tbuckley/cabot-search huggingface dataset:
Gonadotropin-Releasing Hormone Agonists and Fracture Risk: A Claims-Based Cohort Study of Men With Nonmetastatic Prostate Cancer
Authors: Matthew R. Smith, Won Chan Lee, Jane Brandman, Qin Wang, Marc Botteman, Chris L. Pashos
Journal: Journal of Clinical Oncology (2005)

Purpose Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density, a surrogate for fracture risk, in men with prostate cancer. We conducted a claims-based cohort study to characterize the relationship between GnRH agonists and risk for clinical fractures in men with nonmetastatic prostate cancer. Patients and Methods Using medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group of men with nonmetastatic prostate cancer who initiated GnRH agonist treatment from 1992 to 1994 (n = 3,887). A comparison group of men with nonmetastatic prostate cancer who did not receive GnRH agonist treatment during the study period (n = 7,774) was matched for age, race, geographic location, and comorbidity. Clinical fractures were identified using inpatient, outpatient, and physician claims during 7 years of follow-up. Results In men with nonmetastatic prostate cancer, GnRH agonists significantly increased fracture risk. The rate of any clinical fracture was 7.88 per 100 person-years at risk in men receiving a GnRH agonist compared with 6.51 per 100 person-years in matched controls (relative risk, 1.21; 95% CI, 1.14 to 1.29; P &lt; .001). Rates of vertebral fractures (relative risk, 1.45; 95% CI, 1.19 to 1.75; P &lt; .001) and hip/femur fractures (relative risk, 1.30; 95% CI, 1.10 to 1.53; P = .002) were also significantly higher in men who received a GnRH agonist. GnRH agonist treatment independently predicted fracture risk in multivariate analyses. Longer duration of treatment conferred greater fracture risk. Conclusion GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer.
Initial Management of Epilepsy
Authors: Jacqueline A. French, Timothy A. Pedley
Journal: New England Journal of Medicine (2008)

A 29-year-old woman reports that the previous evening, her husband (who was in the next room) heard unusual sounds and found her lying on the bed looking dazed. She was confused for a few minutes but quickly returned to normal. She recalls an unwitnessed event about 1 month previously when she awoke feeling mildly confused and had sore muscles. How should she be evaluated and treated?
Absorption of glycine and L-alanine by the human jejunum.
Authors: B Fleshler, J H Butt, J D Wismar
Journal: Journal of Clinical Investigation (1966)

Most, if not all, ingested protein is degraded into amino acids, which are then absorbed.Ab- sorption of amino acids has been studied in intact animals, everted gut sacs, and in other preparations of intestine.These studies have been re- viewed recently (1, 2).Comparatively little is known, however, about amino acid absorption in the human.Kuroda and Gimbel (3) showed that when racemic amino acids were placed in the iso- lated ileal loop of a patient operated on for ul- cerative colitis, the L-isomer disappeared faster than the D-isomer.Cummins (4) reported a di- rectly proportional increase in the amount of DLmethionine that disappeared from a length of gut when the concentration of the amino acid was doubled.The kinetics of absorption of L-methio- nine at various sites in the human small intestine were determined by Schedl and Clifton (5).The uptake of certain amino acids by human intesti- nal biopsy specimens is dependent, at least in part, on active transport (6, 7).This report presents results of studies on ab- sortion of glycine and L-alanine in human sub- jects.These amino acids were chosen for study because considerable information is available about their absorption by in vitro preparations.Glycine and L-alanine in man appear to be absorbed by active transport processes and to share a common absorptive pathway for which L-alanine has greater affinity.These findings agree with the results of studies in tissue preparations.
Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases
Authors: Xin He, Zhigang Chen, Yangyan Jiang, Xi Qiu, Xiaoying Zhao
Journal: Journal of Hematology & Oncology (2013)

Abstract The human c-mpl gene ( MPL ) plays an important role in the development of megakaryocytes and platelets as well as the self-renewal of haematopoietic stem cells. However, numerous MPL mutations have been identified in haematopoietic diseases. These mutations alter the normal regulatory mechanisms and lead to autonomous activation or signalling deficiencies. In this review, we summarise 59 different MPL mutations and classify these mutations into four different groups according to the associated diseases and mutation rates. Using this classification, we clearly distinguish four diverse types of MPL mutations and obtain a deep understand of their clinical significance. This will prove to be useful for both disease diagnosis and the design of individual therapy regimens based on the type of MPL mutations.
Validity, reliability and responsiveness of patient-reported outcome questionnaires when assessing hip and groin disability: a systematic review
Authors: K Thorborg, EM Roos, EM Bartels, J Petersen, P Hölmich
Journal: British Journal of Sports Medicine (2009)

Background Novel treatment interventions are advancing rapidly in the management of hip and groin disability in the physically active young to middle-aged population. Objective To recommend the most suitable patient-reported outcome (PRO) questionnaires for the assessment of hip and groin disability based on a systematic review of evidence of validity, reliability and responsiveness of these instruments. Methods MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO, SportsDiscus and Web of Science were all searched up to January 2009. Two reviewers independently rated measurement properties of the PRO questionnaires in the included studies, according to a standardised criteria list. Results The computerised search identified 2737 publications. Forty-one publications investigating measurement properties of PRO questionnaires assessing hip or groin disability were included in the study. Twelve different questionnaires designed for patients with hip disability and one questionnaire for patients with groin disability were identified. Hip dysfunction and Osteoarthritis Outcome Score (HOOS) contains adequate measurement qualities to evaluate patients with hip osteoarthritis (OA) or total hip replacement (THR). Hip Outcome Score (HOS) is the best available questionnaire for evaluating hip arthroscopy, but the Inguinal Pain Questionnaire, the only identified questionnaire evaluating groin disability, does not contain adequate measurement qualities. Conclusions HOOS is recommended for evaluating patients with hip OA undergoing non-surgical treatment and surgical interventions such as THR. HOS is recommended for evaluating patients undergoing hip arthroscopy. Current and new PRO questionnaires should also be evaluated in younger patients (age &lt;50) with hip and/or groin disability, including surgical and non-surgical patients.
Method for Intravenous Administration of Heparin in Myocardial Infarction
Authors: R. McG. Harden
Journal: BMJ (1963)

Three cases of portal phlebothrombosis during the puerperium, with infarction of bowel, are described, together with a review of the literature.Possible aetiological factors are discussed.The conjunc- tion of the thrombosis with changes in the blood, particularly the platelets, is stressed.A plea is made that similar cases be reported.Our thanks are due to Mr. R. W. Knowlton, under whose care Cases 1 and 2 were admitted to hospital; to Dr.
SPIRIT AND BIPP TREATMENT
Authors: N. L. M. Reader
Journal: BMJ (1928)

SPIRIT AND BIPP TRE:ATAMENT. TEarCRIT1311the levatores aini muscles, in order to bring these muiscles and tho posterior vaginal wall inito close apposition (Flig.3).The skin edges aro next uniited with.initer- rupted catgut sutuiues and tho silkworm-gut sutures tied through small pieces of india-rubber tubing, tlhus completing tho oper;ation (Fig. 4).The last or most posterior silkwormi-gut suture is passed so as to prevent the anal or ifice falling backwards,-which is not inifrequient after operationls for comp)lete rupture of the perineumii.Catgut may also be employed for this suture.
Preclinical and Clinical Development of Cyclin-Dependent Kinase Modulators
Authors: A M Senderowicz, E A Sausville
Journal: JNCI Journal of the National Cancer Institute (2000)

In the last decade, the discovery and cloning of the cyclin-dependent kinases (cdks), key regulators of cell cycle progression, have led to the identification of novel modulators of cdk activity. Initial experimental results demonstrated that these cdk modulators are able to block cell cycle progression, induce apoptotic cell death, promote differentiation, inhibit angiogenesis, and modulate transcription. Alteration of cdk activity may occur indirectly by affecting upstream pathways that regulate cdk activity or directly by targeting the cdk holoenzyme. Two direct cdk modulators, flavopiridol and UCN-01, are showing promising results in early clinical trials, in which the drugs reach plasma concentrations that can alter cdk activity in vitro. Although modulation of cdk activity is a well-grounded concept and new cdk modulators are being assessed for clinical testing, important scientific questions remain to be addressed. These questions include whether one or more cdks should be inhibited, how cdk inhibitors should be combined with other chemotherapy agents, and which cdk substrates should be used to assess the biologic effects of these drugs in patients. Thus, modulation of cdk activity is an attractive target for cancer chemotherapy, and several agents that modulate cdk activity are in or are approaching entry into clinical trials.
Blood pressure response to central and/or peripheral inhibition of phenylethanolamine N-methyltransferase in normotensive and hypertensive rats.
Authors: J Black, B Waeber, M R Bresnahan, I Gavras, H Gavras
Journal: Circulation Research (1981)

We studied the effects on blood pressure and heart rate of two different phenylethanolamine N-methyltransferase (PNMT) inhibitors in normotensive, in two-kidney renal hypertensive, and in deoxycorticosterone-salt (DOC-salt) hypertensive rats. One compound (SK&amp;F 64139) blocks the conversion of norepinephrine to epinephrine in both the central and the peripheral nervous system, whereas the other (SK&amp;F 29661) does not cross the blood-brain barrier and therefore is active mostly in the adrenal glands. In the rats given SK&amp;F 29661, practically no acute blood pressure changes were in the adrenal glands. In the rats given SK&amp;F 64139 induced only a minor blood pressure and heart rate response in normotensive and two-kidney renal hypertensive rats. However, in DOC-salt hypertensive rats, it reduced arterial pressure to approximately normal levels and concomitantly slowed pulse rate. There was a close correlation between the magnitude of the blood pressure response observed in all SK&amp;F 64139-treated animals and the control plasma norepinephrine (4 = -0.795, P less than 0.001) and epinephrine (r = -0.789, P less than 0.001) levels. These results suggest an important role for central epinephrine in regulating the peripheral sympathoadrenomedullary and the baroreceptor reflex activity, particularly when the maintenance of the high blood pressure is not renin-dependent.
The Panton–Valentine leukocidin vaccine protects mice against lung and skin infections caused by Staphylococcus aureus USA300
Authors: E.L. Brown, O. Dumitrescu, D. Thomas, C. Badiou, E.M. Koers, P. Choudhury, V. Vazquez, J. Etienne, G. Lina, F. Vandenesch, M.G. Bowden
Journal: Clinical Microbiology and Infection (2008)
Disparities in Gastric Cancer Chemotherapy Between the East and West
Authors: Atsushi Ohtsu, Shigeaki Yoshida, Nagahiro Saijo
Journal: Journal of Clinical Oncology (2006)

There are still remarkable disparities in the treatment of gastric cancer between the East and West. Treatment outcomes for this disease have improved in Japan due to early detection and surgical resection with systematic node dissections, such as D2, whereas gastric cancer remains a virulent disease in Western countries. Differences in the types of surgery and their outcomes affect how adjuvant trials are conducted and interpreted. Recent Western randomized trials demonstrated the significant survival benefit of adjuvant chemoradiotherapy or intensive combination chemotherapy. However, baseline surgical quality and outcomes were quite different from those in Japan, and Japanese surgical/medical oncologists have not accepted the Western results. Several disparities are also evident in the results of chemotherapy trials for advanced gastric cancer. Although similar results were obtained with randomized studies using older regimens, the interpretation of the results differed between Japan and other countries. A combination of cisplatin and fluorouracil was used as the reference arm in ongoing randomized trials in most countries, whereas single-agent fluorouracil or S-1 alone was used in Japanese trials. Two triplet regimens have already demonstrated significant prolongation of survival in Western studies. However, these benefits seem to be marginal and these regimens may be replaced by newer regimens, which will soon be available in Europe and Asia, where a total of 2,600 patients have been accrued. Although these disparities between regions must be overcome, it is time for both Eastern and Western investigators to pursue further benefits by incorporating new agents into treatment regimens.
Genome-wide promoter extraction and analysis in human, mouse, and rat.
Authors: Zhenyu Xuan, Fang Zhao, Jinhua Wang, Gengxin Chen, Michael Q Zhang
Journal: Genome biology (2005)

Abstract Large-scale and high-throughput genomics research needs reliable and comprehensive genome-wide promoter annotation resources. We have conducted a systematic investigation on how to improve mammalian promoter prediction by incorporating both transcript and conservation information. This enabled us to build a better multispecies promoter annotation pipeline and hence to create CSHLmpd (Cold Spring Harbor Laboratory Mammalian Promoter Database) for the biomedical research community, which can act as a starting reference system for more refined functional annotations.
The Butler Did It
Authors: M. THERESE SOUTHGATE
Journal: JAMA (1976)

Whether it be an intellectual Dorothy Sayers, a clever Agatha Christie, the latest psychological Simenon—or for that matter, the article on page 1849 of this issue ofThe Journal—the ele ments of a good whodunit are much the same. For, like the best fictional mystery stories, the account of the epidemiological investigation by Rosenberg, Hazlet, and Schaefer could not have been better plotted. The place is the Mississippi River, along the bluffs below Dubuque; the time, summer 1974, just before school begins. The characters are some 45 youngsters, aged 9 years and thereabouts who have been attacked by a member of the<i>Shigella</i>family: the villainous<i>sonnei</i>. The villain in turn is being stalked by detectives, in this case, the authors themselves, supported by a large force of state, local, and national health authorities. But the case is baffling. The villain has apparently changed his MO; never before has
Glioblastoma Stem Cells Are Regulated by Interleukin-8 Signaling in a Tumoral Perivascular Niche
Authors: David W. Infanger, YouJin Cho, Brina S. Lopez, Sunish Mohanan, S. Chris Liu, Demirkan Gursel, John A. Boockvar, Claudia Fischbach
Journal: Cancer Research (2013)

Abstract Glioblastoma multiforme contains a subpopulation of cancer stem–like cells (CSC) believed to underlie tumorigenesis and therapeutic resistance. Recent studies have localized CSCs in this disease adjacent to endothelial cells (EC) in what has been termed a perivascular niche, spurring investigation into the role of EC–CSC interactions in glioblastoma multiforme pathobiology. However, these studies have been limited by a lack of in vitro models of three-dimensional disease that can recapitulate the relevant conditions of the niche. In this study, we engineered a scaffold-based culture system enabling brain endothelial cells to form vascular networks. Using this system, we showed that vascular assembly induces CSC maintenance and growth in vitro and accelerates tumor growth in vivo through paracrine interleukin (IL)-8 signaling. Relative to conventional monolayers, endothelial cells cultured in this three-dimensional system not only secreted enhanced levels of IL-8 but also induced CSCs to upregulate the IL-8 cognate receptors CXCR1 and CXCR2, which collectively enhanced CSC migration, growth, and stemness properties. CXCR2 silencing in CSCs abolished the tumor-promoting effects of endothelial cells in vivo, confirming a critical role for this signaling pathway in GMB pathogenesis. Together, our results reveal synergistic interactions between endothelial cells and CSCs that promote the malignant properties of CSCs in an IL-8–dependent manner. Furthermore, our findings underscore the relevance of tissue-engineered cell culture platforms to fully analyze signaling mechanisms in the tumor microenvironment. Cancer Res; 73(23); 7079–89. ©2013 AACR.
Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema
Authors: S.O. Shaheen, R.B. Newson, A.J. Henderson, P.M. Emmett, A. Sherriff, M. Cooke
Journal: European Respiratory Journal (2004)

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30–42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0–6 months and 30–42 months, respectively (n=2,044), and with eczema at 18–30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.
Antibiotic prescribing in the community
Authors: M. THOMAS;
Journal: Thorax (2000)

Opportunist" mycobacterial infectionsWe were greatly impressed by the Joint Tuberculosis Committee guidelines on the management of opportunist mycobacterial infections. 1 We do, however, wonder why the word "opportunist" has been used to describe the mycobacteria, other than the M tuberculosis complex, that cause human disease.All mycobacteria causing disease, even the M tuberculosis complex, are opportunists.Thus, the latter are often spoken of as causing opportunist disease in HIV positive persons.Since the causative role of these other mycobacteria in human disease was established in the middle of the 20th century, a wide range of collective nouns has been applied to them-atypical, anonymous, MOTT (mycobacteria other than tuberculosis), nontuberculous, and tuberculoid-as well as opportunist.The distinguishing feature of almost all mycobacteria other than members of the M tuberculosis complex is that they live freely in the environment.For this reason the expression "environmental mycobacteria" has been in widespread use in recent years.May we suggest that, for uniformity, this expression should be universally adopted.
Sweating and its Disorders
Authors: P M Quinton
Journal: Annual Review of Medicine (1983)

Eccrine sweat is produced by millions of miniscule glands buried in the skin. Eccrine sweating from the general body surface is an extremely important function in human thermoregulation; disturbances either in the control of sweating activity or in the glands themselves can result in problems ranging from minor social embarrassment to fatal hyperpyrexia. A general review of the function and control of normal sweating precedes an overview of sweating abnormalities.
Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma
Authors: Yilei Mao, Huayu Yang, Haifeng Xu, Xin Lu, Xinting Sang, Shunda Du, Haitao Zhao, Wang Chen, Yiyao Xu, Tianyi Chi, Zhiying Yang, Jianqiang Cai, Hui Li, Jianguo Chen, Shouxian Zhong, Smruti R Mohanti, Reynold Lopez-Soler, J Michael Millis, Jiefu Huang, Hongbing Zhang
Journal: Gut (2010)

<h3>Background and aims</h3> Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC. <h3>Methods</h3> Serum GP73 and alpha-fetoprotein (AFP) were compared in a total of 4217 human subjects in this multicentre study, including 1690 healthy adults, 337 hepatitis B virus (HBV) carriers, 512 patients with cirrhosis, 789 patients with HCC, 61 patients with other malignant liver lesions, 206 patients with benign liver lesions and 622 patients with 14 different kinds of non-liver cancers. The main outcome measures were the specificity and sensitivity of GP73 in patients at risk for the development of HCC. <h3>Results</h3> Using 8.5 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 74.6% (95% CI 71.5% to 77.6%) and 97.4% (95% CI 96.8 to 98.3%), compared with 58.2% (95% CI 55.2% to 62.1%) and 85.3% (95% CI 83.4% to 88.1%) for AFP (p&lt;0.001) using 35 ng/ml as a cut-off value. The GP73 level was significantly increased in patients with HCC compared with healthy controls (14.7 vs 1.2, p&lt;0.001). Although GP73 levels in HBV carriers (2.9) and patients with cirrhosis (4.7) were somewhat elevated, they were much lower than that in patients with HCC (p&lt;0.001). GP73 decreased following surgical resection of HCC lesions and increased with tumour recurrence. Fourteen types of non-liver cancers were analysed; all the benign and other malignant liver lesions had moderate elevations of GP73, albeit at a much lower level than in HCC. <h3>Conclusions</h3> GP73 is an accurate serum marker for the detection of HCC and its recurrence after surgery, with higher sensitivity and specificity than AFP. Clinical implementation of serum GP73 measurement as a standard test for HCC is recommended.