tbuckley/cabot-search huggingface dataset:
Migraine Therapeutics in Adolescents
Authors: Haihao Sun, Eric Bastings, Jean Temeck, P. Brian Smith, Angela Men, Veneeta Tandon, Dianne Murphy, William Rodriguez
Journal: JAMA Pediatrics (2013)

OBJECTIVES To conduct a systematic review and analysis of trial data submitted to the US Food and Drug Administration (FDA) to identify possible causes for the failure of pediatric trials of triptans for treatment of migraines. DATA SOURCE The FDA website for drug information and published literature. STUDY SELECTION All pediatric efficacy and pharmacokinetics trial data of drugs used for abortive treatment of migraine submitted to the FDA from January 1, 1999, through December 31, 2011. MAIN OUTCOME MEASURES Patient demographic baseline characteristics, inclusion and exclusion criteria, trial designs, efficacy end points, and pharmacokinetic profiles were analyzed and compared across drug products. RESULTS We analyzed data for sumatriptan succinate nasal spray and zolmitriptan, eletriptan hydrobromide, almotriptan malate, and rizatriptan benzoate tablets. Seven efficacy trials had a randomized, double-blinded, placebo-controlled, parallel-group trial design. In 4 trials, patients were required to have a history of migraine attacks lasting at least 4 hours. High response rates for placebo were observed in all trials, with pain relief at 2 hours ranging from 53% to 57.5%. Nonrandomization of patients with an early placebo response design was used in the rizatriptan trial in 2011. Compared with the rizatriptan trial conducted in 1999, the 2011 rizatriptan trial reduced the placebo response rate by 6% for headache freedom at the 2-hour posttreatment end point owing to study design. The pharmacokinetic profiles between adolescents and adults were statistically similar. CONCLUSIONS High placebo response rates are consistent across all trials and may represent the principal challenge in pediatric trials of drugs for abortive treatment of migraine. Enrichment with selection of subjects with long-lasting migraine attacks is not sufficient to overcome high placebo response rates. Another enrichment strategy, the nonrandomization of patients with an early placebo response, successfully reduces the high placebo response rate for rizatriptan and is a trial design that should be considered for future pediatric trials of abortive migraine therapeutics.
Myopia and Scleral Reinforcement: A Sensitive Nerve
Authors: Frank B. Thompson
Journal: JAMA (1985)

To the Editor.—  I recently read Dr Brian Curtin's answer to Dr Pika's 1 question about his grandson who had severe bilateral high or degenerative myopia and whether there was any treatment possible.  Dr Curtin is certainly an extremely well-known and respected researcher of the pathogenesis of myopia. However, I strongly disagree with his comments directed toward scleral reinforcement for posterior staphyloma in high myopia. Dr Curtin and I have recently had an opportunity to debate this procedure at the symposium on myopia at Ohio State University in Columbus, and I feel that Dr Curtin, as I am sure he would be the first to acknowledge, represents one side of the scleral reinforcement question. He gives the impression in his letter that the operation was developed in eastern Europe, whereas it was originally developed by Dr William Borley in San Francisco more than 25 years ago and has subsequently been
Essential Role of LAT in T Cell Development
Authors: Weiguo Zhang, Connie L Sommers, Deborah N Burshtyn, Christopher C Stebbins, Jan B DeJarnette, Ronald P Trible, Alexander Grinberg, Henry C Tsay, Helena M Jacobs, Craig M Kessler, Eric O Long, Paul E Love, Lawrence E Samelson
Journal: Immunity (1999)
TCT-254 Everolimus Eluting Bioresorbable Vascular Scaffolds In Patients With ST-Segment Myocardial Infarction. Safety Feasibility and Acute Performance
Authors: Roberto Diletti, Antonios Karanasos, Takashi Muramatsu, Shimpei Nakatani, Sjoerd T. Nauta, Yoshinobu Onuma, Evelyn Regar, Carl J. Schultz, Patrick W. Serruys, Robert J. Van Geuns, Nicolas M. Van Mieghem, Felix Zijlstra
Journal: Journal of the American College of Cardiology (2013)
THE POTENCY OF ANTIPNEUMOCOCCIC SERUM
Authors: N. E. WAYSON
Journal: JAMA (1918)

Antipneumococcic serum, as developed by Neufeld, was not regarded as entirely satisfactory as a therapeutic agent. Cole and his co-workers renewed the interest in this serum, however, by their work on the differentiation of types of pneumococci and the application of the specific univalent serums.  Clinical evidence has since accumulated which tends to encourage the use of Cole's Type I serum in cases in which the corresponding type of infecting organism has been determined.  The official control of this product by protection tests has thus far been confined to serum produced by the immunization of horses against Type I pneumococci.  Polyvalent serums are required to show the same protective action against Type I organisms as is the specific type serum.  The evidences of the manufacturers' protection tests are accepted for the potency of serums made by immunizing animals against pneumococci of Types II and III.  The present method of testing
Proceedings: A re-examination of the hypoglycaemia-induced "stress" response of the hypothalamo-pituitary-adrenal axis in patients with rheumatoid arthritis on long-term adrenocorticotrophin (ACTH) therapy.
Authors: M R Fleisher, D N Glass, J R Daly
Journal: Annals of the Rheumatic Diseases (1973)

Heberden Society 595 develops concealed hostility and difficulty in demonstrat- ing feelings of aggression to people around.Is this true and do you think that this is responsible for their depres- sion ?DR.ZAPHIROPOULOS It is true that patients with chronic disability are likely to exhibit 'conflicts in the expression of hostility', but I do not know whether the anxiety and depression is a result of this; they are all part of the general disturbance seen in rheumatoid patients (Robinson, Kirk.Frye, and Robertson, 1972).
Abstract 2914: To study DNA repair function of two closely related human lung adenocarcinoma cell lines, CL1-0 and CL1-5.
Authors: Feng- Chang Wu, Yu-Fen Lin, Liang-Chuan Lai, Eric Y Chuang, Mong-Hsun Tsai
Journal: Cancer Research (2013)

Abstract Exogenous agents and endogenous processes, such as reactive oxygen species (ROS) can induce base oxidation and DNA lesions. One of the most severe DNA lesions is the double-strand break (DSB). There are several repair systems to fix the resulting DNA lesions to prevent error copies of genetic information to be carried to daughter cells. Oxidative stress is an important factor to induce DNA damage during normal cellular metabolism. In this study, we wanted to use lung cancer cells, CL1-0 and CL1-5 cells, which have differential invasiveness ability to characterize DNA repair function. Hydrogen peroxide (H2O2) was treated in lung adenocarcinoma cells to induced DNA DSB. By using immunoflurecence microscope, we found that CL1-5 had more gamma-H2AX foci (DNA DSB marker) and ROS accumulation than CL1-0 post both 1 mM and 5 mM H2O2 treatment. Moreover, CL1-0 had a tight G2/M checkpoint and has a longer G2 arrest after H2O2 treatment, but not found in CL1-5. In addition, increasing sub-G1 population (apoptotic cells) was found in H2O2-treated CL1-5 but less in CL1-0. Furthermore, phosphorylated-Akt (S473) was decreased in CL1-5, In contrast, phosphorylated-ATM (S1981) and Chk2 were increased after 5 mM H2O2 treatment for 90 min. In addition, the level of GSH was persistently lower at the steady state and post H2O2 treatment in CL1-5 by LC-MS/MS analysis. Besides, the apoptotic cells were decreased but no differences in CL1-0 while supplement reduced-GSH before H2O2 treatment. We therefore hypothesize that there are different processes on dealing with ROS scavenging post oxidative stress between CL1-0 and CL1-5. Taken together, using hydrogen peroxide for treating two lung cancer cell lines seem to have different DNA repair function to regulate cellular function. In the following experiments, the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase as well as glutathione peroxidase (GPx) post oxidative stress in CL1-0 and CL1-5 will be determined. Moreover, we will examine the level of GSH in different tumor cell lines to investigate whether GSH involved in tumor invasion ability. Citation Format: Feng- Chang Wu, Yu-Fen Lin, Liang-Chuan Lai, Eric Y Chuang, Mong-Hsun Tsai. To study DNA repair function of two closely related human lung adenocarcinoma cell lines, CL1-0 and CL1-5. [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 2914. doi:10.1158/1538-7445.AM2013-2914 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
SOME NOTES ON MILITARY ORTHOPAEDICS
Authors: R. W. Sutherland, J. M. Christie
Journal: BMJ (1920)

DiCALJOURNAt -I DCLJO NAconitaining it excised.If a strictutre is actually present or suture of the opening is likelyto narrow too muchl the lumen of jejunuim or colon, an appropriate resection will be necessary.In any case the establislhment of a temporary caecostomy is of the greatest value.Tlle sole purpose of suchi an opening is to prevent tlle accumulation offlatus in the colon above the suture line.By it the sutures are relieved from any strain and the patient is entirely-spared tlle discomfort and danger of post-operative distension.If thle pylorus is still obstructed and it is necessary to obliterate the anastomosis, a freslh gastro-enterostomy must be done or an extensive resection of the stoniiach, such as described by Clairmont.
STUDIES ON THE EFFECT OF THE CARRIER MOLECULE ON ANTIHAPTEN ANTIBODY SYNTHESIS
Authors: Gregory W. Siskind, William E. Paul, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1966)

1. Fluorescence quenching has been calibrated, by comparison with equilibrium dialysis, for measurement of antibody-hapten association constants with guinea pig antibody to the 2,4-dinitrophenyl (DNP) determinant. The maximum quenching with all sites occupied which gave best agreement with equilibrium dialysis was found to be 100%. 2. The carrier to which the DNP-hapten is coupled influences significantly the amount, class (γ1 or γ2), and affinity of the antibody of DNP specificity made by individual guinea pigs. 3. The affinities of γ1- and γ2-antibodies from individual guinea pigs are generally very similar. 4. Precipitin curves with γ1-antibodies show more marked inhibition of precipitation in antigen excess than do precipitin curves with the less charged γ2-antibodies, indicating the importance of nonspecific forces in the precipitation reactions.
Management of Precocious Puberty
Authors: Robert P. Kelch
Journal: New England Journal of Medicine (1985)

Precocious sexual development is a stressful condition for both the affected child and the family.1 Because of its relative rarity, numerous causes, and psychosocial complications, few other conditions pose as many diagnostic and therapeutic challenges. In this issue of the Journal, Holland et al. have described a novel approach to the management of an uncommon but severe form of precocious pseudopuberty in boys.2 An understanding of the neuroendocrine mechanisms responsible for normal sexual maturation, as well as the differential diagnosis of isosexual precocity, is necessary to place this new form of therapy in perspective.Maturation of the human reproductive . . .
<i>EGFR</i>Mutation Conferring Primary Resistance to Gefitinib in Non–Small-Cell Lung Cancer
Authors: Jin-Yuan Shih, Chien-Hung Gow, Pan-Chyr Yang
Journal: New England Journal of Medicine (2005)

To the Editor: Patients with lung cancer who respond to gefitinib have been reported to have somatic mutations consisting of deletions in exon 19 and the L858R mutation in exon 21 of the epidermal ...
Receptors, Neurotransmitters and Drug Responses
Authors: Solomon H. Snyder
Journal: New England Journal of Medicine (1979)

ABNORMALITIES in sensitivity to endogenous hormones and neurotransmitters as well as to exogenous drugs pervade clinical medicine. Idiosyncratic responses to medication are well known, but their causes are rarely ascertained. Although chronic decreases in sensitivity to drugs accompany classic forms of drug addiction, underlying mechanisms are unknown. Acute tolerance, also known as tachyphylaxis or desensitization, is fundamental to synaptic transmission and has many clinical manifestations, such as the decreased responsiveness of an asthmatic person to epinephrine after multiple administrations. Supersensitivity to endogenous or exogenous agents also has clinical relevance. Examples include the apparent supersensitivity to circulating catecholamines in hyperthyroidism and . . .
Intensifying the War Against Drunken Driving By Discouraging Alcohol Consumption in General
Authors: Charles Marwick
Journal: JAMA (1989)

THE CAMPAIGN against the drinking driver has taken a sharp new turn.  Until now most of the efforts to prevent alcohol-related motor vehicle accidents have involved testing for blood alcohol levels and imposing stiffer penalties for drinkers involved in accidents. But at the end of a three-day workshop on drunk driving convened by Surgeon General C. Everett Koop, MD, the participants presented Koop with a series of recommendations aimed at actively discouraging alcohol consumption in general.  Series of Recommendations  The group recommended the following:   Federal and state taxes on beer and wine be equalized by alcohol content to the same level as hard liquor and be indexed to the inflation rate.  Alcohol advertising and promotion of public events, where the majority of the audience is under the legal drinking age, be eliminated.  Advertising that portrays alcohol use also be banned.  The alcoholic beverage industry be forbidden to sponsor athletic events.
ACCURACY AND COST-EFFECTIVENESS OF DELAYED Tc-99m SESTAMIBI SPECT SCINTIGRAPHY IN DIAGNOSING PRIMARY HYPERPARATHYROIDISM.
Authors: A. C. Civelek, F. Alam, A. Mudun, A. Imperial, B. Chin, Z. Szabo, R. Udelsman
Journal: Clinical Nuclear Medicine (1997)

Civelek, A. C.; Alam, F.; Mudun, A.; Imperial, A.; Chin, B.; Szabo, Z.; Udelsman, R. Author Information
Oral Contraceptives and Myocardial Infarction
Authors: D. J. Radford, M. F. Oliver
Journal: BMJ (1973)

During 1965-9 22 women aged 41 years or less have been seen with myocardial infarction. Eleven had been taking oral contraceptives. This prevalence of oral contraception (50%) is appreciably greater than that estimated for women of the same age in the general population.Nine of these 11 women had an independent increased risk of developing ischaemic heart disease because of hyperlipidaemia, hypertension, or excessive cigarette smoking. Ten of the 11 not taking an oral contraceptive also had a readily identifiable predisposing factor. None of the 22 showed carbohydrate intolerance. The similarity of the two groups is the striking finding. Details of 15 women of comparable age seen during 1960-4 before oral contraceptives were widely used are also presented, and they had similar characteristics.Oral contraceptives do not appear on their own to increase the risk of developing myocardial infarction, but they may do so in women otherwise prone to ischaemic heart disease. Suggestions are made for the identification of these women.
Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients.
Authors: M Orozco-Levi, A Torres, M Ferrer, C Piera, M el-Ebiary, J P de la Bellacasa, R Rodriguez-Roisin
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The aim of this study was to evaluate the effect of two body positions (supine and semirecumbency) on the dynamics of gastroesophageal reflux (GER) in 15 patients requiring mechanical ventilation and having a nasogastric tube in place. Samples of gastric contents, pharyngeal and bronchial secretions, and blood were obtained at baseline and every hour during a period of 5 h after nasogastric tube isotopic instillation of 37 megabecquerels of Tc99m. Radioactivity counting (RAc) was performed using a gamma counter with correction for decay. Irrespective of the body position, all patients showed at 3, 4, and 5 h after the isotope instillation a significant increase in RAc of the oropharyngeal contents (p < 0.05, each), indicating GER. Although RAc values in the pharynx were higher in supine from 1 through 4 h (p < 0.05), at the end of the study (5 h) the values did not differ between each position. Likewise, the slopes of the regression lines of sequential oropharyngeal RAc values were not different between each position (0.39 +/- 0.09 versus 0.45 +/- 0.11, respectively). In contrast, RAc values in bronchial secretions were higher at 5 h in the supine position compared with baseline (p < 0.05) and to semirecumbency (p < 0.01). These results strongly support that GER in mechanically ventilated patients with a nasogastric tube is a feature occurring irrespective of body position. Semirecumbent position does not protect completely from GER and subsequently from oropharyngeal colonization from gastric origin.
Effect of acute ischemia, nitroglycerin and nitroprusside on regional myocardial thickening, stress and perfusion. Experimental echocardiographic studies.
Authors: R E Kerber, J B Martins, M L Marcus
Journal: Circulation (1979)

The purposes of this study were to demonstrate that echocardiography can be used to demonstrate the systolic wall thinning of acutely ischemic myocardium, and to compare the effects of nitroglycerin and nitroprusside on systolic thinning, wall stress and perfusion of ischemic myocardium. In 37 dogs, the ratio of end-systolic-to-end-diastolic posterior wall thickness fell from 1.30 +/- 0.02 to 0.88 +/- 0.01 ((p less than 0.001) after circumflex coronary occlusion; perfusion of the area supplied by the occluded artery fell from 98.2 +/- 7.5 ml/100 g/min to 36.5 +/- 2.9 ml/100 g/min (p less than 0.001). Nitroglycerin and nitroprusside were given to lower mean arterial pressure by 7% and 15%. Despite the reduction in coronary perfusion pressure, transmural perfusion, endocardial/epicardial perfusion ratio and systolic thinning remained constant. Both drugs reduced the ischemic "wall stress index" (ventricular pressure x ventricular diameter/wall thickness) by almost 50%. Thus, both nitroglycerin and nitroprusside were equally beneficial in this model of acute myocardial ischemia.
Management of Breast Cancer in Old Age
Authors: B. A. Stoll, T. H. Ackland
Journal: BMJ (1970)

In a retrospective survey of 301 women aged over 70 with breast cancer the factors affectingfive-year survival are evaluated. The local disease is more advanced when the patient presents with it in old age than in younger women, possibly associated with a lesser degree of awareness or a long history of the primary tumour. It is not associated with a different average rate of tumour growth in old age, as measured by scar recurrences after surgery. Radical surgery may be followed by a high five-year survival rate in patients carefully selected on medical grounds, but in this unselected series the five-year survival rate was practically the same whether the local disease was limited or extensive at presentation and whatever the treatment given. The probability of five-year survival in a woman over 70 with breast cancer will depend mainly on her general health.
The promotion of osteochondral repair by combined intra-articular injection of parathyroid hormone-related protein and implantation of a bi-layer collagen-silk scaffold
Authors: Wei Zhang, Jialin Chen, Jiadong Tao, Changchang Hu, Longkun Chen, Hongshi Zhao, Guowei Xu, Boon C. Heng, Hong Wei Ouyang
Journal: Biomaterials (2013)
Medical Diagnosis and Treatment of Alcoholism
Authors: Barbara G. Orrok
Journal: JAMA (1993)

This is another in a series of fine textbooks by this team about alcohol and its effects. Editors Mendelson and Mello have assembled a group of highly distinguished authors who synthesize extensive information and refrain from using their chapters as a showcase for their work. The slender volume contains a comprehensive selection of topics. Diagnosis, medical pathology, and treatment are all covered. Chapters are devoted to special populations, including geriatric, fetal, and cultural minorities in the United States. Of special note is the attention to compiling and addressing information pertinent to women. Lex describes the nature of medical, social, and psychological alcohol-related problems in women as well as women's response to treatment. Mello, Mendelson, and Teoh review essentially everything known about the various neuroendocrine effects of alcohol in women of reproductive age. Gavaler reviews work done in understanding the effects of alcohol on estrogens in postmenopausal women. A number of
Poor outcome after reintroduction of imatinib in patients with chronic myeloid leukemia who interrupt therapy on account of pregnancy without having achieved an optimal response
Authors: Aya Kuwabara, Anna Babb, Amr Ibrahim, Dragana Milojkovic, Jane Apperley, Marco Bua, Alistair Reid, Letizia Foroni, Katayoun Rezvani, John Goldman, David Marin
Journal: Blood (2010)
A Critical Role for STAT3 Transcription Factor Signaling in the Development and Maintenance of Human T Cell Memory
Authors: Andrea M. Siegel, Jennifer Heimall, Alexandra F. Freeman, Amy P. Hsu, Erica Brittain, Jason M. Brenchley, Daniel C. Douek, Gary H. Fahle, Jeffrey I. Cohen, Steven M. Holland, Joshua D. Milner
Journal: Immunity (2011)
670 Effect of portal hemodynamics on liver regeneration, studied in a novel porthhepatic shunt rat model
Authors: S MARUBASHI, M SAKON, H NAGANO, A MIYAMOTO, K DONO, S NAKAMORI, K UMESHITA, M MONDEN
Journal: Hepatology (2003)

Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure–activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coupled to bovine serum albumin (BSA), induces anti-mitochondrial antibodies (AMAs) and cholangitis. Based upon these data, we have focused on covalent modifications of the lipoic acid disulfide ring and subsequent analysis of such xenobiotics coupled to a 15mer of PDC-E2 for immunoreactivity against a broad panel of sera from patients with PBC and controls. Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S–S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. This observation is particularly significant in light of the function of the lipoyl moiety in electron transport of which the catalytic disulfide constantly opens and closes and, thus, raises the intriguing thesis that common electrophilic agents, i.e. acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs), may lead to xenobiotic modification in genetically susceptible individuals that results in the generation of AMAs and ultimately clinical PBC.