tbuckley/cabot-search huggingface dataset:
Abstract 4815: Aberrant DNA hypermethylation of the ITIH5 tumor suppressor gene in acute myeloid leukemia
Authors: Christoph Oing, Edgar Jost, Edgar Dahl, Stefan Wilop, Rainhardt Osieka, Tim H. Brümmendorf, Oliver Galm
Journal: Cancer Research (2011)

Abstract Acute myeloid leukemia (AML) is a clonal disorder resulting from uncontrolled proliferation of hematopoietic stem cells. Important genetic findings in AML comprise chromosomal translocations involving different transcription factors and activating point mutations in multiple signal transduction pathways. Hypermethylation of CpG islands within gene promoter regions in collaboration with deacetylation and other modifications of histone amino acids is associated with transcriptional inactivation and represents, in addition to genetic aberrations, an important mechanism of gene silencing in the pathogenesis of human cancer. Inter-alpha-trypsine inhibitors (ITIs) are proteases consisting of one light chain (bikunin) and two heavy chains (ITIHs), which stabilize the extracellular matrix (ECM). The putative tumor suppressor gene ITIH5 has previously been reported to be downregulated in association with aberrant DNA methylation in breast cancer. In this study, we determined the methylation status of the promoter-associated CpG island of ITIH5 in hematopoietic cell lines and primary AML patient samples. Methylation specific polymerase chain reaction (MSP) analysis revealed that the ITIH5 promoter region was hypermethylated in the AML cell lines HL60 and KG1a. Treatment of cell lines that carry a hypermethylated ITIH5 gene with the demethylating agent 5-aza-2’-deoxycytidine resulted in partial promoter demethylation. We then analyzed the ITIH5 methylation status in primary mononuclear cells obtained from 110 patients with newly diagnosed AML. The frequency of aberrant methylation among the primary patient samples was 14.5 % (16/110). Among clinical prognostic parameters, we found a significant positive correlation between hypermethylation of ITIH5 and elevated serum levels of lactate dehydrogenase (LDH, p=0.013) in univariate analysis, whereas no correlation was found for cytogenetics, FAB subtype, age, white blood cell count and overall survival. We conclude that promoter hypermethylation of ITIH5 is a novel epigenetic event in AML that may contribute to leukemogenesis by interfering with the interaction between the ECM and the leukemic clone. Further studies are warranted to elucidate the functional consequences of epigenetic dysregulation of ITIH5 in leukemogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4815. doi:10.1158/1538-7445.AM2011-4815
FURTHER REPORT ON EXPERIMENTAL EVALUATION OF MENTAL HYGIENE TECHNIQUES IN SCHOOL AND COMMUNITY
Authors: BENJAMIN H. BALSER, FRED BROWN, MINERVA L. BROWN, LEON LASKI, DONALD K. PHILLIPS
Journal: American Journal of Psychiatry (1957)

A further study on experimental evaluation of controlled mental hygiene workshops in school and community is reported. This controlled study was made on mental health workshop groups of teachers and parents and controlled by other groups of teachers and parents from the same and other communities. These studies were all made in Westchester County, New York State. Psychological test instruments were used before and after the mental health workshops for both the experimental and control groups, all groups being tested simultaneously. The scoring and statistical analysis of over 110,000 test items lead to the following conclusions: 1. The experimental groups as a whole showed more changes in a positive direction than did the control groups. 2. There was a significant trend for parents in the experimental groups to show greater over-all changes than did the teachers as compared with changes in the control groups. 3. In spite of the differences in content, approach, and instructions to the experimental groups, there were no statistically significant differences between changes produced in the groups by a psychiatrist and a psychologist. 4. The most striking positive changes were obtained on the Parental Survey Scale for all the experimental groups, with 2 groups showing a conclusive change toward a more liberal conception of parent-child relationships and 1 a trend toward change(6). 5. Telling a control group that it is being used as a control seems to raise subscale scores on the Minnesota. Whether this would hold in general or whether a community factor is operating is uncertain. 6. There were no changes in Morale for any of the groups, suggesting that the morale "climate" at the time of this experiment is better than it was at the time of previous experiment or that community differences were being reflected. 7. One control group showed a significant change in parental attitudes. It is suggested that this might have resulted from the stimulus value of the Scale. 8. It is probable that the workshop is better suited for those who volunteer to participate rather than for an unselected random population. 9. It seems advisable to stress attitude evaluation in future studies rather than "adjustment." This might make it possible to administer a shorter test battery and to accomplish a more detailed item analysis of the responses.
Activation of monocytes by interferon-gamma has no effect on the level or affinity of the nicotinamide adenine dinucleotide-phosphate oxidase and on agonist-dependent superoxide formation.
Authors: M Thelen, M Wolf, M Baggiolini
Journal: Journal of Clinical Investigation (1988)

Human monocytes purified by elutriation were cultured for 3 d in Teflon bags with or without human recombinant interferon-gamma (rIFN gamma). The cells were then collected and used in suspension to determine the rate of stimulus-dependent superoxide or hydrogen peroxide formation as a measure of the NADPH-oxidase. The treatment with IFN gamma increased this rate two- to threefold when phorbol myristate acetate (PMA) was used as the stimulus. By contrast, no IFN gamma-dependent increase in superoxide production was observed when the cells were stimulated with different concentrations of the receptor agonist N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) alone or in combination with another receptor agonist, platelet-activating factor (PAF). At optimum concentrations, f-Met-Leu-Phe elicited rates of superoxide formation that could not be exceeded under other stimulatory conditions including PMA after treatment with IFN gamma. It thus appears that f-Met-Leu-Phe can lead to maximum activation of the NADPH-oxidase, and that this response is not influenced by IFN gamma. Treatment with IFN gamma also failed to affect the affinity of PMA- or f-Met-Leu-Phe-stimulated oxidase for NADPH, the Km values being 30 to 40 microM under all conditions. IFN gamma did not alter the cellular levels of cytochrome b558, as measured by low-temperature spectroscopy, and protein kinase C, as measured by [3H]phorbol dibutyrate binding, and did not appreciably influence the stimulus-dependent increase of cytosolic free calcium. These results indicate that activation of human mononuclear phagocytes by IFN gamma does not affect the level and the kinetic properties of NADPH-oxidase or its activation by receptor agonists. They confirm, however, that IFN gamma enhances the respiratory burst response to PMA.
"Batch" or "on-line" for child health
Authors: J H Bradshaw-Smith, R H Fisher
Journal: BMJ (1980)

activity (p 29; Fox et al2), a finding not con- sistent with-the data of McClusky's et al.3 Thus there is no consensus regarding the relationship between the presence or absence of HLA-B27 and disease severity in Reiter's syndrome.This is an important issue since it would appear that knowledge of HLA status does not provide the physician with useful prognostic information, a topic discussed more fully elsewhere.'
Pediatric Injuries in the Back of Pickup Trucks
Authors: Phyllis F. Agran
Journal: JAMA (1990)

Travel in the back of pickup trucks has not been adequately addressed as an occupant protection issue. This study compares injuries sustained by children riding in the back of pickup trucks with those of children riding in the cab. Data were obtained from a multihospital monitoring system and the coroner in a single urban county. The series of injured children consisted of 290 children 0 through 14 years of age, 201 of whom had been riding in the cab and 89 in the back. Age distribution of the children demonstrated that it is most frequently the 10- to 14-year-olds who travel in the back. Children riding in the back were more frequently injured in noncrash events (absence of a collision), had more ejections, had more injuries, and sustained more severe injuries as measured by the Maximum Injury Score. With increased restraint use in the cab, it is likely that even greater differentials in injury severity and patterns would be realized. Education regarding the hazards of travel in the back of pickups and stronger legislation limiting the transport of children in the back of trucks are recommended.
THE TREATMENT OF EMOTIONAL DISTURBANCES.
Authors: HOWELL T. PERSHING
Journal: JAMA (1904)

had many severe attacks of headache and has at times been confined to the bed for days with sciatica.She suffers almost constantly with an ovarian trouble, and yet she tells me that she has never had pain enough to tempt her to take morphin.While she is far from being well, she is much better than while she was using the narcotic.Case 10.-Mrs.L., age 45, addicted to morphin eight years and to cocain for six years.At the time of admission for treatment, March 4, 1898, was using about 20 grains of mor¬ phin and from 30 to 40 grains of cocain per day.I have never seen another patient that was so badly troubled with cocain hallucinations as was this one.She imagined that she could hear persons talking about her constantly, and also that these persons could see her under any and all conditions.It was almost impossible to get her to undress to go to bed, as she was sure she would be seen by these imaginary persons; for weeks she could not be induced to take off all her clothing to be given a bath.She had taken treatment at three or four institutions for the purpose of getting free of the morphin.1 am not sure whether or not she had ever been free of the drugs from the time she first began using them.Her mental condition was such that it made her an exceedingly difficult patient to care for.While she was entirely irresponsible, her cunning seemed to be more acute, and twice during her treatment she stole away, went down town and loaded herself with morphin and cocain.It was six months before I was able to get her free from the drugs.The hallucinations had grown gradually less and yet she was not entirely free from them at the time she left my institution in November.She could still hear whisperings and yet she realized that there was no person there, and understood that it would be impos¬ sible for one to be whispering and she be unable to see them.She remained in the city with a sister for two months and then went to London, England, where she visited relatives for three months.When she returned she was still annoyed with hearing whisperings, although these were all the while growing less.Up to this time she had had plenty of money.She had been married to a man of means, but two or three years previous he had deserted hei'.As a result, on her return from England she was penniless.She went to Chicago to seek em¬ ployment.Being an intelligent and bright woman with good address she soon found work.To-day she is earning a good living, is perfectly contented, and says that she never was as well and happy as she has been since being free from the addiction.
Implantation of Self-Expanding Esophageal Metal Stents for Palliation of Malignant Dysphagia
Authors: H. Neuhaus, W. Hoffmann, H. J. Dittler, H. P. Niedermeyer, M. Classen
Journal: Endoscopy (1992)

Eleven self-expanding metal stents were perorally implanted in ten patients with locally advanced malignant obstruction of the esophagus. After bougienage of the strictures, the stents were painlessly inserted and properly released by means of an 18 French gauge delivery catheter. In all cases, the endoprostheses expanded to a diameter of 14-20 mm and achieved immediate improvement of dysphagia. One perforation was seen after a single session of dilatation and subsequent stent insertion. No other early complication was observed. After a median follow-up of 74 days (Range, 33-252 days), one of eight patients is still alive and 7 died of non-procedural causes. The grade of dysphagia improved from a mean of 2.9 to a mean of 1.6 and 2.0, respectively, depending on the follow-up period (scale 0-4). Esophageal reobstruction occurred in four patients due to food impaction (two patients) or tumor ingrowth into the stent through the wire mesh (two patients). Recanalisation of the obstructed stent lumen was achieved by endoscopic irrigation (two patients), laser therapy only (one patient) or diathermia with subsequent insertion of a conventional plastic endoprosthesis into the metal stent (one patient). The initial results are promising. The delivery system, the wide-bore diameter, the macroporous configuration and the low mass of the self-expanding stents would seem to be associated with a less traumatic insertion procedure and a lower rate of stent migration as compared with conventional prostheses. Technical improvement may be required for prevention of tumor infiltration. Controlled trials are warranted to determine the future role of metallic stents for palliation of esophagocardial tumors.
Abstract 1172: Phase I study of histone deacetylase inhibitor belinostat in combination with warfarin in patients with solid tumors or hematological malignancies.
Authors: Neeraj Agarwal, Mark L. Wade, Julia Batten, Cynthia Davidson, Show-Li Sun, Sunil Sharma
Journal: Cancer Research (2013)

Abstract Background: The family of Histone Deacetylase (HDAC) enzymes serves as important epigenetic regulators of gene expression through modulation of acetylation on important histone and non-histone proteins. Aberrant acetylation of histones can alter gene expression believed to be important in the tumorigenic process. Belinostat, a potent inhibitor of HDAC proteins has demonstrated anti tumor activity in animal models and in humans. The purpose of this study was to examine the pharmacokinetic and pharmacodynamic properties of warfarin in combination with belinostat and to evaluate the safety profile of belinostat with concomitant warfarin. Methods: Eligible patients enrolled on the study received 5 mg PO warfarin 14 days prior to administration of belinostat. Belinostat was administered as an iv infusion, 1000mg/m2 over 30 minutes for 5 consecutive days every 21 days. On day 3, cycle 1 of belinostat treatment, a second dose of 5mg PO warfarin was administered 2 hours prior to belinostat. Pharmacokinetic blood samples were obtained during cycle 1 of the study to measure warfarin and belinostat metabolism. Toxicities were monitored regularly throughout treatment and response was monitored according to standard of care guidelines. Results: 18 patients, with solid tumors or hematologic malignancies, treated with belinostat and warfarin were included in this analysis. Median age was 55 years (31-77). 11 (61%) patients were male and 7(39%) patients were female. The most common Grade 1 or 2, toxicities observed during the study were anemia (78%), fatigue (72%) and nausea (61%). The most frequent Grade 3 or 4 toxicities were nausea (11%) and hyperuricemia (11%). No Grade 3 or 4 thrombocytopenia or neutropenia were reported. No treatment related Grade 5 toxicities were reported. During cycle 1 no patient experienced treatment delays or discontinued study as result of treatment related toxicity. Conclusion: Belinostat was generally well tolerated in patients with solid tumors or hematologic malignancies with the major toxicity being anemia, fatigue or nausea. Pharmacokinetic results will be presented at the conference. Citation Format: Neeraj Agarwal, Mark L. Wade, Julia Batten, Cynthia Davidson, Show-Li Sun, Sunil Sharma. Phase I study of histone deacetylase inhibitor belinostat in combination with warfarin in patients with solid tumors or hematological malignancies. [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 1172. doi:10.1158/1538-7445.AM2013-1172
AIR EMBOLISM IN ARTIFICIAL PNEUMOTHORAX
Authors: THOMAS R. JONES
Journal: JAMA (1941)

Of all the complications of artificial pneumothorax therapy, air embolism is the most alarming and most dangerous. Its occurrence is sudden and without preceding signs or symptoms, as it is in reality an accident. Its results either are instantaneous or appear in a short time. Rogers, while irrigating the empyema cavity of a small girl in 1864, observed an attack characterized by pallor, unconsciousness and clonic convulsions with recovery after twenty-four hours. While diagnosed as pleural eclampsia it may be logically assumed from the description of the attack that this was a case of cerebral air embolism. Brandes<sup>1</sup>in 1912, while attempting to outline an empyema cavity with bismuth paste, accidentally demonstrated the mechanism of air embolism. On injection of the paste, the patient became unconscious and was suddenly seized with fatal convulsions. On postmortem examination bismuth was found in the vessels of the cerebral cortex and brain stem.
SIECUS and Sex Education
Authors: Homer C. Pheasant
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The LETTERS section of the Aug 11, 1969, issue was full of "words and fury" relating to sex education in schools. It has occurred to me that much of the violent opposition, while alleging that this is a "responsibility of parents," still make no adequate provision for parent education in these matters of sex information. The children of today are the parents of tomorrow! It would seem far simpler to educate these "parents of tomorrow" along lines of family life education which would include sex information by having this carefully incorporated in all relevant courses to which they would be exposed during their elementary and high school education. To name a few: biology, psychology, economics, accounting, domestic science— yes, even perhaps manual training so the father or husband could be a "do-it-yourselfer." To duplicate this educational system so that we could educate present parents seems a rather costly
Walking for health and fitness
Authors: J. M. Rippe
Journal: JAMA (1988)

Recent studies have linked regular physical activity with reduced likelihood of developing coronary heart disease. Even low- and moderate-intensity exercise such as walking, when carried out consistently, is associated with important cardiovascular health benefits. Walking has also been shown to reduce anxiety and tension and aid in weight loss. Regular walking may help improve cholesterol profile, help control hypertension, and slow the process of osteoporosis. Recent physiological studies have demonstrated that brisk walking provides strenuous enough exercise for cardiovascular training in most adults. A recently developed submaximal 1-mile walk test provides a simple and accurate means for estimating aerobic capacity and guiding exercise prescription. These new insights and tools will assist the clinician in the prescription of safe and effective walking programs.
Infant feeding practices: a cause for concern.
Authors: J H Tripp, D E Francis, J A Knight, J T Harries
Journal: BMJ (1979)

Cases of infants with life-threatening nutritional deficiencies due to certain strict vegetarian or macrobiotic diets have recently been reported.'-7It has been suggested that in some instances this should be regarded as a form of child abuse.'We have recently come across infants who have been severely ill as a result of similar nutritionally inadequate diets.During the past 12 months nine have presented to the Hospital for Sick Children, Great Ormond Street, and six to the Queen Elizabeth Hospital for Children, Hackney Road.In these cases the parents, not themselves on exotic diets, have used alternative "milks" for infant feeding in good faith on the basis of publications or on the recommendation of those providing professional advice.We wish to draw attention to the practice of lay, professional, or commercial recommendations of what may often be inappropriate infant feeds.Most mothers interested in vegetarian and other cult diets are keen to breast-feed their infants, and it is only when this is not possible that other feeds are used.Relatively minor problems may arise when infants are in- appropriately given supplements to their basic milk feeds or when they are on mixed diets.For example, the frequent use of Complan as an addition to infant feeds has resulted in at least two referrals to this hospital of infants with uraemia, later found to be due to excessive protein intake.The manu-
Measuring the benefit of treatment: number needed to treat
Authors: P. Sedgwick
Journal: BMJ (2015)

The effectiveness of offering financial incentives to help pregnant smokers quit was investigated using a randomised controlled trial. The intervention consisted of routine care plus the offer of up to £400 (€559; $600) for women who attended specialist pregnancy stop smoking services and were abstinent from smoking at 34-38 weeks’ gestation. The control group received routine care, which included offers of face to face appointments to discuss smoking and cessation, free nicotine replacement therapy, and weekly support phone calls. The setting was a materially deprived inner city population in the west of Scotland. Participants were 612 self reported pregnant smokers aged at least 16 years and less than 24 weeks pregnant. Women were randomised to the intervention (n=306) or control (n=306).1 The primary outcome was abstinence from smoking at 34-38 weeks’ gestation. Secondary outcomes included birth weight. The proportion of smokers who were abstinent at 34-38 weeks’ gestation was significantly higher in the financial incentives group than in the control group (22.55% (n=63) v 8.58% (n=26); absolute risk difference 13.97%, 95% confidence interval 8.2% to 19.7%; P<0.001). The number needed to treat (NNT) was 7.2 (5.1 to 12.2). The relative risk of abstinence at 34-38 weeks’ gestation for the intervention group compared with the control group was 2.63 (1.73 to 4.01). No significant difference was seen between treatment groups in mean birth weight (3140 (standard deviation 600) v 3120 (590) g; P=0.67). The researchers concluded that financial incentives were effective in helping pregnant smokers quit. Which one of the following statements is the best interpretation of the NNT?
The combination of low midarm muscle circumference and high waist circumference predicted higher mortality in older men
Authors: Anna Peeters
Journal: Annals of Internal Medicine (2008)

Source Citation Wannamethee SG, Shaper AG, Lennon L, Whincup PH. Decreased muscle mass and increased central adiposity are independently related to mortality in older men. Am J Clin Nutr. 2007;86:1339-46. 17991644
DOUBLE-BLIND CONTROLLED TRIAL OF SINGLE-DOSE TREATMENT WITH BOVINE SURFACTANT IN SEVERE HYALINE MEMBRANE DISEASE
Authors: TonseN.K Raju, Rama Bhat, KristineM Mcculloch, Haruo Maeta, Dharmapuri Vidyasagar, Daniel Sobel, Mark Anderson, PaulS Levy, Sylvia Furner
Journal: The Lancet (1987)