tbuckley/cabot-search huggingface dataset:
HYPERSENSITIVITY TO EPHEDRINE AND EPHETONINE
Authors: Michael Zeller
Journal: JAMA (1933)

In 1923, Chen and Schmidt recommended the use of ephedrine in the treatment of hay fever, asthma and hypotension. Since then, considerable has been written regarding the therapeutic efficacy of the drug but very little mention has been made of the unfavorable effects that it may produce. Scheer,<sup>1</sup>in 1929, was the first to report a case of dermatitis venenata of the nose and upper lip resulting from the local application of ephedrine in oil. Ramirez and Eller<sup>2</sup>observed four cases of contact dermatitis due to ephedrine. In 1931, Ayres and Anderson<sup>3</sup>reported similar cases following nasal and oral administration of ephedrine, but their cases presented, in addition, generalized scarlatiniform eruptions. Bullen, Frances and Parker,<sup>4</sup>in 1932, reported two cases of dermatitis medicamentosa due to ephedrine. Following is the report of a case of dermatitis venenata due to nasal application of ephedrine inhalant: <h3>REPORT OF CASE</h3>
HER2 Overexpression Renders Human Breast Cancers Sensitive to PARP Inhibition Independently of Any Defect in Homologous Recombination DNA Repair
Authors: Somaira Nowsheen, Tiffiny Cooper, James A. Bonner, Albert F. LoBuglio, Eddy S. Yang
Journal: Cancer Research (2012)

HER2 overexpression in breast cancer confers increased tumor aggressiveness. Although anti-HER2 therapies have improved patient outcome, resistance ultimately occurs. PARP inhibitors target homologous recombination (HR)-deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we show that HER2+ breast cancers are susceptible to PARP inhibition independent of an HR deficiency. HER2 overexpression in HER2 negative breast cancer cells was sufficient to render cells susceptible to the PARP inhibitors ABT-888 and AZD-2281 both in vitro and in vivo, which was abrogated by HER2 reduction. In addition, ABT-888 significantly inhibited NF-κB (p65/RelA) transcriptional activity in HER2+ but not HER2 negative breast cancer cells. This corresponded with a reduction in phosphorylated p65 and total IKKα levels, with a concomitant increase in IκBα. Overexpression of p65 abrogated cellular sensitivity to ABT-888, whereas IκBα overexpression reduced cell viability to a similar extent as ABT-888. Therefore, susceptibility of HER2+ breast cancer cells to PARP inhibition may be because of inhibition of NF-κB signaling driven by HER2. Our findings indicate that PARP inhibitors may be a novel therapeutic strategy for sporadic HER2+ breast cancer patients.
Mycophenolate mofetil: A new therapeutic option in the treatment of blistering autoimmune diseases
Authors: Marcella Grundmann-Kollmann, Hans Christian Korting, Stefanie Behrens, Peter Kaskel, Ulrike Leiter, Gertraud Krähn, Martina Kerscher, Ralf Uwe Peter
Journal: Journal of the American Academy of Dermatology (1999)
Phase I Study of Vincristine, Irinotecan, and 131I-Metaiodobenzylguanidine for Patients with Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial
Authors: Steven G. DuBois, Louis Chesler, Susan Groshen, Randall Hawkins, Fariba Goodarzian, Hiroyuki Shimada, Greg Yanik, Michael Tagen, Clinton Stewart, Yael P. Mosse, John M. Maris, Denice Tsao-Wei, Araz Marachelian, Judith G. Villablanca, Katherine K. Matthay
Journal: Clinical Cancer Research (2012)

Abstract Purpose:131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical with activity in patients with relapsed or refractory neuroblastoma. Irinotecan is a known radiosensitizer with activity in neuroblastoma. This phase I study aimed to determine the recommended phase 2 dose of MIBG together with fixed doses of vincristine and irinotecan. Experimental Design: Patients 1 to 30 years old with relapsed or refractory neuroblastoma and MIBG-avid tumors were eligible. All patients had autologous hematopoietic stem cells (PBSC) available and met standard phase I organ function requirements. Irinotecan (20 mg/m2/dose IV) was given on days 0 to 4 and 7 to 11, with vincristine (1.5 mg/m2 IV) on days 0 and 7. MIBG was given on day 1 following a 3 + 3 phase I dose escalation design starting at 8 mCi/kg MIBG. PBSCs were administered at dose level 8 mCi/kg for prolonged myelosuppression and for all patients at 12 mCi/kg or more. Results: Twenty-four patients evaluable for dose escalation (median age, 6.7 years; range, 1.9–26.8 years) received 1 (n = 17), 2 (n = 5), or 3 (n = 2) cycles of therapy. Myelosuppression and diarrhea were the most common toxicities. Two of 6 patients at the 18 mCi/kg dose level had dose-limiting toxicity (DLT), including one with protocol-defined DLT with prolonged mild aspartate aminotransferase elevation. Eighteen mCi/kg was the recommended phase 2 dose. Six additional patients were treated at 18 mCi/kg, with one additional DLT. Responses (2 complete and 4 partial responses) occurred in 6 of 24 (25%) evaluable patients. Conclusions: MIBG is tolerable and active at 18 mCi/kg with standard doses of vincristine and irinotecan. Clin Cancer Res; 18(9); 2679–86. ©2012 AACR.
Quality of Life Outcomes From a Randomized Phase III Trial of Cisplatin With or Without Topotecan in Advanced Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Bradley J. Monk, Helen Q. Huang, David Cella, Harry J. Long
Journal: Journal of Clinical Oncology (2005)

To prospectively assess the impact of treatment with cisplatin alone or in combination with topotecan (CT) on quality of life (QOL) in patients with advanced or recurrent cervical cancer, and to explore the prognostic value of baseline QOL scores.Patients entered on Gynecologic Oncology Group (GOG) Protocol 179 were expected to complete QOL assessments at four time points using Functional Assessment of Cancer Therapy-General (FACT-G), Cervix subscale (Cx subscale), FACT/GOG-Neurotoxicity subscale (NTX subscale), Brief Pain Inventory (BPI), and UNISCALE (UNI). Adjusting for patient age, baseline scores, and effects of time, we longitudinally examined treatment effect on QOL during and after chemotherapy.Among patients randomly allocated to receive cisplatin (n = 146) or CT (n = 147), there were no statistically significant differences in QOL up to 9 months after randomization despite more hematologic toxicity in the combination arm. QOL assessments were completed at rates of 98%, 85%, 68%, and 59%, respectively, for the four time points, with similar rates and reasons for nonparticipation between regimens. Baseline FACT-G (P = .0016) and BPI (P = .0001) scores were significantly associated with patient age; older patients had better QOL and less pain. Baseline UNI was positively correlated with FACT-G (r = 0.66; P < .001) and Cx subscale (r = 0.29; P < .001), and negatively related to BPI (r = -0.41; P < .0001). Baseline FACT-Cx (FACT-G + Cx subscale) was associated with survival.Despite increased toxicity, CT did not significantly reduce patient QOL when compared with cisplatin alone. Patient-reported QOL measures may be an important prognostic tool in advanced cervix cancer.
RupturedKlebsiella pneumoniae liver abscess after high-dose cyclophosphamide for severe aplastic anemia
Authors: Je-Jung Lee, Hyeoung-Joon Kim, Ik-Joo Chung, Hoon Kook, Moo-Rim Park, Chan-Jong Kim, Dong-Hyeon Shin, Tai-Ju Hwang
Journal: American Journal of Hematology (2000)

A 19-year-old woman with severe aplastic anemia who had previously failed antithymocyte globulin/cyclosporine A received high-dose cyclophosphamide without bone marrow rescue. On day +14, she complained of right upper quadrant abdominal pain and fever. A CT scan of the abdomen showed multiple liver abscesses with rupture and Klebsiella pneumoniae was isolated from blood. In spite of aggressive antibiotic therapy, she rapidly deteriorated and died of overwhelming sepsis. To our knowledge, our patient is the first case of fatal ruptured liver abscess after high-dose cyclophosphamide in a patient with severe aplastic anemia. Am. J. Hematol. 64:218–220, 2000. © 2000 Wiley-Liss, Inc.
Book Review Antibiotic Optimization: Concepts and Strategies In Clinical Practice (Infectious Disease and Therapy. Vol. 33.) Edited by Robert C. Owens, Jr., Paul G. Ambrose, and Charles H. Nightingale. 663 pp. New York, Marcel Dekker, 2005. $179.95. 0-8247-5431-X
Authors: David R. Snydman, Kenneth R. Lawrence
Journal: New England Journal of Medicine (2005)
Nationwide, Prospective Registration of Type 1 Diabetes in Children Aged &amp;lt;15 Years in Norway 1989–1998
Authors: Geir Joner, Lars C. Stene, Oddmund Søvik
Journal: Diabetes Care (2004)

OBJECTIVE—An increasing incidence rate of childhood-onset type 1 diabetes has been described in several countries, particularly among the youngest children, and the Nordic countries have consistently been shown to have the highest incidence rates. An increasing incidence had previously been reported in Norway for 1973–1982, together with regional variation within the country. The aim of this study was to test whether there has been an increasing incidence of type 1 diabetes and a continued regional variation among children aged &amp;lt;15 years in Norway during 1989–1998. RESEARCH DESIGN AND METHODS—As a part of the activities of the National Childhood Diabetes Registry of Norway and the EURODIAB study, a 10-year prospective, nationwide case registration of type 1 diabetes was done among children aged &amp;lt;15 years. RESULTS—A total of 1,867 new case subjects (1,009 boys and 858 girls) were identified. The total incidence rate was 22.4 per 100,000 person-years (95% CI 21.5–23.5). The incidence was 13.1, 26.3, and 28.8 per 100,000 in the age-groups 0–4.9, 5–9.9, and 10–14.9 years, respectively. No increase or decrease over time was detected in any of the age-groups during the 10-year period. We found significant variation between the 19 counties, which only partly reflected the pattern previously described for 1973–1982. CONCLUSIONS—We found a significant regional variation within Norway. After a previous period of increase, the incidence has been stable in all age-groups &amp;lt;15 years during 1989–1998.
Psychological Reactions to Medical Procedures
Authors: Jenifer Wilson-Barnett
Journal: Psychotherapy and Psychosomatics (1992)

Many medical procedures evoke anxiety and discomfort. Despite substantial research effort showing the efficacy of psychological interventions, there is abundant evidence that patients remain inadequately prepared. This review of well-tried approaches demonstrates that varied interventions are required to reduce stress and discomfort and outlines ways in which staff should apply the research findings.
Hierarchy of Notch–Delta interactions promoting T cell lineage commitment and maturation
Authors: Valerie Besseyrias, Emma Fiorini, Lothar J. Strobl, Ursula Zimber-Strobl, Alexis Dumortier, Ute Koch, Marie-Laure Arcangeli, Sophie Ezine, H. Robson MacDonald, Freddy Radtke
Journal: The Journal of Experimental Medicine (2007)

Notch1 (N1) receptor signaling is essential and sufficient for T cell development, and recently developed in vitro culture systems point to members of the Delta family as being the physiological N1 ligands. We explored the ability of Delta1 (DL1) and DL4 to induce T cell lineage commitment and/or maturation in vitro and in vivo from bone marrow (BM) precursors conditionally gene targeted for N1 and/or N2. In vitro DL1 can trigger T cell lineage commitment via either N1 or N2. N1- or N2-mediated T cell lineage commitment can also occur in the spleen after short-term BM transplantation. However, N2–DL1–mediated signaling does not allow further T cell maturation beyond the CD25+ stage due to a lack of T cell receptor β expression. In contrast to DL1, DL4 induces and supports T cell commitment and maturation in vitro and in vivo exclusively via specific interaction with N1. Moreover, comparative binding studies show preferential interaction of DL4 with N1, whereas binding of DL1 to N1 is weak. Interestingly, preferential N1–DL4 binding reflects reduced dependence of this interaction on Lunatic fringe, a glycosyl transferase that generally enhances the avidity of Notch receptors for Delta ligands. Collectively, our results establish a hierarchy of Notch–Delta interactions in which N1–DL4 exhibits the greatest capacity to induce and support T cell development.
Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model.
Authors: K Ohzono, S Koyanagi, Y Urabe, Y Harasawa, H Tomoike, M Nakamura
Journal: Circulation Research (1986)

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 +/- 0.5 g (mean +/- SEM) in the right ventricle and 10.5 +/- 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 +/- 0.7 g in the right ventricle and 5.2 +/- 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 +/- 0.06 and 0.28 +/- 0.05 in the right and left ventricles, respectively (p less than 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 +/- 0.04 in the right ventricle and 0.32 +/- 0.06 in the left ventricle (p less than 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.
Erythema Chronicum Migrans and "Lyme Arthritis"
Authors: Gerald W. Hazard
Journal: JAMA (1976)

To the Editor.—  During the summer of 1975, we saw two children in Hyannis with severe myalgia and expanding annular lesions that fit the description of the erythema chronicum migrans. Both these patients, aged 9 and 11 years, had difficulty walking because of the myalgia associated with their illness. Because of their contact with saltwater swimming around fish piers, the diagnosis of erysipeloid (fish-handlers disease) was entertained. Subsequently, we learned that after the children returned home (one to Newington, Conn, and one to Winchester, Mass) transient arthritis developed in both.  In retrospect, these two children may well have had the new form of arthritis recently described in Lyme, Conn. Our experience was the reverse of the Connecticut group; we saw the rash and not the subsequent arthritis.
Frontal Plane Studies of Homogeneous Torso Models
Authors: ERNEST FRANK, CALVIN F. KAY
Journal: Circulation (1954)

The accuracy of currently used vector methods of analysis of frontal-plane electrocardiograms and the behavior of the Wilson central-terminal voltage are investigated experimentally by means of an accurate unipolar voltage technic, using human torso models filled with a homogeneous conducting fluid in which is immersed a heart dipole. The errors entailed in the determination of the manifest heart vector from torso surface voltages by means of Einthoven's vector projection methods are found to be very sizable and strongly dependent upon the position of the heart dipole which is placed at various points within the heart volume in this investigation. Einthoven's angle α is found to depart from the actual heart-vector angle by –7 degrees to +41 degrees, at the instant when the manifest heart vector is a maximum, and the amplitude and shape of frontal-plane vector loops and limb leads are found to be considerably distorted, in many cases, as compared with the actual heart-dipole behavior. The Wilson central-terminal voltage is found to depart from its ideal value of zero by approximately 15 to 40 per cent of the maximum value of the manifest heart vector as seen in the frontal plane, in typical cases, and by more than 200 per cent in extreme cases. It is shown that the component of the dipole perpendicular to the frontal plane is not negligible in influencing the limb-electrode potentials. The results are found to be consistent within 10 per cent or better for a male and female torso differing widely in proportions and contour, except for an increase in the female torso voltages arising from its smaller physical dimensions. The results are presented principally in terms of the QRS complex, but the geometric triangle representation is given as are numerical coefficients which describe torso surface voltages.
Prognosis of Atrial Fibrillation in Congestive Heart Failure
Authors: Johan R. Folkeringa, H.J.G.M. Crijns, D.J. Van Veldhuisen
Journal: Circulation (2004)

To the Editor:In a recent issue of Circulation, Wang et al 1 report that incident atrial fibrillation in patients with congestive heart failure carries a poor prognosis.They rightfully argue that early intervention to prevent atrial fibrillation in heart failure patients and to prevent congestive heart failure in patients with atrial fibrillation may importantly improve prognosis in patients suffering from one of these conditions.Previously, in a population with advanced heart failure, we did not find a decreased survival associated with incident atrial fibrillation. 2This suggests that if patients suffer from advanced heart failure without previous atrial fibrillation, strategies aiming at prevention of the arrhythmia may not benefit any survival.How to reconcile these facts?In patients surviving until an advanced stage of heart failure without previous atrial fibrillation, the very onset of atrial fibrillation cannot change the lethal effect of heart failure.This view is supported by the present Framingham analysis indicating that previous or concurrent atrial fibrillation in heart failure subjects does not have an impact on prognosis.We feel these are important observations.The advice to initiate antiarrhythmic strategies in heart failure subjects still in sinus rhythm probably only applies to those with mild to moderate forms of the disease.In this respect, the study by Vermes et al, 3 in the same issue of Circulation, is promising, because it shows that preventing incident atrial fibrillation is feasible.Hopefully, the Atrial Fibrillation and Congestive Heart Failure trial 4 will shed light on the question of which heart failure patients will benefit from primary arrhythmia prophylaxis.Such knowledge may help to avoid needless, inconvenient, and potentially hazardous antiarrhythmic treatment in many patients with heart failure.
CONJUNCTIVITIS IN THE TROPICS
Authors: R. H. Elliot
Journal: BMJ (1925)

THis paper is a plea for the p)erformance of gastAro- *jejunostomy whenever possible at the timie of op)erlatioll for r)erfoeation.Beginninig witih some apprehension, I liave beeni led to do so more anid moic frequently withi inicreasing eIxperlience, an(d L niow regard it as almo.st a rouitine part of the operationi.The cases anialyvsed below are all those I liave treated in hosp)ital since' my retulrn from-l the war: 16 were duodenal, 15 pre-pyloric, 5 in the body of the stomiiach, and( in 4 the situLatioin of tile ulcer is not stated ill the niotes.Tlhere were 38 males anid 2 females.T-eatinent.Every case but one was operated oni.This patienlt w-as mnoribuind on admission, and failed to rally withl treatment.The deatlh is included in the mortality statistics.Ill early cases, seeni wvithin abouit twelve hiours of perforationi, sutuire of the ulcer anid gastro-jejunostomy was performed witlhout drainage of the periitoneum, excel)t in thiree inistances of
Allergens and endotoxin on mothers' mattresses and total immunoglobulin E in cord blood of neonates
Authors: J. Heinrich, G. Bolte, B. Holscher, J. Douwes, I. Lehmann, B. Fahlbusch, W. Bischof, M. Weiss, M. Borte, H-E. Wichmann
Journal: European Respiratory Journal (2002)

The current authors examined whether mite and cat allergen and bacterial endotoxin levels in dust of the mothers' mattresses were associated with cord blood immunoglobulin (Ig)E (CB-IgE) levels in newborns. Data from 1,332 term and normal weight neonates, from an ongoing birth cohort study, influences of life-style related factors on the immune system and the development of allergies in childhood (LISA), with complete information on exposure to biocontaminants in mattress dust and CB-IgE were analysed. Two thirds of CB-IgE were undetectable (<0.35 kU x L(-1)). Thus, 0.35 and 0.45 kU x L(-1) (4th quartile) were chosen as cut-offs. Nonparametric smoothing (generalised additive models) showed statistically significant confounder-adjusted associations between elevated CB-IgE levels (> or = 0.45 kU x L(-1)) and log-transformed exposures to cat (linear), mite (inverse u-shaped), and endotoxin (u-shaped). After adjustment for covariables, elevated CB-IgE levels (logistic regression using the 1st-4th quartiles of exposure) were positively associated with high cat-allergen exposure and medium exposure to mite allergen, but were inversely associated with exposure to endotoxin. The associations were similar, but somewhat weaker, when 0.35 kU x L(-1) was used as cut-off. These results, showing an association between prenatal allergen and endotoxin exposures and immunoglobulin E production, suggest that the development of foetal immune responses may be affected.
PATHOLOGIC EFFECTS OF LACK OF VITAMIN A AND OF ANTI-RACHITIC VITAMIN
Authors: E. V. McCOLLUM
Journal: JAMA (1923)

One of the surprises that have come from nutrition investigations during the last fifteen years is the discovery that certain fats or more complex lipin extracts exert remarkable effects on the nutritive well-being of human beings and animals. Previous to that time, it was believed that fats were of value essentially only as a source of energy. The investigations in this field support the belief that the special role which certain classes of fats derived from various sources exert on metabolism is not due to any component either of the fat molecule as fatty acid or glycerin, or of the molecules of the complex lipin, such as lecithin and kephalin. It seems clear that whatever effects on nutrition are produced by fats are to be attributed to the presence of some substance or substances which are dissolved in the fats and accompany them when extracted from natural foods because of