tbuckley/cabot-search huggingface dataset:
Abstract LB-277: Irregular menstruation predicts increased risk of subsequent ovarian cancer death in a prospective cohort, The Child Health and Development Studies
Authors: Barbara A. Cohn, Piera M. Cirillo, Erica T. Wang, Marcelle I. Cedars
Journal: Cancer Research (2014)

Abstract Background. Early detection of ovarian cancer has proved elusive, resulting in poor survival. This is the first prospective study to link a common reproductive condition to risk. Polycystic ovarian syndrome (PCOS) is an endocrine disorder, characterized by irregular menstrual cycles with long-term health consequences. Although some women with PCOS are infertile, the majority achieve pregnancy. It has been suggested that women with less frequent ovulation are protected, however, previous reports are inconsistent. Here we examine whether irregular cycling is associated with subsequent ovarian cancer death in a large prospective pregnancy cohort, The Child Health and Development Studies. Methods. Subjects were 14,403 pregnant women recruited from the Kaiser Permanente Health Plan in 1959-1967 and followed for over 50 years. Menstrual irregularity, cycles &amp;gt;35 days or anovulation, was a proxy for PCOS, identified from medical record and self-report, at a median age of 26 years in 13% of women. Linkage to California Vital Statistics and National Death Index records identified 64 ovarian cancer deaths diagnosed at a median age of 69 years. Results. Contrary to expectations, women with irregular cycles had a two-fold greater risk of ovarian cancer (Hazard Ratio=2.4; 95% Confidence Interval=1.3,4.5), independent of age, race, parity, and weight. This association was specific to cancer of the ovary - no association was observed for breast or uterine cancer - and it increased over the follow-up period (p=0.08 for time-dependence). Conclusions. This is the first large prospective study of irregular cycles as an early marker of ovarian cancer. If confirmed, women with irregular cycles could be targeted for screening. This finding offers a strategy to search for antecedent ovarian cancer biomarkers, creating the opportunity for new early detection strategies. Citation Format: Barbara A. Cohn, Piera M. Cirillo, Erica T. Wang, Marcelle I. Cedars. Irregular menstruation predicts increased risk of subsequent ovarian cancer death in a prospective cohort, The Child Health and Development Studies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-277. doi:10.1158/1538-7445.AM2014-LB-277
Assessment of fibrin degradation products during fibrinolytic therapy for acute myocardial infarction.
Authors: C W Francis, D G Connaghan, V J Marder
Journal: Circulation (1986)

In a group of 39 patients who received fibrinolytic therapy for acute myocardial infarction, serum crosslinked fibrin degradation products (XLDP) were quantitated by an enzyme-linked immunosorbent assay (ELISA) using an antibody reactive with a site near the gamma gamma crosslink of fibrin, and characterized by a gel electrophoretic method to distinguish fibrinogen degradation products (FDP) from XLDP. After coronary artery reperfusion, 63 of 81 (69%) serum samples showed XLDP by gel analysis, whereas the incidence of positive samples before reperfusion, 53 of 144 (37%), was significantly less (p less than .0001). The first appearance of serum XLDP by gel analysis was most often in the 15 min interval immediately before or after angiographic documentation of reperfusion, and the elapsed treatment time required to produce a positive test was shorter with more intensive treatment regimens. However, the appearance of serum XLDP was not a specific indicator of reperfusion in individual patients, since one or more serum samples was positive in five of eight patients who did not show reperfusion as well as in 27 of 29 patients who did show reperfusion. Furthermore, the concentration of serum XLDP as measured by ELISA showed no significant difference in samples from patients who did or did not have reperfusion or between samples taken before or after reperfusion. There was a close temporal correlation between the first appearance of serum XLDP (gel analysis) and the initial decrease in plasma fibrinogen (systemic lytic state), and the degree of elevation of serum XLDP (ELISA) was also correlated with the intensity of the systemic lytic state. In addition, electrophoretic analysis of pretreatment plasma samples demonstrated crosslinked fibrin polymers that disappeared during fibrinolytic therapy coincident with the appearance of serum XLDP and in parallel with fibrinogen conversion to degradation products (fragments X, Y, and D). Two patients without a lytic state showed no change in plasma fibrin polymers during therapy, and XLDP were not present in serum despite coronary reperfusion in one patient. Thus the results indicate that XLDP appearing in the blood during fibrinolytic therapy for acute myocardial infarction are not predictive of successful fibrinolytic therapy, but rather may reflect degradation of circulating fibrin polymers associated with the fibrinogenolysis of the systemic lytic state.
Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial
Authors: Q. Zhou, Y. Cheng, J.-J. Yang, M.-F. Zhao, L. Zhang, X.-C. Zhang, Z.-H. Chen, H.-H. Yan, Y. Song, J.-H. Chen, W.-N. Feng, C.-R. Xu, Z. Wang, H.-J. Chen, W.-Z. Zhong, Y.-P. Liu, Y.-L. Wu
Journal: Annals of Oncology (2014)
Growth Hormone
Authors: M. S. Raben
Journal: New England Journal of Medicine (1962)

HUMAN growth hormone is the most recent addition to the list of clinically useful hormones, though it will be some time before its range of usefulness is defined and undoubtedly a still longer time before an adequate source of clinically active material is devised. The delay in its clinical application is largely attributable to the tardy recognition of the evolutionary changes both in the chemical structure of growth hormone and in the tissue receptors for the growth-promoting agent.1 2 3 4 The growth hormone synthesized by human pituitary glands is a different substance from that made by beef, and both differ from that . . .
Cytomegalovirus Retinitis in Immunosuppressed Hosts
Authors: RICHARD B. POLLARD
Journal: Annals of Internal Medicine (1980)

Cytomegalovirus (CMV) retinitis presents with typical ophthalmologic appearance in patients with underlying immunosuppressive conditions. Fourteen patients with this disorder were diagnosed by culture of cytomegalovirus from urine or throat specimens, elevated complement fixation titers to cytomegalovirus, and characteristic funduscopic appearance. Ten of 11 had decreased CMV-specific cell-mediated immune responses. Three of seven who received no specific therapy improved after decreasing dosages of immunosuppressive drugs. Seven patients with progressive disease despite minimal immunosuppressive therapy were treated with adenine arabinoside at doses from 1 to 20 mg/kg of body weight per day. Daily dosages of 20 mg/kg · d in five patients were associated with decreased inflammatory activity and improvement of retinal lesions and quantitative decreases in urinary virus excretion. Adenine arabinoside administration was associated with significant gastrointestinal, hematologic, and neurologic side effects. Adenine arabinoside may have some beneficial effect on selected patients with progressive CMV retinitis.
A NEW METHOD OF DEALING WITH BOWEL PERFORATIONS COMMUNICATING WITH PELVIC ABSCESSES.
Authors: THOMAS W. HUNTINGTON
Journal: JAMA (1902)

The problem of dealing with old bowel perforations in the presence of purulent collections in the pelvic area is fraught with many perplexities. I refer particularly to the fistulous communications between the bowel and tubal or tubo-ovarian abscess sacs. Such lesions present a twofold aspect: 1, as regards the immediate risk to the patient's life from general septic peritonitis; 2, as to the likelihood of establishing a permanent fecal fistula with its external outlet through Douglas' pouch or through the abdominal wound. In this class of cases the visceral peritoneum, for several centimeters on either side of the perforation, has usually become thickened by a deposit of plastic material and has virtually lost its identity as a serous membrane. Immediate closure of a bowel perforation with such an environment by any of the suture methods, has in the majority of cases proven disappointing. The intestinal coats are so altered as
618. A Novel Gene Therapy Strategy for Vascular Ehlers-Danlos Syndrome by the Combination with RNAi Mediated Inhibition of a Mutant Allele and Transcriptional Activation of a Normal Allele
Authors: Atsushi Watanabe, Takahito Wada, Kumiko Tei, Ryuichiro Hata, Yoshimitsu Fukushima, Takashi Shimada
Journal: Molecular Therapy (2005)

Vascular Ehlers-Danlos syndrome (vascular EDS, also known as EDSIV), is a life-threatening dominantly inherited disorder caused by mutations in the gene for type III procollagen (COL3A1). Affected individuals are at risk for arterial, bowel and uterine rupture. There is no effective treatment to prevent the symptom associated with vascular EDS. Although gene therapy is an important option for treatment of genetic disorders, addition of the defective gene is not applicable for dominant diseases such as vascular EDS. To establish a therapeutic strategy for dominant inherited diseases, we examined the feasibility of two approaches. In the first experiment, we tested RNAi mediated inhibition of the mutant allele. Approximately one third of the known mutations of vascular EDS occur at 5' donor splice sites. Therefore, if aberrantly spliced mRNA could be selectively destroyed by RNAi, it might be possible to reduce the mutant COL3A1 level and increase the relative concentration of normal triple helix. We synthesized several small interfering RNA (siRNA) molecules targeting the extra intron sequence specific for mutant mRNA and introduced into patient's fibroblasts. Quantitative measurement of COL3A1 mRNA showed that mutant mRNA levels could be selectively decreased up to 80 % by transient transfection of one of the siRNA molecules. In the second experiment, we attempted to increase the concentration of normal COL3A1 mRNA, since half-dose of COL3A1 may not be sufficient to prevent vascular EDS symptoms. Lysyl oxidase(LOX)is a bifunctional protein carrying activities of both an extracellular enzyme that controls the maturation of collagen and elastin and an intracellular tranascriptional activator for the human collagen III promoter. When patient's cells were transfected with mutant specific siRNA and LOX expression vector, specific inhibition of the mutant allele and enhancement of the normal allele were observed. The concentration of normal COL3A1 mRNA was increased up to nearly normal level in control cells. These results strongly suggest that the combination of RNAi mediated mutant allele specific gene silencing and transcriptional activation of a normal allele is a useful strategy for phenotypic correction of dominant inherited diseases.
A METHOD FOR THE RAPID PREPARATION OF FRESH TISSUES FOR THE MICROSCOPE.
Authors: LOUIS B. WILSON
Journal: JAMA (1905)

While engaged in general pathologic work I shared the common distrust of frozen sections of fresh tissues for microscopic diagnosis. On taking charge recently of the laboratories of the Drs. Mayo, surgeons, I carefully tested the various methods hitherto published and found them either too slow for results while the patient waits under the anesthetic or else giving poorly differentiated cell detail. After considerable experimentation the following technic was discovered, and for the last six months it has given uniformly excellent preparations: Bits of fresh tissue not more than 2×10×10 mm. are frozen in dextrin solution and cut in sections of from 10 to 15 microns thick. The sections are removed from the knife with the tip of the finger and allowed to thaw thereon. The sections are unrolled with camel's-hair brushes in 1 per cent. NaCl solution. The sections are stained from 10 to 20 seconds in neutral Unna's
The ionic control of 1,25-dihydroxyvitamin D3 synthesis in isolated chick renal mitochondria. The role of calcium as influenced by inorganic phosphate and hydrogen-ion.
Authors: D D Bikle, E W Murphy, H Rasmussen
Journal: Journal of Clinical Investigation (1975)

Isolated kidney mitochondria prepared from Vitamin D-deficient chicks catalyze the conversion of 25-hydroxyvitamin D3 to 1,25 dihydroxyvitamin D3. It wasfound that changes in the concentrations of Ca-2plus, HPO4-2minus, and Hplus altered synthesis in an interrelated fashion. Increasing the Ca-2plus concentration from 10-6 to 10-5 M caused a four- to fivefold increase in 1 alpha-hydroxylase activity when the medium pH was between 6.5 and 7.0. increasing the [Ca2+] to 10-4 M caused to furhter stimulation. At higher pH values, Ca-2plus had little effect upon 1 alpha-hydroxylase activity. In the absence of calcium [Ca2+] less than or equal to 10-7 M), a change in pH from 6.5 to 7.1 had no effect upon 1 alpha-hydroxylase activity in the presence of 10-5 M calcium, increasing the medium pH had a biphasic effect. An increase in pH from 6.5 to 6.9 caused a 1.5-fold increase in 1 alpha-hydroxylase activity, but a further increase of the pH to 7.1 caused a profound decrease in rate of hydroxylation to approximately 20% of the peak value. Neither 10-5 M LaC13 nor 10 mug/ml of oligomycin altered the effects of Ca2+ upon hydroxylate activity. However, the effect of calcium was blocked by 2.5 times 10-5 M ruthenium red, 0.83 mug/ml of antimycin A, and 500 muM dinitrophenol. The clcium ionophore, A23187, decreased but did not prevent the stimulatory effect of calcium. These data are consistent with the concept that the [Ca2+ in the mitochondrial matrix space is of importance in regulating the 1 alpha-hydroxylase. Phosphate exerted a biphasic effect on 1,25(OH)2D3 production with maximal stimulation (approximately twofold) at 1-3 mM. Calcium enhanced the stimulation by phosphate at all concentrations studied. The presence of potassium modified the interrelated effects of calcium and phosphate in two ways: 10-3 M calcium blocked the stimulation by phosphate; and in the presence of phosphate, 10-3 M calcium resulted in less 1,25(OH)2D3 production by production by isolated mitochondria are qualitatively similar to the effects of these ions on 1,25(OH)2D3 production yb isolated renal tubules.
Assessment of regional and global left ventricular function by rest 201‐TI Gated SPECT in patients with coronary artery disease and left ventricular dysfunction
Authors: M. Ravani, P. Bertolaccini, R. Bonini, C. Palmieri, G. Manfredini, M. Terrazzi, A. Rizza, S. Maffei, A. Maneschi, A. Biagini
Journal: European Journal of Heart Failure (2000)
Oxidation of CaMKII determines the cardiotoxic effects of aldosterone
Authors: B Julie He, Mei-ling A Joiner, Madhu V Singh, Elizabeth D Luczak, Paari Dominic Swaminathan, Olha M Koval, William Kutschke, Chantal Allamargot, Jinying Yang, Xiaoqun Guan, Kathy Zimmerman, Isabella M Grumbach, Robert M Weiss, Douglas R Spitz, Curt D Sigmund, W Matthijs Blankesteijn, Stephane Heymans, Peter J Mohler, Mark E Anderson
Journal: Nature Medicine (2011)
Prenatal Exposure to Polychlorinated Biphenyls and Postnatal Growth: A Structural Analysis
Authors: Matthew R. Lamb, Sylvia Taylor, Xinhua Liu, Mary S. Wolff, Luisa Borrell, Thomas D. Matte, Ezra S. Susser, Pam Factor-Litvak
Journal: Environmental Health Perspectives (2005)

Normal endocrine function in utero and early in childhood influences later height and weight attainment. Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with suspected endocrine-disrupting properties. PCBs may mimic or inhibit hormone and endocrine processes based in part on their structural configuration, with non-ortho-substituted PCBs having a coplanar orientation and ortho-substituted PCBs becoming increasingly noncoplanar. Coplanar and noncoplanar PCBs have known differences in biologic effect. Animal studies link prenatal PCB exposure to adverse birth and early-life growth outcomes, but epidemiologic studies are conflicting. We examined whether prenatal exposure to PCBs, categorized by their degree of ortho-substitution, affected childhood height and weight attainment in 150 children (109 boys and 41 girls) with African-American mothers born at the Columbia-Presbyterian Hospital from 1959 through 1962. Stratifying by sex, we used regression models for repeated measures to investigate associations between maternal levels of PCBs and height and weight through 17 years of age. Maternal levels of ortho-substituted PCBs were associated with reduced weight through 17 years of age among girls but not among boys. Tri-ortho-substituted PCBs were marginally associated with increased height in boys. Although limited by sample size, our results suggest that prenatal exposure to PCBs may affect growth, especially in girls, and that ortho-substitution is an important determinant of its effect on growth.
Human Semilunar Cardiac Valve Remodeling by Activated Cells From Fetus to Adult
Authors: Elena Aikawa, Peter Whittaker, Mark Farber, Karen Mendelson, Robert F. Padera, Masanori Aikawa, Frederick J. Schoen
Journal: Circulation (2006)

Background— The evolution of cell phenotypes and matrix architecture in cardiac valves during fetal maturation and postnatal adaptation through senescence remains unexplored. Methods and Results— We hypothesized that valvular interstitial (VIC) and endothelial cell (VEC) phenotypes, critical for maintaining valve function, change throughout life in response to environmental stimuli. We performed quantitative histological assessment of 91 human semilunar valves obtained from fetuses at 14 to 19 and 20 to 39 weeks’ gestation; neonates minutes to 30 days old; children aged 2 to 16 years; and adults. A trilaminar architecture appeared by 36 weeks of gestation but remained rudimentary compared with that of adult valves. VECs expressed an activated phenotype throughout fetal development. VIC density, proliferation, and apoptosis were significantly higher in fetal than adult valves. Pulmonary and aortic fetal VICs showed an activated myofibroblast-like phenotype (α-actin expression), abundant embryonic myosin, and matrix metalloproteinase-collagenases, which indicates an immature/activated phenotype engaged in matrix remodeling versus a quiescent fibroblast-like phenotype in adults. At birth, the abrupt change from fetal to neonatal circulation was associated with a greater number of α-actin–positive VICs in neonatal aortic versus pulmonary valves. Collagen content increased from early to late fetal stages but was subsequently unchanged, whereas elastin significantly increased postnatally. Collagen fiber color analysis revealed a progressive temporal decrease in thin fibers and a corresponding increase in thick fibers. Additionally, collagen fibers were more aligned in adult than fetal valves. Conclusions— Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become quiescent, whereas collagen matures, which suggests a progressive, environmentally mediated adaptation.
Paracolic Fistulous Tracts in Diverticulitis and Granulomatous Colitis
Authors: Richard H. Marshak
Journal: JAMA (1980)

GRANULOMATOUS colitis may involve any portion of the large bowel. Although an extensive length of intestine is diseased in many cases, segmental lesions are not uncommon. When segmental disease occurs in patients of middle or old age, it may involve a portion of the colon, usually the sigmoid, where multiple diverticula are also present. Difficulty then arises in differentiating granulomatous colitis from diverticulitis. An unusual feature of both diseases is the presence of a paracolic fistulous tract. Paracolic longitudinal tracts of the sigmoid were originally thought to be secondary only to diverticulitis. In 1970 we<sup>1</sup>reported that paracolic longitudinal tracts also occur in granulomatous colitis, usually in association with diverticula. It was suggested that the transverse fissures of Crohn's disease penetrate the mucosal herniations of the diverticula to produce fistulous tracts. We also postulated that when the tract exceeded 10 cm in length, its presence was pathognomonic for granulomatous colitis.
C-peptide suppression test and sulphonylurea-induced factitious hypoglycaemia.
Authors: J S Harrop, P R Golding, P Goodall, V M Leveau, G A Steele, A R Ingle
Journal: BMJ (1982)

Total thyroidectomy is a special situation in which the effect of T3 on the secretion of thyroid-stimulating hormone can be studied
Dysplastic nevi, cutaneous melanoma, and other skin neoplasms in patients with myotonic dystrophy type 1: A cross-sectional study
Authors: Anna Zampetti, Gabriella Silvestri, Simona Manco, Katy Khamis, Marcella Masciullo, Maria Laura Ester Bianchi, Antonello Damiani, Massimo Santoro, Dennis Linder, Anthony Bewley, Claudio Feliciani
Journal: Journal of the American Academy of Dermatology (2014)
Method of Relaxation
Authors: Alfred P. French
Journal: JAMA (1973)

To the Editor.—  We have developed a simple, effective, meditation-like relaxation method that may be taught within a few minutes and is helpful in the management of insomnia, moderate anxiety states, and relief of moderate pain. In essence, the method utilizes self-directed awareness that facilitates development of a pleasantly relaxing and easily maintained state similar to meditation. The method consists of three steps: (1) muscular relaxation and passive breathing; (2) allowing the mind to drift in the direction of a very pleasant and restful memory; (3) presenting the memory to the mind in a manner that effortlessly focuses attention on the memory.  The instructions for the three steps are approximately as follows: The patient sits in a comfortable position with both feet on the floor and with eyes closed. He is instructed to allow his breathing to become very relaxed and natural, and to simply allow the air to flow
Serving Patients Who May Die Soon and Their Families
Authors: Michael W. Rabow
Journal: JAMA (2001)

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