexia nervosa: Theory and First Empirical Results
Authors: K. Engel, H. Wilms
Journal: Psychotherapy and Psychosomatics (1986)

Anorexia nervosa patients are considered to be unmotivated for psychotherapy of eating disorders, because they present a lack of understanding and feeling for their disease. In order to objectify this lack of therapy motivation we formulated two questionnaires for patients and therapists. The items were obtained from 15 theoretically determined fields of both intra- and inteφersonal subsets of motivation, and a 'motivation profile' was gained. In a first clinical application these profiles are obtained from an anorexia sample at the beginning and at the end of an inpatient treatment and combined with the corresponding therapist ratings. The results are compared with two control groups (preattended psychosomatics and somatic patients). Results collected hereby are used for the improvement of our questionnaires and for suggestions concerning further studies.
Access to civil justice: Lord Woolf's visionary new landscape
Authors: S. Burn
Journal: BMJ (1996)

a homogeneous patient group with major depression defined by the criteria of the Diagnostic and Statistical Manual ofMental Disorders.7 Like synthetic antidepressants, hypericum extract needs two to four weeks to develop its mood elevating effects.The herb may offer an advantage, however, in terms of relative safety and tolerability, which might improve patient compliance.So far, its extensive use in Germany has not resulted in published case reports about serious drug interactions or toxicity after overdose.In an open study of 3250 patients the most commonly noted side effects were gastrointestinal symptoms (0.6%), allergic reactions (0.5%), and fatigue (0.4%).Whether the allergic reactions could have been related to the photosensitising potential of hypericin was not investigated.The study lasted only four weeks, and laboratory values were not systematically monitored. 4 All in all, it is for good reasons that Linde et al ask for addi- tional studies with better delineation of participants and for 1 Lohse MJ, Misller-Oerlinghausen B. Psychopharmaka.
Sensitivity to Taxane Chemotherapy for Metastatic Breast Cancer in BRCA1 and BRCA2 Mutation Carriers Compared to Sporadic Breast Cancer Patients.
Authors: C. Seynaeve, A. Jager, M. Hooning, M. den Bakker, M. Bontenbal, J. Blom, M. Collee, A. van den Ouweland, M. Kriege
Journal: Cancer Research (2009)

Abstract Purpose: Data of in vitro and small retrospective studies suggest that breast cancer (BC) (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to chemotherapeutic agents causing double strand DNA breaks, while sensitivity to spindle poisons, such as paclitaxel and docetaxel, has been found to be decreased. Clinical data on the latter, however, are very scarce. In this study, we assessed the sensitivity to taxane chemotherapy for metastatic BRCA1/2-associated compared with sporadic breast cancer.Methods: From the family cancer clinic database, we retrieved 36 BRCA1 and 13 BRCA2-associated BC patients treated with taxane chemotherapy for metastatic disease before October 1, 2008, and with available data on follow-up and response assessment. Objective response (OR), and progression-free survival (PFS) after start of taxane chemotherapy were compared with those of 62 sporadic patients with comparable age at diagnosis and year of detection of metastatic BC. A t-test or chi-square test was used to test for differences in characteristics and response types, and Kaplan-Meier survival analysis to calculate PFS.Results: Taxane chemotherapy consisted of docetaxel (n= 76) or paclitaxel (n=21), while 10 (9%) patients received a taxane/trastuzumab regimen. It was given as first-line palliative therapy in 9 BRCA1, 1 BRCA2 and 22 sporadic patients; but mainly as second/third line treatment (BRCA1 n=27, BRCA2 n=12, sporadic patients n=40, respectively). As compared to sporadic patients, BRCA1-associated patients had a significantly lower OR rate (ORR) overall (22% vs 46%, p&amp;lt;0.001) and to 2nd/3rd line taxane treatment (19% vs 46%, p&amp;lt;0.001). Median PFS was shorter in BRCA1 patients (2.0 vs 4.1 mo, p=0.08), with a trend for significance for 2nd/3rd line therapy (1.6 vs 3.9 mo, p=0.05). Also, compared to BRCA2 patients, the ORR in BRCA1 patients was significantly lower, overall as well as to 2nd/3d line therapy (both p=0.003). In BRCA2 mutation carriers compared to sporadic patients, the ORR was higher (75% vs 48%, p=0.28) and PFS longer (6.4 vs 4.1 mo, p=0.33). After exclusion of the patients receiving a taxane/trastuzumab schedule, similar data were observed.Conclusion: Objective response rate to taxane chemotherapy for metastatic disease is lower in BRCA1-associated BC in comparison with sporadic as well as BRCA2-associated BC, resulting in a shorter PFS. If confirmed, these data may have substantial clinical relevance. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2098.
US supplied phosphorus shells used in Gaza, says Amnesty International
Authors: C. Dyer
Journal: BMJ (2009)

<h3>Background:</h3> People experiencing homelessness have significantly shorter life expectancies and higher rates of morbidity and mortality than the general population. Many barriers have been identified to providing palliative care to this population. This study examines health and social service providers9 experiences providing end-of-life care to people experiencing homelessness, seeking recommendations to improve both patient and provider experience. <h3>Methods:</h3> Qualitative study using phenomenological approach. Qualitative and quantitative surveys with 136 health and social service providers in Ontario9s South East Local Health Integration Network, in-depth interview with 10 key informants. <h3>Findings:</h3> Participants approached the end-of-life care of people experiencing homelessness from a framework of dignity and respect. Themes included barriers to end-of-life care internal to the health care system; care avoidance; the experience of stigma for this population when accessing end-of-life care; lack of provider information and awareness on how to provide care for marginalized groups, how to provide care in the context of substance use, and how to assist clients in accessing the formal palliative care system; and the need for harm reduction approaches to end-of-life care for persons experiencing homelessness. <h3>Discussion:</h3> Focusing on harm reduction, and using the framework of Equity-Oriented Health Care to make systemic, cultural, and policy changes to develop a palliative-care system for persons experiencing homelessness may improve care experience for both patients and providers.
831-1 Ruptured diabetic atherosclerotic plaques have more inflammation and neovascularization than ruptured plaques from patients without diabetes
Authors: K Raman Purushothaman, William N O'Connor, Dario Echeverri, Chikezie Amadi, Juan J Badimon, Valentin Fuster, Pedro R Moreno
Journal: Journal of the American College of Cardiology (2004)
Sympathetic Denervation and the Bone Scan
Authors: BRIAN C. LENTLE, GEORGE A. GLAZEBROOK, JOHN S. PERCY, FRANK I. JACKSON
Journal: Clinical Nuclear Medicine (1977)

Three patients, all having sustained a unilateral lower limb sympathectomy, are described. In all three uptake of bone-seeking tracer in the affected limb was increased with this increase being accentuated at the metaphyses of the long bones.
Human immunodeficiency virus infection and high c-reactive protein correlates with increased in-stent restenosis rate
Authors: Spyros Kokolis, George Dangas, Roxana Mehran, Ronald Kokolis, Zoran Lasic, Ruby Hanna, Michael Collins, Sriram Iyer, Makoto Hirose, Yoshio Kobayashi, Edward Kreps, Gregg W. Stone, Martin B. Leon, Jeffrey W. Moses
Journal: Journal of the American College of Cardiology (2003)
Who is mind blind?
Authors: Nicholas Nicastro
Journal: Behavioral and Brain Sciences (2004)

The authors attempt to explain the ubiquity and persistence of human religion by invoking innate, domain-specific cognitive furniture, while dismissing the potential of other approaches, such as memetics, to produce “mindful” understandings of religion. This commentary challenges the explanatory adequacy of cognitive nativism, suggesting that memetics has as much claim to utility and “mindfulness” as innate mental modules do. And why beholdest thou the mote that is in thy brother's eye, but considerest not the beam that is in thine own eye? – Matthew 7:3
Risk and Benefits of Screening Mammography—Reply
Authors: Lydia E. Pace, Nancy L. Keating
Journal: JAMA (2014)

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CD8 T cells mediate aortic allograft vasculopathy by direct killing and an interferon-?-dependent indirect pathway
Authors: A SKARO, R LIWSKI, J ZHOU, E VESSIE, T LEE, G HIRSCH
Journal: Cardiovascular Research (2004)

Allograft vasculopathy (AV) has emerged as the major obstacle to long-term survival in clinical heart transplantation. Immune events are implicated in the development of AV, but the cellular and molecular mechanisms involved remain unclear. We sought to determine whether and by what mechanism CD8(+) T lymphocytes are able to generate AV in a murine aortic allograft model.Allo-primed CD8(+) T lymphocytes were transferred into immunodeficient (RAG-1(-/-)) mouse recipients of aortic allografts. We also transferred primed CD8(+) T cells with targeted deletions of effector molecules (perforin, Fas-ligand) to determine the role of direct cytolysis (CTL) in CD8(+) T-cell-mediated AV. We determined the role of non-CTL effector mechanisms through the transfer of either wildtype or interferon-gamma (IFN-gamma)-deficient CD8(+) T cells into RAG-1(-/-) recipients of MHC class I-deficient allografts.Adoptive transfer of primed wildtype CD8(+) T lymphocytes into immunodeficient recipients of aortic allografts resulted in the development of robust AV lesions. Transfer of CD8(+) T lymphocytes with targeted deletions in CTL effector molecules resulted in reduction of AV lesion size but not abrogation. Transfer of wildtype CD8(+) T cells into recipients of MHC class I-deficient grafts resulted in a reduction in AV lesion size, while transfer of interferon-gamma-deficient CD8(+) T cells into MHC class I-deficient grafts abrogated AV.These data indicate that CD8(+) T cells mediate AV through direct cytolysis and a distinct interferon-gamma-dependent non-CTL effector pathway. Given the resistance of this cell type to conventional immunosuppression, these results may have important therapeutic implications.
Effects of intravenous adenosine on antegrade refractoriness of accessory atrioventricular connections.
Authors: C J Garratt, M J Griffith, S O'Nunain, D E Ward, A J Camm
Journal: Circulation (1991)

Several groups have suggested the use of intravenous adenosine or adenosine triphosphate in the diagnosis of regular broad complex tachycardias. However, the short half-life of these agents has precluded assessment of their effects on refractoriness of accessory connections, and their safety in preexcited arrhythmias has not been demonstrated.We examined the effects of intravenous adenosine on accessory atrioventricular (AV) connections in 30 patients with the Wolff-Parkinson-White syndrome. Intravenous adenosine (12 mg, rapid bolus) was administered to 14 patients (group 1) during continuous atrial pacing at a cycle length 20 msec below that required to cause 2:1 conduction block in the accessory connection (mean pacing cycle length 261 +/- 41 msec). After adenosine, transient 1:1 conduction occurred via the accessory connection in 12 of 14 patients, indicating a shortening of antegrade refractoriness. In three of seven patients, this effect was abolished after intravenous propranolol (0.2 mg/kg). Nineteen patients (group 2) received adenosine (0.17 +/- 0.04 mg/kg) during induced, preexcited atrial arrhythmias. The minimum RR interval during preexcited atrial fibrillation transiently decreased (252 +/- 44 msec to 224 +/- 35 msec, p less than 0.01) after adenosine, but no change in average RR interval was observed (360 +/- 59 msec to 357 +/- 60 msec, NS). The preexcited ventricular response to atrial flutter was transiently accelerated in five of eight patients (415 +/- 21 msec to 360 +/- 49 msec, p less than 0.05) due to shortening of flutter cycle length (207 +/- 10 msec to 180 +/- 24 msec, p less than 0.05). However, 2:1 accessory connection conduction was maintained in all eight patients. All effects were short lived, with the decrease in RR interval during atrial fibrillation occurring for a maximum of two RR intervals only. No patient suffered ventricular arrhythmias or hemodynamic deterioration.Adenosine shortens antegrade refractoriness of accessory AV connections, and in some patients this action is mediated by beta-adrenergic stimulation. Adenosine may cause acceleration of preexcited atrial arrhythmias, but these effects are transient and should not discourage the use of adenosine as a diagnostic agent in broad complex, regular tachycardias of uncertain origin.
Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance
Authors: Joseph Tam, Resat Cinar, Jie Liu, Grzegorz Godlewski, Daniel Wesley, Tony Jourdan, Gergő Szanda, Bani Mukhopadhyay, Lee Chedester, Jeih-San Liow, Robert B. Innis, Kejun Cheng, Kenner C. Rice, Jeffrey R. Deschamps, Robert J. Chorvat, John F. McElroy, George Kunos
Journal: Cell Metabolism (2012)
Surgery for intermittent claudication.
Authors: C V Ruckley
Journal: BMJ (1978)

report a low incidence of false-positive studies with thallium-201 imaging.The cost of the investigation (about £45 for the isotope alone) probably precludes, its use in the regular review of asymptomatic subjects.When, however, a pilot presents with atypical chest pain or an asymptomatic pilot has an equivocal ECG the demonstration of normal stress thallium-201 myocardial images may obviate the need for unnecessary coronary arteriography with its attendant risk.
A 22 year old man with persistent regurgitation and vomiting: case progression
Authors: Mark Fox, Alasdair Young, Roy Anggiansah, Angela Anggiansah, Jeremy Sanderson
Journal: BMJ (2006)

Last week ( BMJ 2006;332:) we presented the case of Mr Neville, a 22 year old student with persistent severe epigastric pain and regurgitation and vomiting after meals. Investigation suggested gastro-oesophageal reflux disease, but treatment with acid suppression and prokinetics was only partially effective and he was readmitted to hospital with persistent symptoms and weight loss.

His persistent reflux symptoms were treated aggressively with oral esomeprazole 40 mg twice daily and later with intravenous pantoprazole. This reduced his epigastric pain and heartburn but not the regurgitation and vomiting. He did not tolerate conventional antiemetics, developing a dystonic reaction with prochlorperazine and mental agitation with metoclopramide and cyclizine. Regular ondansetron reduced the sensation of nausea but did not prevent …
CONGENITAL APHAKIA AND IRIDEREMIA.
Authors: FLAVEL B. TIFFANY
Journal: JAMA (1900)

Congenital aphakia is an exceeding rare anomaly, and is usually accompanied with other serious defects of the eye. The cases I report are of two brothers, aged 21 and 10, who visited my office Feb. 23, 1899. Advised to see me by Dr. Waterman, of Wilson, Kans., they were brought by an older brother who was perfectly emmetropic, with vision of 20/20 of each eye. This brother stated that there were seven children in the family, three of whom, one sister and these two brothers, had some trouble with their eyes; also that the mother had the same affection. An examination showed an involuntary oscillation of the globe—nystagmus of the lateral rotary form—also a gelatinous trembling or vibration of the iris—iridodonesis. The pupils were decentered toward the nasal and inferior quadrant, and would only slightly respond to the mydriatic. There was no history of consanguinity, but one of inheritance from