tbuckley/cabot-search huggingface dataset:
Further Observations upon the "Derby-Shire Neck"
Authors: W. Webb
Journal: BMJ (1886)

IN a paper read some years ago before the Midland Branch, I gave a tabulated statement of the various forms of bronchocele met with in a practice of many years in a goitrous district The close connection betweeii the goitrous mother and the cretin child was in that paper clearly established; but }Iow to account for the connection remained then, as I believe it remains now, a matter of mystery and speculateoi.How is it that a sharp intelligent woman with a gnt-re.niarried to a man of equal intelligence, has a child who becomes a -retin; whilst other children of the same parents are not wanting eitner in physical or mental power; or, to speak more definitely, how is it that one or two children in a family become dwarfed both in minid and in body, having the development of the cerebro-spinal centres arrested, and assume the form of funny little ereatures, even when beyond the period of puberty, looking prematurely old, and having thick bony skulls and expressionless faces I I have a family in my recolleetion at this moment, consisting of a man and his wife (since dead) having a large fibrous gottre.Both are of average mental eapacity.They have some sharp children, and also two cretin women, their-offspring.These latter, in age between 20 and 36, are stunted growth, and have but limited powers of understanding, or even of going to and fro, except in the shuffling gt of the paralytic.They sit from morning till night, nursing a oil, or other toy, and comport.ing themselves as very little children do, but with only a fractional part of their intelligence.Here is a representation of one of these cunous little creatures.This is a ca for " collective investigation;" but the investigation must be quick, or before it comes, bronchocele aind cretinism, as I shall hereafter ex lain, will be gone.In discusing the various plans of treatment for the lessening or removal of the enlarged thyroid body, I mentioned, in the paper before alluded to, the very limited experience I had had in the treatmenit of fibrouis goittre by the injection into its substance of the tincture of iodine, a practice which I learned from a very able paper read at King's College somne years ago by Dr. Morell bMackenzie.I have nou- used this plan of treatment in sixteen cases, aud niot, I think, with any very splendid results-results in nio way superior to the ordinary treatment by the old iodiine paint applied externally, and the internal administration of either the iodide of potassium or the iodide of iron.Thus, of these sixteen cases, in seven there was complete reduction
Different Patterns of Expansion/Contraction During the Evolution of an mtDNA Simple Repeat
Authors: Neil Howell, Corinna Herrnstadt, David A. Mackey
Journal: Molecular Biology and Evolution (2001)

*Departments of Radiation Oncology and Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas; †MitoKor, San Diego, California; and ‡Centre for Eye Research Australia, University of Melbourne, Australia; Royal Victorian Eye and Ear Hospital, Melbourne, Australia; and the Menzies Centre for Population Health Research, University of Tasmania, Hobart, Tasmania, Australia
The influence of three 48-hour dietary protocols on metabolic parameters during the maximal incremental treadmill test
Authors: Martina Čanaki, Lana Ružić, Goran Leko
Journal: British Journal of Sports Medicine (2011)

Introduction There are no protocol recommendations per-taining to nutrition before the performance assessment. The aim of this study was to determine the influence of three vari-ous 48-hour dietary protocols on parameters obtained during three trials of the maximal incremental treadmill test. Methods Thirteen physically active subjects (age: 25.73±3.09) underwent all-out treadmill test using a breath-by-breath analyzer. During the 13-day experiment, the subjects were submitted to the three controlled 48-hour dietary protocols. The obtained data were divided in three subgroups with respect to dietary conditions that prevailed during each trial. Three 48-hour dietary protocols consisted of (1) a low carbohydrate (CHO) diet 1.06 gkg-1 body mass of CHO; (2) a mixed diet 2.6 gkg-1 body mass of CHO; and (3) a high carbohydrate diet 5 gkg-1 body mass of CHO. Results The results confirmed the difference in the observed metabolic parameters after implementing the 48-hour high-carbohydrate diet. It is important to note that the metabolic indicators corresponding to the anaerobic threshold and maximal work load significantly change and reach higher values under the influence of a high-carbohydrate diet at maximal workload. Respiratory exchange ratio and blood lactate concentration contributed the most to the observed differences (p&lt;0,03). Conclusions Energy sources pertaining to different nutri-ents have to be accurately defined and balanced during both competition but also functional testing. Otherwise, errors can occur in the given physiological parameters which serve as the guidelines for planning and programming the training process, which is a precondition for maximizing the com-petition performance. An athlete, before the physiological assessment, should take approximately the same amount of carbohydrate (&gt;75%) and other nutrients, just like before a competition depending on duration and intensity of the sports activity.
SPECT Imaging in a Patient With Neuro-Behget Disease
Authors: HIROSHI MATSUDA, HIDEJI UESUGI, AKIRA YAGISHITA
Journal: Clinical Nuclear Medicine (1995)

Brain SPECT of regional cerebral blood flow using I-123 IMP demonstrated decreased perfusion in the cortex of bilateral cerebellar hemispheres in a 29-year-old man with neuro-Behçet disease. A positive correlation was obtained between the neurologic symptom of bilateral cerebellar ataxia and the SPECT finding. MRI revealed small foci with high signal intensity on T2 weighted images particularly around the cerebral peduncles and in the pons. Brain perfusion SPECT and MRI play complementary roles in analysis of areas with altered central nervous system function and pathomorphologic changes in neuro-Behçet disease.
Opiate toxicity after self poisoning with aspirin and codeine.
Authors: P J Leslie, E H Dyson, A T Proudfoot
Journal: BMJ (1986)

2 observations de tentatives de suicide au moyen de comprimes obtenus facilement sans prescription, contenant 300 mg d'aspirine et 8 mg de codeine. C'est la toxicite de la codeine qui pose des problemes dans ces cas de doses elevees (100 et 80 comprimes). Dans les 2 cas efficacite du traitement par naxolone
Abstract 3944: Serine phosphorylation of vasodilator-stimulated phosphoprotein regulates the tumorigenic potential of colon cancer cells.
Authors: Mehboob Ali, Inna Chervoneva, Giovanni M. Pitari
Journal: Cancer Research (2013)

Abstract Colorectal cancer is one of the most common and deadly cancers in developed nations. Molecular mechanisms precisely defining colorectal tumorigenesis and cancer progression remain unclear, an obstacle for innovative research applications. The vasodilator-stimulated phosphoprotein (VASP) is an actin-binding protein which critically regulates the cytoskeleton and its dependent functions, including cell shape, adhesion and migration. Of relevance, VASP Ser phosphorylation becomes deregulated in colorectal transformation and promotes invasive protrusion dynamics. Here, VASP Ser phosphorylation was selectively inhibited in colon carcinoma cells employing dominant negative mutants. Effects on cell tumorigenic potential were examined with two mouse models of colorectal cancer. Compared to control conditions, suppression of VASP Ser239 phosphorylation resulted in an enhanced cancer cell capability to establish tumor colonies in both the subcutaneous and peritoneal xenograft model. Increased tumorigenicity reflected, in part, hyper proliferative kinetics of cancer cells bearing VASP Ser239 mutants, which exhibited accelerated growth and DNA synthesis rates. In contrast, selective inhibition of VASP Ser157 slowed cell proliferation and reduced the in vivo tumorigenic potential of colon carcinoma cells, compared to respective controls. These observations support the suggestion that VASP Ser phosphorylation represents a fine signaling mechanism to control intestinal tumorigenesis and invasion, a novel paradigm for targeted anticancer strategies in patients with colorectal cancer. Citation Format: Mehboob Ali, Inna Chervoneva, Giovanni M. Pitari. Serine phosphorylation of vasodilator-stimulated phosphoprotein regulates the tumorigenic potential of colon cancer cells. [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 3944. doi:10.1158/1538-7445.AM2013-3944
Childhood cancer and proton beam therapy
Authors: A. Glaser, J. Nicholson, R. Taylor, D. Walker
Journal: BMJ (2014)

Promising new treatments need a strong evidence base

Survival of UK children with cancer is showing sustained improvement, with the proportion of under 15s living five years after diagnosis now at 82%.1 With more young people facing the prospect of long term cure, focus has moved from “cure at all cost” to “the cost of cure.” This is particularly important in brain tumours, as they account for nearly a quarter of all cancers in this age group. Although cure rates have improved, these cancers are the commonest cause of deaths from cancer in children, and 60% of survivors are moderately or severely disabled.2 Novel therapeutic strategies are being introduced in the hope of increasing survival rates while maximising the quality of resultant long term survival. Proton beam therapy, the focus of much recent discussion, is one such strategy.

The case of Ashya King has highlighted the immense pressure that develops for children, their parents, and their treating teams when dealing with the complex clinical management of brain tumours.3 Working closely and effectively with parents in the best interests of the ill child is an overwhelming priority for clinical teams. When communication breaks down, the consequences can be profound, as noted by the medical director of Southampton General Hospital.4 This underlines the importance …
Abstract 1754: A pharmacokinetics/pharmacodynamics study of sequence specificity of the PARP inhibitor, olaparib (O) with carboplatin (C) in recurrent women's cancers NCT01237067
Authors: Jung-min Lee, John Hays, Christina M. Annunziata, Lori Minasian, JoAnne Zujewski, Jennifer Squires, Deborah Nielsen, Nicole Houston, David Moorshead, Mario Cedillo, Elise C. Kohn
Journal: Cancer Research (2012)

Abstract Background: C, O, and C+O have documented activity in BRCA1/2mut+ or BRCA-like breast and ovarian cancers (Br/OvCa). The effect of drug sequence on DNA damage and cell death is unknown. Our in vitro modeling suggests that exposure to O prior to C (O&amp;gt;C) reduced double stranded DNA damage and cell loss. Our trial tests the hypothesis that C&amp;gt;O causes more cellular injury. Methods: Eligible pts have recurrent women's cancers, good end organ function, and evaluable disease. A 3+3 dose escalation run-in defined the O tablet dose in combination with C (AUC 4). The study will now randomize pts to schedule A or B (below), allowing intra-pt and inter-cohort analysis of PK/PD endpoints. PBMCs will be collected C1/2 for measurement of platination and DNA damage/repair; DNA repair protein integrity will be assessed on archival tissues. Clinical benefit, response frequency and duration, and toxicity will be ascertained. Mutation carriers will undergo progression biopsy for analysis of BRCA1/2 re-expression mutations. Results: The phase I portion is complete. 12 women (8Ov/3Br/1Endometrial[En]) have been accrued on 3 dose levels (DLs). Median prior number of regimens was 5. No DLT have been seen in 5 evaluable pts on DL3 (O tablet 200mg q12h/C AUC4 [1 pt pending]). Gr3 AEs included neutropenia (44%), and gr2 were anemia (56%), fatigue (22 %), C hypersensitivity (22%), thrombocytopenia (11%), and nausea (11%). 1 pt (DL2; stable disease) died of unrelated bleeding during C4. Clinical benefit has been observed in 8 evaluable pts with PR in 2 BRCA1mut+ OvCa (9+, 11+ mo), stabilization &amp;gt; 4mo in 6 pts (4OvCa,1BrCa, 1EnCa), and 3 are TETE. Conclusions: O in tablet formulation at 200mg q12h x 7d with C AUC4 q21d is active and tolerable, with observed interactive marrow suppression. Subsequent women will be randomized to examine schedule dependence of activity and toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1754. doi:1538-7445.AM2012-1754
Uncoupling between Epidermal Growth Factor Receptor and Downstream Signals Defines Resistance to the Antiproliferative Effect of Gefitinib in Bladder Cancer Cells
Authors: Wassim Kassouf, Colin P.N. Dinney, Gordon Brown, David J. McConkey, Alan J. Diehl, Menashe Bar-Eli, Liana Adam
Journal: Cancer Research (2005)

Abstract Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways, such as phosphatidylinositol-3 kinase/Akt and Ras/mitogen-activated protein kinase (MAPK), have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the urogenital tumors. To investigate the mechanism of resistance to EGFR inhibition in bladder cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-3β (GSK-3β). We found that the resistance to the antiproliferative effects of gefitinib, in vitro as well as in vivo in nude mice models, was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-3β activation and degradation of its target cyclin D1 were indicators of a high cell sensitivity to gefitinib. Further analysis of one phenotypic sensitive (253J B-V) and resistant (UM-UC13) cell lines revealed that platelet-derived growth factor receptor-β (PDGFRβ) activation was responsible for short circuiting the EGFR/MAPK pathway for mitogenic stimuli. However, invasion as well as actin dynamics were efficiently reduced by EGFR inhibition in UM-UC13. Chemical disruption of signaling pathways or of PDGFR kinase activity significantly reduced the inactive pool of cellular GSK-3β in UM-UC13 cells. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in bladder cancer. Although this uncoupling may arise through different mechanisms, we suggest that the resistance of bladder cancer cells to EGFR blockade can be predicted early in the course of treatment by measuring the activation of GSK-3β and of nuclear cyclin D1.
Reducing Health Risks from Indoor Exposures in Rapidly Developing Urban China
Authors: Yinping Zhang, Jinhan Mo, Charles J. Weschler
Journal: Environmental Health Perspectives (2013)

Over the past two decades there has been a large migration of China's population from rural to urban regions. At the same time, residences in cities have changed in character from single-story or low-rise buildings to high-rise structures constructed and furnished with many synthetic materials. As a consequence, indoor exposures (to pollutants with outdoor and indoor sources) have changed significantly.We briefly discuss the inferred impact that urbanization and modernization have had on indoor exposures and public health in China. We argue that growing adverse health costs associated with these changes are not inevitable, and we present steps that could be taken to reduce indoor exposures to harmful pollutants.As documented by China's Ministry of Health, there have been significant increases in morbidity and mortality among urban residents over the past 20 years. Evidence suggests that the population's exposure to air pollutants has contributed to increases in lung cancer, cardiovascular disease, pulmonary disease, and birth defects. Whether a pollutant has an outdoor or an indoor source, most exposure to the pollutant occurs indoors. Going forward, indoor exposures can be reduced by limiting the ingress of outdoor pollutants (while providing adequate ventilation with clean air), minimizing indoor sources of pollutants, updating government policies related to indoor pollution, and addressing indoor air quality during a building's initial design.Taking the suggested steps could lead to significant reductions in morbidity and mortality, greatly reducing the societal costs associated with pollutant derived ill health.
Enhanced synthesis of cholesterol and its precursors in jejunal mucosa in coeliac disease.
Authors: M Vuoristo, T A Miettinen
Journal: Gut (1986)

Patients with coeliac disease have a greatly enhanced whole body synthesis of cholesterol, but its origin is not known. In this paper the synthesis and concentrations of cholesterol and its precursors, squalene and methyl sterols, were studied in jejunal biopsies from healthy volunteers and adult patients with coeliac disease. The incorporation rates of 14C-acetate and 3H-mevalonate into non-saponifiable lipids (sum of squalene, methyl sterols and cholesterol) were increased 14 and six times in the damaged mucosa, respectively. The cyclisation rate of mucosal squalene and the conversion of squalene to cholesterol were also increased, indicating that cholesterol synthesis was activated before mevalonate, probably at the step of HMG-CoA reductase, and also after mevalonate and squalene. The steps from squalene to cholesterol were apparently not rate limiting because the mucosal concentrations and the percentage distribution of squalene and sterols were similar in the patients and in the controls. A positive correlation of the cholesterol synthesis with the number of crypt cells, suggests that the expanded crypt cell population contributed to the enhanced intestinal cholesterologenesis. Furthermore, the serum cholesterol level was negatively correlated with the 14C- and 3H-counts in the mucosal cholesterol and with the cyclisation rate of squalene probable signs of regulatory role of serum low density lipoprotein cholesterol in intestinal cholesterol synthesis. Consequently, provided that the synthesis of mucosal cholesterol is as high in vivo as in vitro it could contribute to the highly increased overall synthesis of cholesterol in the patients with coeliac disease.
Evaluation of the protective Effect of a New ?-Agonist, KWD 2131, On Allergen-Induced Bronchospasm
Authors: Birgitta Hegardt, Olle Löwhagen, Nils Svedmyr
Journal: Allergy (1980)

The selective anti-allergic effect of a new beta-agonist, KWD 2131, in inhibiting allergen-provoked asthma was compared with that of placebo in a double-blind crossover study. Non-bronchodilating doses were given by inhalation to 12 asymptomatic patients with extrinsic asthma. KWD 2131 showed a marginal anti-allergic effect. A significantly better effect than that with placebo was obtained at only one time of measurement after challenge (P < 0.05). The reproducibility of the allergen challenge was also evaluated. The mean maximum decrease in FEV1 during three different allergen-challenge procedures was 37, 31, and 38%, respectively. The difference was not statistically significant.
Treatment of Skin Carcinoma of the Face and Neck-Reply
Authors: Chahin M. Chahbazian
Journal: JAMA (1981)

In Reply.—  It appears that Dr Lindsay has misconceptions about radiation therapy in the treatment of any form of cancer, and more particularly, in the treatment of carcinomas of the skin. There are great differences in the manner in which radiotherapy may be administered; such differences affect not only the choosing of the proper equipment and filtration, but also especially affect the time-dose factors. Judgment of results cannot be made on the assumption that any practice is comparable with another. If one were to base one's judgment on Dr Lindsay's experience, one would have to agree with him. What we have presented is evidence that skillful irradiation, using filtered radiations adequately fractionated over several weeks of daily irradiation, results not only in easy and constant control of carcinomas, but, in addition, in the best conservative and aesthetic results. That Dr Lindsay has not been privileged to observe these possibilities is
ERK1/2 and p38α/β Signaling in Tumor Cell Quiescence: Opportunities to Control Dormant Residual Disease
Authors: Maria Soledad Sosa, Alvaro Avivar-Valderas, Paloma Bragado, Huei-Chi Wen, Julio A. Aguirre-Ghiso
Journal: Clinical Cancer Research (2011)

Systemic minimal residual disease after primary tumor treatment can remain asymptomatic for decades. This is thought to be due to the presence of dormant disseminated tumor cells (DTC) or micrometastases in different organs. DTCs lodged in brain, lungs, livers, and/or bone are a major clinical problem because they are the founders of metastasis, which ultimately kill cancer patients. The problem is further aggravated by our lack of understanding of DTC biology. In consequence, there are almost no rational therapies to prevent dormant DTCs from surviving and expanding. Several cancers, including melanoma as well as breast, prostate, and colorectal carcinomas, undergo dormant periods before metastatic recurrences develop. Here we review our experience in studying the cross-talk between ERK1/2 and p38α/β signaling in models of early cancer progression, dissemination, and DTC dormancy. We also provide some potential translational and clinical applications of these findings and describe how some currently used therapies might be useful to control dormant disease. Finally, we draw caution on the use of p38 inhibitors currently in clinical trials for different diseases as these may accelerate metastasis development.
Erratum: “Corticosteroids for acute chest syndrome in children with sickle cell disease: Variation in use and association with length of stay and readmission” by Sobota et al., <i>Am J Hematol</i> 2010 DOI number 21565
Authors: Amy Sobota, Dionne A. Graham, Matthew M. Heeney, Ellis J. Neufeld
Journal: American Journal of Hematology (2010)

In the above mentioned article, a citation was inadvertently dropped. The following line in the Introduction, “A later retrospective study of 65 patients (129 episodes of ACS) reported a 20-times higher odds ratio of readmission within 14 days following corticosteroid treatment even after adjusting for other confounders [6],” should refer to the article: Strouse JJ, Takemoto CM, Keefer JR, Kato GJ, Casella JF. Corticosteroids and increased risk of readmission after acute chest syndrome in children with sickle cell disease. Pediatr Blood Cancer 2008;50(5):1006-12. We apologize for any confusion that this may have caused.
Chemical reactions of organic compounds on clay surfaces.
Authors: Y Soma, M Soma
Journal: Environmental Health Perspectives (1989)

Chemical reactions of organic compounds including pesticides at the interlayer and exterior surfaces of clay minerals and with soil organic matter are reviewed. Representative reactions under moderate conditions possibly occurring in natural soils are described. Attempts have been made to clarify the importance of the chemical nature of molecules, their structures and their functional groups, and the Brönsted or Lewis acidity of clay minerals.
Mr. H. E. Powell
Authors: W. Bulloch
Journal: BMJ (1934)

ills or ignorancewhich was always so abundantly offered.His courage and indomitable will would not spare himself; his skill and knowvledge (a generation in advance of his time), enthusiasm and sympathv made him continually and seilf-sacrificingly give all.We who have had the privilege of knowing him will always treasure a very blessed memory of this unassuming and most beloved physician.His contributions to medical knowledge are so well