tbuckley/cabot-search huggingface dataset:
Ketogenic Diet in Childhood Epilepsy
Authors: J. Gordon Millichap
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The value of the ketogenic diet in the treatment of some refractory epilepsies in children is well established, but the mechanism of action is not clearly defined. Some authors have equated the beneficial effect with the degree of ketosis whereas others have stressed the importance of acidosis and diuresis. In an article in a recent issue of the<i>Archives of Neurology</i>(<b>15</b>:177, 1966), Dr. Anatole S. Dekaban reports an elevation of lipids in the plasma of 11 children with seizures benefitted by the diet and advocates repeated determinations of plasma lipids as an index of the response to therapy. Previous studies of the mechanism of anticonvulsant action of the ketogenic diet (Millichap, J.G.; Jones, J.D.; and Rudis, B.P.:<i>Amer J Dis Child</i><b>107</b>:593, 1964; and Millichap, J.G., and Jones, J.D.:<i>Epilepsia</i><b>5</b>:239, 1964) have shown that control of seizures may be obtained without significant
Physical Activities and Rheumatic Heart Disease in Asymptomatic Patients
Authors: Alvan R. Feinstein
Journal: JAMA (1962)

The influence of physical activity on the progression of rheumatic heart disease has been studied in 216 patients who were followed for an average of 21 years after an attack of acute rheumatic fever. The objective cardiac status became worse in 26 (12%), better in 50 (23%), and unchanged in 140 (65%) of the entire group. These percentages remained essentially the same when patients were divided according to the presence or absence of restrictions during school, outside of school, or in later postscholastic life. Although physical restrictions brought no cardiac benefits to asymptomatic patients, one significant effect was apparent: adverse psychosocial reactions developed in 34% of the 141 patients who were restricted in school activities, but only in 6% of the 75 who were unrestricted.
Obstructive sleep apnoea: time for a radical change?
Authors: C. L. Phillips, R. R. Grunstein
Journal: European Respiratory Journal (2006)

Reactive oxygen species (ROS) are highly reactive molecules that originate from both (intra- and extracellular) endogenous sources and from exogenous sources. They can be broadly divided into free radicals and nonradical reactive species; Stocker and Keaney 1 have examined this in a more extensive review. In the basal state, ROS play an essential physiological role in cellular signalling pathways and transcriptional regulation, which act to maintain cellular homeostasis 2. In contrast, oxidative stress is characterised by an excess of ROS, which can ultimately result in cellular injury via reactions with proteins, nucleic acids and lipids. As such, oxidative stress is hypothesised to play a primary role in the development of many disease processes, including atherosclerosis.

The oxidative modification hypothesis of atherosclerosis centres on the well-known association between low-density lipoprotein (LDL) cholesterol and atherosclerosis and, in particular, on the uptake of oxidised LDL by macrophages within the arterial wall to form foam cells, the earliest stage in atherogenesis. In addition to inflammatory cells, there are a number of vascular cell types, including vascular smooth muscle cells, endothelial cells and adventitial fibroblasts, which all provide a source of oxidants within the vessel wall and could play a role in the conversion of LDL into its oxidised (high-uptake) form. The metabolic and enzymatic sources of ROS include (but are not limited to) nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, nitric oxide synthase, myeloperoxidase, lipoxygenase and mitochondrial respiration 1 …
Is depression overdiagnosed? Yes
Authors: Gordon Parker
Journal: BMJ (2007)

We previously demonstrated that IL-7 is produced by intestinal goblet cells and is essential for the persistence of colitis. It is well known, however, that goblet cells are decreased or depleted in the chronically inflamed mucosa of animal colitis models or human inflammatory bowel diseases. Thus, in this study, we assess whether intestinal IL-7 is surely required for the persistence of colitis using a RAG-1/2<sup>−/−</sup> colitis model induced by the adoptive transfer of CD4<sup>+</sup>CD45RB<sup>high</sup> T cells in combination with parabiosis system. Surprisingly, both IL-7<sup>−/−</sup> × RAG-1<sup>−/−</sup> and IL-7<sup>+/+</sup> × RAG-1<sup>−/−</sup> host mice developed colitis 4 wk after parabiosis to a similar extent of colitic IL-7<sup>+/+</sup> × RAG-1<sup>−/−</sup> donor mice that were previously transferred with CD4<sup>+</sup>CD45RB<sup>high</sup> T cells. Of note, although the number of CD4<sup>+</sup> T cells recovered from the spleen or the bone marrow of IL-7<sup>−/−</sup> × RAG-1<sup>−/−</sup> host mice was significantly decreased compared with that of IL-7<sup>+/+</sup> × RAG-1<sup>−/−</sup> host mice, an equivalent number of CD4<sup>+</sup> T cells was recovered from the lamina propria of both mice, indicating that the expansion of CD4<sup>+</sup> T cells in the spleen or in the bone marrow is dependent on IL-7, but not in the lamina propria. Development of colitis was never observed in parabionts between IL-7<sup>+/+</sup> × RAG-1<sup>−/−</sup> host and noncolitic IL-7<sup>−/−</sup> × RAG-1<sup>−/−</sup> donor mice that were transferred with CD4<sup>+</sup>CD45RB<sup>high</sup> T cells. Collectively, systemic, but not intestinal, IL-7 is essential for the persistence of colitis, suggesting that therapeutic approaches targeting the systemic IL-7/IL-7R signaling pathway may be feasible in the treatment of inflammatory bowel diseases.
Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie
Authors: Timo Imbach, Barbara Schenk, Els Schollen, Patricie Burda, Andreas Stutz, Stephanie Grünewald, Nicola M. Bailie, Mary D. King, Jaak Jaeken, Gert Matthijs, Eric G. Berger, Markus Aebi, Thierry Hennet
Journal: Journal of Clinical Investigation (2000)

Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndromes, lead to diseases with variable clinical pictures. We report the delineation of a novel type of CDG identified in 2 children presenting with severe developmental delay, seizures, and dysmorphic features. We detected hypoglycosylation on serum transferrin and cerebrospinal fluid beta-trace protein. Lipid-linked oligosaccharides in the endoplasmic reticulum of patient fibroblasts showed an accumulation of the dolichyl pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in these patients. Accordingly, 2 mutant alleles of the DolP-Man synthase DPM1 gene, 1 with a 274C>G transversion, the other with a 628delC deletion, were detected in both siblings. Complementation analysis using DPM1-null murine Thy1-deficient cells confirmed the detrimental effect of both mutations on the enzymatic activity. Furthermore, mannose supplementation failed to improve the glycosylation status of DPM1-deficient fibroblast cells, thus precluding a possible therapeutic application of mannose in the patients. Because DPM1 deficiency, like other subtypes of CDG-I, impairs the assembly of N-glycans, this novel glycosylation defect was named CDG-Ie.
Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region- containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma
Authors: Jian Zhao, Guobin Wu, Fangfang Bu, Bin Lu, Anmin Liang, Lei Cao, Xin Tong, Xin Lu, Mengchao Wu, Yajun Guo
Journal: Hepatology (2009)

The ankyrin-repeat–containing, SH3-domain–containing, and proline-rich-region–containing protein (ASPP) family of proteins regulates apoptosis through interaction with p53 and its family members. This study evaluated the epigenetic regulation of ASPP1 and ASPP2 in hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) and explores the effects of down-regulation of ASPP1 and ASPP2 on the development of HCC. HCC cell lines and tissues from HCC patients were used to examine the expression and methylation of ASPP1 and ASPP2. The expression of ASPP1 and ASPP2 was diminished in HCC cells by epigenetic silence owing to hypermethylation of ASPP1 and ASPP2 promoters. Analyses of 51 paired HCC and surrounding nontumor tissues revealed that methylation of ASPP1 and ASPP2 was associated with the decreased expression of ASPP1 and ASPP2 in tumor tissues and the early development of HCC. Moreover, ASPP2 became methylated upon HBV x protein (HBx) expression. The suppressive effects on tumor growth by ASPP1 and ASPP2 were examined with RNA interference-mediated gene silence. Down-regulation of ASPP1 and ASPP2 promoted the growth of HCC cells in soft agar and in nude mice and decreased the sensitivity of HCC cells to apoptotic stimuli. Conclusion: ASPP1 and ASPP2 genes are frequently down-regulated by DNA methylation in HBV-positive HCC, which may play important roles in the development of HCC. These findings provide new insight into the molecular mechanisms leading to hepatocarcinogenesis and may have potent therapeutic applications. (HEPATOLOGY 2010;51:142–153.)
Validation of a live animal model for training in endoscopic hemostasis of upper gastrointestinal bleeding ulcers
Authors: M. Camus, P. Marteau, M. Pocard, C. Bal dit Sollier, A. Lavergne-Slove, A. Thibault, S. Lecleire, A. Vienne, B. Coffin, L. Drouet, X. Dray
Journal: Endoscopy (2013)

The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis.Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale).A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques.The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.
Royal college calls for 11% of NHS budget to reach primary care by 2017
Authors: G. Iacobucci
Journal: BMJ (2014)

<h3>Abstract</h3> Synthetic biological gene networks are typically conceptualized and visualized as static graphs with nodal and edge dynamics that are time invariant. This conceptualization of biological programming stands in stark contrast to the transient nature of biological dynamics, which are driven by labile biomolecules. Here we demonstrate the use of dynamical structure function theory to evaluate and visualize network dynamics within synthetic biological circuits. We introduce the theory of dynamical structure functions as a tool for understanding network dynamics in synthetic gene networks. We show in particular, that canonical biological crosstalk and resource loading effects in synthetic biology can be quantified directly using dynamical structure functions from simulation and experimental data. We illustrate the importance of knowing these loading effects through several example systems, showing that crosstalk imbalance in feed-forward loops can explain circuit failure or performance limitations. Finally, we show how dynamical structure functions can be used to diagnose crosstalk and network imbalance to explain failure modes in two types of synthetic biocircuits: an <i>in vitro</i> genelet repressilator and an <i>E. coli</i> based transcriptional event detector. We show that dynamical structure functions can be used as a form of inverse modeling, to pinpoint biological parts within a complex biological circuit that need revision or improvement.
Effects on asylum seekers of ill treatment in Zaire
Authors: M R Peel
Journal: BMJ (1996)

To describe the health effects of the political system in Zaïre on asylum seekers seen at the Medical Foundation for the Care of Victims of Torture a retrospective study was performed of the records of 92 asylum seekers from Zaïre who were seen for medical reports at the medical foundation in 1993 and 1994. Eighty one had been imprisoned; the others had been severely treated at home by the security services. Sixty six had been detained for up to one year. Prison conditions were invariably unsanitary, and food of poor quality when provided. All had been beaten on arrest, and all but two had been beaten repeatedly in prison. Nearly all the women and some of the men described sexual abuse. Almost all left prison through bribery or because a guard had a similar background. Seventy two asylum seekers had scarring, consider to be consistent with the history, and 70 were considered to have suffered persistent psychological damage. Asylum seekers from Zaïre will have health effects from experiences unimaginable to the ordinary Briton. An understanding of the background will help clinicians manage them.
Abstract 3228: Dual HER2 and EGFR inhibitor BIBW2992 have dramatic activity in a HER2 wild type/EGFR L858R murine lung cancer model
Authors: Danan Li, Zhao Chen, Liang Chen, Mei-chih Liang, Zandra Walton, Benjamin Sanofsky, Pasi Janne, Kwok-Kin Wong
Journal: Cancer Research (2010)

Abstract Dual HER2 and EGFR inhibitor BIBW2992 have dramatic activity in a HER2 wild type/EGFR L858R murine lung cancer model HER2 (ERBB2) is a proto-oncogene that belongs to EGFR tyrosine kinase receptor family. HER2 genomic locus amplification and HER2 protein over-expression detected by IHC have been identified in many human cancer types including breast, brain and lung cancer. Simultaneous over-expression of both HER2 and EGFR occurs in a subpopulation of lung cancer patients. Here we developed a transgenic mouse model with inducible wild type HER2 expression in type II pneumocyte. Continual HER2 over-expression in the lung epithelial compartment leads to peripheral lung adenocarcinoma that responds dramatically to targeted anti-HER2 therapeutics. Mice over-expressing both EGFR L858R and the wild type HER2 alleles do not significant accelerate tumorigenesis or alter of tumor histology as compared to tumors generated by the wild type HER2 single alleles. The HER2/EGFR driven murine lung tumors showed mild and transient response to the EGFR inhibitor, gefitinib. This result mimics the observation from clinical patients. However, the dual HER2/EGFR inhibitor, BIBW2992, is much more effective against these HER2/EGFR driven lung cancers as measured by tumor regression and over all survival. Our data suggested that targeting therapy against both EGFR and HER2 is a better strategy in lung cancer patients with co-expression of EGFR and HER2 when compared with treatment against EGFR alone. Clinical trial for dual HER2/EGFR inhibitors in this population should be considered. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3228.
The Abuse of Coronary Arteriography
Authors: Brendan Phibbs
Journal: New England Journal of Medicine (1979)

IT has been well observed that by solving one problem one usually creates the next. Coronary arteriography is a current example of the solution-turned-problem, since the procedure by its character slips through the net of controls designed by the medical profession to protect the public. Coronary arteriography, of course, is a superb diagnostic technique that, when done under appropriate circumstances by competent physicians, can yield enormously useful information with minimal and quite acceptable morbidity and mortality. However, when one considers that no tissue is removed for review, that the indications for the procedure are not well defined and are often . . .
Principles of Medical Therapy in Pregnancy
Authors: Edwin M. Gold
Journal: JAMA (1986)

Here is a truly extraordinary encyclopedic textbook of internal medicine written expressly for both practicing obstetricians and internists. The underlying theme of this modern reference work stresses medical management during pregnancy (taking into account both mother and fetus), as opposed to medical practices during the nonpregnant state. To present a review of this text within the editorial limitations of conciseness is analogous to trying to cram a whale into a sardine can. Edited by Dr Gleicher with the able assistance of six coeditors, this is a volume of 1,290 pages, encompassing 191 chapters, authored by 152 contributors (of whom 71 are obstetric specialists and 81 are specialists in the wide variety of medical entities presented), and with a 55-page index. Despite the diversity of authorship, the text is elegantly homogeneous in style. All organ systems and their relevant diseases adversely affecting mother and fetus are discussed in depth, and each
Adverse events associated with infliximab therapy in a large single centre UK cohort
Authors: M. Sprakes, P. J. Hamlin, L. Warren, D. Greer, A. C. Ford
Journal: Gut (2011)

<h3>Introduction</h3> Long term safety data for biologic therapies in Crohn9s disease (CD) is still emerging. A recent study has suggested that serious adverse events occur in 15% of patients receiving infliximab (IFX) therapy for CD, and more frequently in patients on concomitant immunosuppression. However, the TREAT registry observed no increased risk of adverse events with IFX, compared to other therapies. The authors assessed adverse events in patients who have received IFX therapy for CD at their referral centre. <h3>Methods</h3> All patients who receive IFX therapy for CD in our referral centre for CD were included on a prospective database. Data stored included sex, age at diagnosis, duration of disease, previous surgical history, smoking history and Montreal classification. Response and remission data are also prospectively recorded. Adverse events to infliximab are documented each time a patient attends for an infusion, or at the following clinic visit. Patients who were not receiving concomitant immunosuppression were premedicated with hydrocortisone at each infusion. <h3>Results</h3> In total, 3165 IFX infusions were administered to 210 patients (median of 24 (IQR 7–48) months), mean Harvey-Bradshaw index of 9. In total, 59 (28.1%) patients experienced adverse events to IFX. 23 patients had a reaction during the infusion, with 9 discontinuing therapy. 12 patients had hypersensitivity reactions and discontinued IFX. Seven patients discontinued IFX due to psoriatiform rashes. There were 14 (6.7%) opportunistic infections (including seven episodes of Varicella zoster reactivation, and one diagnosis of pulmonary tuberculosis in a Caucasian male who had received 3 years of maintenance therapy and had a normal chest x-ray pre-IFX), 3 infections required permanent discontinuation of IFX. There were 3 malignancies (1.4%) all discontinuing IFX. One was an adenocarcinoma in a peri-anal fistula tract. Examination under anaesthesia (EUA) and biopsy pre-IFX had been non-diagnostic, but EUA was repeated after non-response to IFX. One older diabetic patient developed a fatal spindle-cell tumour, and one patient in remission had an incidental finding of a renal cell carcinoma when disease was being reassessed by imaging prior to withdrawal of IFX. Overall, 34 (16.2%) patients discontinued IFX due to adverse events. 21 (35.6%) patients were receiving concomitant immunomodulator therapy at the time of the adverse event. There was no significant difference in adverse events when comparing episodic versus maintenance therapy (p=0.62). <h3>Conclusion</h3> IFX is safe and well tolerated with low numbers of adverse events, malignancies and mortality in our large single centre cohort of patients with severe active CD. Careful patient selection, pre-IFX screening and monitoring during therapy can optimise the risk benefit ratio.
Original pack dispensing.
Authors: T P Delaney
Journal: BMJ (1987)

none) or who have been so subsidised bv the manufacturers.What would happen if everv uni- versity hospital applied the same restrictions?More worrying to me is the fact that where local National Health Service management labours under the delusion that drugs account for a considerable proportion of the overall costs of anaesthesia and intensive care a new breed of second class university department is being created.In these days of dwindling independent sources of f'unds such departments can hope to keep in the forefront only by doing investigative work that the manufacturers want to support: exeunt academic and clinical freedom, arm in arm.
Circulating immunoglobulin G1 antibody in patients with ulcerative colitis against the colonic epithelial protein detected by a novel monoclonal antibody.
Authors: A Dasgupta, A Mandal, K M Das
Journal: Gut (1994)

Autoimmunity has been implicated in the pathogenesis of ulcerative colitis (UC). Several studies have shown amplified immunoglobulin G1 (IgG1) antibody response in UC; however the immunoreactive antigen(s) is unknown. To study this antigen(s), mucosal colonic extract was prepared by sonication, ultracentrifugation followed by ion exchange chromatography in fast protein liquid chromatography. The fraction (enriched colonic peptide), that was most reactive to a novel monoclonal antibody, 7E12H12 (IgM isotype), was isolated and used to examine the immunoreactivity against the patients9 serum samples. Two hundred and thirteen coded samples from 111 patients with UC (symptomatic and untreated (63), symptomatic and treated (26), remission (22)); 47 with Crohn9s disease (CD) (40 were symptomatic and untreated, and 30 had colonic disease); 29 with acute diarrhoea caused by specific pathogen(s); 10 with systemic lupus erythematosus, and 16 normal subjects were examined against the enriched colonic peptide by IgG subtype specific enzyme linked immunosorbent assays (ELISAs). Total IgG antibody reactivity was significantly (p &lt; 0.01) higher only in symptomatic and untreated UC patients compared with each of the non-UC group, but the sensitivity was only 50%. IgG2 and IgG3 reactivities were not different among various groups. The IgG1 antibody reactivity against the enriched colonic peptide, however, differentiated UC patients from CD and each of the other non-UC groups. Seventy nine per cent of the patients with UC, treated or untreated, symptomatic or in remission, had significantly (p &lt; 0.0001) higher IgG1 antibody against the enriched colonic peptide when compared with each of the other non-UC groups. Only 12% of CD serum samples and none of the other control serum samples reacted. Using purified serum IgG1 and 7E12H12-IgM, by 7E12H12 reactive peptide indeed reacts with UC-IgG1 antibody but not with control IgG1.