tbuckley/cabot-search huggingface dataset:
Effect of short-term systemic glucocorticoid treatment on human nasal mediator release after antigen challenge.
Authors: U Pipkorn, D Proud, L M Lichtenstein, R P Schleimer, S P Peters, N F Adkinson, A Kagey-Sobotka, P S Norman, R M Naclerio
Journal: Journal of Clinical Investigation (1987)

The effect of systemic glucocorticoid treatment on early- and late-phase nasal allergic reactions after allergen challenge was determined in a double-blind, cross-over study in 13 allergic individuals. The subjects were pretreated for 2 d before challenge with 60 mg prednisone per day or a matching placebo. A previously described model using repeated nasal lavages for measuring mediator release in vivo was utilized. Symptom scores obtained repeatedly before, during, and after the challenge and the number and timing of sneezes were recorded. The mediators measured were histamine. N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity, kinins, PGD2, and LTC4/D4. Albumin was also measured as a marker of plasma transudation. Blood samples were taken for determination of total number of white blood cells, differential count, and total blood histamine content. No effect of steroid therapy was found on the appearance of symptoms or any of the mediators, except a reduction in kinins, in the early phase of the allergic reaction. However, in the late phase, the prednisone reduced the number of sneezes (P less than 0.01), as well as the level of histamine (P less than 0.05), TAME-esterase activity (P less than 0.05), kinins (P less than 0.05), and albumin (P less than 0.05). Only low levels of leukotrienes were found in the late phase, but the quantities of these mediators seemed to be decreased by the glucocorticoid treatment (P = 0.06). PGD2 did not increase during the LPR and thus was not affected by glucocorticosteroids. The immediate response to a second challenge 11 h after the first was also evaluated. Whereas the appearance of mediators was enhanced over the initial response to the same challenge dose in placebo-treated subjects, this enhancement was abrogated after prednisone treatment. As this dose of drug is known to be clinically effective in treating hay fever, the present study confirms the earlier findings of others that short-term systemic glucocorticoid treatment inhibits the late phase but not the immediate phase of antigen challenge. Furthermore, secondary enhancement of immediate responses is inhibited. This study shows that glucocorticoids inhibit the generation or release of inflammatory mediators during the late reaction and the physiologic response.
Tragedies From Drug Therapy for Health Professionals
Authors: Robert C. Hastings
Journal: JAMA (1985)

In a sensationalistic style, Ronald B. Stewart, professor and chairman of the department of pharmacy practice of a college of pharmacy, has compiled 11 instances in which untoward effects of a marketed drug have led to the withdrawal of that drug from the market. Each instance takes up a chapter, which usually begins with a quotation implying the virtues of therapeutic nihilism. A brief review of the standard pharmacology of the drug is then given in quasi-lay language, followed by a dramatic recounting of the discovery of the untoward effect, in which indictments are freely thrown at the pharmaceutical industry, regulatory agencies, practicing physicians, and anyone else involved in the drug's development and marketing. Next, Stewart ghoulishly illustrates the untoward effect (ranging from tooth discoloration from tetracyclines to thalidomide-induced phocomelia). He details the litigation and settlements in each instance, leaving the reader with a feeling that the "punishment" was inadequate
A novel polymorphism of the human CD40 receptor with enhanced function
Authors: Anna L. Peters, Robert M. Plenge, Robert R. Graham, David M. Altshuler, Kathy L. Moser, Patrick M. Gaffney, Gail A. Bishop
Journal: Blood (2008)

Abstract CD40 signaling is critical for innate and adaptive immunity against pathogens, and the cytoplasmic domain of CD40 is highly conserved both within and between species. A novel missense single nucleotide polymorphism (SNP) in the cytoplasmic domain of CD40 at position 227 (P227A) was identified, which resides on a conserved ancestral haplotype highly enriched in persons of Mexican and South American descent. Functional studies indicated that signaling via human (h) CD40-P227A stably expressed in several B-cell lines led to increased phosphorylation of c-Jun, increased secretion of the pro-inflammatory cytokines interleukin (IL)–6 and TNF-α, and increased Ig production, compared with wild-type hCD40. Cooperation between hCD40-P227A signaling and B-cell receptor (BCR)– or Toll-like receptor 9 (TLR9)–mediated signaling was also enhanced, resulting in elevated and synergistic production of IL-6 and Ig. We have thus identified a novel genetic variant of hCD40 with a gain-of-function immune phenotype.
Oral cladribine was more effective than placebo for relapsing–remitting multiple sclerosis
Authors: James Hughes
Journal: Annals of Internal Medicine (2010)

ACP Journal Club18 May 2010Oral cladribine was more effective than placebo for relapsing–remitting multiple sclerosisJames Hughes, MDJames Hughes, MDTamworth Rural Referral Hospital, Tamworth, New South Wales, Australia (J.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-10-201005180-02008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGiovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362:416-26. https://pubmed.ncbi.nlm.nih.gov/20089960Clinical Impact RatingsGIM/FP/GP: Neurology: References1 Biogen Idec Australia. Tysabri (natalizumab) safety update, 17 Mar 2010. Google Scholar2 Thompson JP, Noyes K, Dorsey ER, Schwid SR, Holloway RG. Quantitative risk–benefit analysis of natalizumab. Neurology. 2008;71:357-64. [PMID: 18663181] Google Scholar3 Hughes B. First oral therapies for multiple sclerosis anticipated. Nat Rev Drug Discov. 2009;8:831-3. [PMID: 19876030]. Google Scholar4 EMD Serono. Novantrone: mitoxantrone for injection concentrate, additional safety information, Apr 2005. www.novantrone.com/assets/pdf/healthcare_professional_letter.pdf (accessed 23 Mar 2010). Google Scholar5 Zivadinov R, Sepcic J, Nasuelli D, et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing–remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001;70:773-80. [PMID: 11385012] Google Scholar Author, Article, and Disclosure InformationAffiliations: Tamworth Rural Referral Hospital, Tamworth, New South Wales, Australia (J.H.)This article was published at Annals.org on 4 May 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOral fingolimod was more effective than intramuscular interferon for relapsing–remitting multiple sclerosis James Hughes Oral fingolimod was more effective than placebo for relapsing–remitting multiple sclerosis James Hughes Metrics 18 May 2010Volume 152, Issue 10Page: JC5-8KeywordsDisabilitiesDrugsInterferonsLesionsMagnetic resonance imagingMonoclonal antibodiesMultiple sclerosisQuantitative analysisSafetySerious adverse events ePublished: 18 May 2010 Issue Published: 18 May 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Lead in Bones and Drinking Water in Towns with Hard and Soft Water
Authors: M. D. Crawford, D. G. Clayton
Journal: BMJ (1973)

In two comparable series of medicolegal necropsies the lead content of ribs was found to be much higher in three soft water than in three hard water towns in England and Wales. Fourteen out of 96 "overnight" tap water samples from five soft water and five hard water towns in England and Wales and from Glasgow (soft water) had lead concentrations of over 0.1 p.p.m.; values over 0.3 p.p.m. were found only in Glasgow. The possible relevance of the findings to the association of cardiovascular disease and soft drinking water is discussed.
Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Intramural and Extraintestinal Mass Lesions: Diagnostic Accuracy, Complication Assessment, and Impact on Management
Authors: V. K. Chen, M. A. Eloubeidi
Journal: Endoscopy (2005)

The aims of this study were: firstly, to determine the usefulness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in obtaining tissue diagnosis of intramural and extraintestinal lesions; secondly, to assess the immediate, acute, and 30-day complications in these patients; and thirdly, to assess the impact of the tissue diagnoses on patient management.All EUS-FNAs of extraintestinal mass lesions and intramural gastrointestinal tumors over a 26-month period were evaluated prospectively. The reference standards for the final diagnosis were surgery (n = 20), repeat imaging (n = 12), clinical follow-up (n = 4), or death from disease (n = 2). Four patients were lost to follow-up.Forty-two consecutive patients (24 men, 18 women; mean age 59.7 years) underwent EUS-FNA of extraintestinal mass lesions and intramural gastrointestinal tumors. Previous attempts at tissue diagnosis had failed in 52.4 % of the patients. The EUS-FNA cytological diagnoses included: 17 gastrointestinal stromal tumors, five esophageal cancers, five rectal cancers, one bronchogenic cyst, one foregut duplication cyst, and 13 other miscellaneous diagnoses. The mean number of passes needed to reach a diagnosis was 3.9 (+/- 2.2). The mean follow-up period was 13.1 months. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA of extraintestinal and intramural tumors were 97 %, 100 %, 100 %, 90 %, and 98 %, respectively. No major complications were encountered.EUS-FNA is a safe and accurate method that can provide a tissue diagnosis in intramural and extraintestinal mass lesions, especially when other modalities have failed. EUS-FNA significantly affects the management of patients by allowing them to be allocated to appropriate treatment and by avoiding the need for more invasive procedures to obtain tissue diagnosis.
Alcohol, Nutrient Intake, and Hypertension-Reply
Authors: H. W. Gruchow
Journal: JAMA (1985)

In Reply.—  We agree with Dr Holden that sodium intake probably has a much greater effect on blood pressures in salt-sensitive persons than in others. However, this does not rule out the possibility that higher sodium intakes contribute to elevated blood pressures in nonsensitive persons or that sodium might interact with other nutrients to increase blood pressures. The objective of our study was to assess the relative importance of dietary factors. Our analysis identified sodium as the nutrient having the strongest association with systolic blood pressure for the total study cohort and alcohol and sodium as having the strongest associations with systolic blood pressure for drinkers.  Although a probability of less than 05 is footnoted in the tables displaying these results, the actual probability for the sodium-blood pressure association for the total study cohort is P =.00064 ( F =11.675, with 1 and 9,549 df ); for drinkers, P =.000007 ( F =20.193, with
Annular injuries following the insertion of heart valve prostheses
Authors: V. F. Bowes, B. N. Datta, M. D. Silver, J. A. Minielly
Journal: Thorax (1974)

<b>Bowes, V. F., Datta, B. N., Silver, M. D. and Minielly, J. A. (1974).</b><i>Thorax</i>, <b>29</b>, 530-533. <b>Annular injuries following the insertion of heart valve prostheses.</b> The clinical presentation and morphological findings in eight cases of annular injury associated with the insertion of prosthetic heart valves are discussed. The lesions presented as a separation of the left atrium and ventricle at the mitral annulus (one patient), a sinus or false aneurysm in the left posterior atrioventricular groove (two patients), or as a separation of the aortic root from the base of the heart (five patients). The pathogenesis of the lesions is similar. Annular tissue was weakened either by the removal of excess tissue or by an abnormal stress placed on normal tissue or by a slight stress placed on tissue altered by disease, and, as a result, it separated or tore. The resultant haemorrhage either caused the patient9s death or, with time, produced the other morphological findings. Factors predisposing patients to the injuries are discussed and a differential diagnosis of annular pseudoaneurysms is provided.
A prospective evaluation of the Björk-Shiley, Hancock, and Carpentier-Edwards heart valve prostheses.
Authors: P Bloomfield, A H Kitchin, D J Wheatley, P R Walbaum, W Lutz, H C Miller
Journal: Circulation (1986)

From 1975 to 1979, 540 patients undergoing valve replacement were entered into a randomized trial and received either a Björk-Shiley (273 patients) or a porcine heterograft prosthesis (initially a Hancock valve [107 patients] and later a Carpentier-Edwards prosthesis [160 patients]). Two hundred and sixty-two patients required mitral valve replacement, 210 required aortic valve replacement, 60 required mitral and aortic valve replacement, and eight also required associated tricuspid valve replacement (six mitral valve replacement; two mitral plus aortic valve replacement). Analysis of 34 preoperative and operative variables showed the treatment groups to be well randomized. In-hospital mortality was not significantly different among patients receiving the three prostheses for aortic valve replacement (7.6% overall) and mitral plus aortic valve replacement (10% overall), but there was a higher in-hospital mortality for patients undergoing mitral valve replacement with the Carpentier-Edwards prosthesis (15.5% compared with 8.8% overall; p = .03). This difference could not be explained on the basis of any preoperative or operative variable. Median follow-up was 5.6 (range 2.8 to 8.3) years. Actuarial survival after mitral valve replacement was 56.7 +/- 7.0% at 7 years, that after aortic valve replacement was 69.6 +/- 9.6% at 7 years, and that after mitral plus aortic valve replacement was 62.5 +/- 20.0% at 7 years. There was no significant difference in actuarial survival of patients receiving the three prostheses within the mitral, aortic, and mitral plus aortic valve replacement groups, nor was there a difference when these groups were amalgamated. Thirty-seven patients required reoperation for valve failure (15 with Björk-Shiley, 12 with Hancock, and 10 with Carpentier-Edwards valves; p = NS) and 11 died at reoperation (four with Björk-Shiley, four with Hancock, and three with Carpentier-Edwards valves; overall operative mortality 29.7%). Up to 7 years after surgery, there was no significant difference in the incidence of thromboembolism in patients with different prostheses undergoing mitral or aortic valve replacement. There were too few patients undergoing mitral plus aortic valve replacement for meaningful comparison. There was no significant beneficial effect of anticoagulants in patients undergoing mitral or aortic valve replacement with porcine prostheses, but patients were not randomly allocated to anticoagulant treatment. All patients with Björk-Shiley prostheses received anticoagulants.(ABSTRACT TRUNCATED AT 400 WORDS)
Tl-201 Scintigraphy in Muscle Trauma
Authors: CLAYTON J. FRATER, I. PROVAN C. MURRAY, MONICA ROSSLEIGH
Journal: Clinical Nuclear Medicine (2001)

Muscle uptake of Tl-201 thallous chloride in the larger or more major groups, particularly the legs, chest, and upper limb areas, is not uncommonly observed in healthy persons. However, as illustrated in three patients, such uptake, when localized or asymmetric, may provide evidence of unrecognized traumatized muscle, resulting from more chronic or subacute muscle overuse than the acute muscle insult that produces the marked uptake of Tc-99m phosphates associated with frank rhabdomyolysis.
Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm
Authors: Wendie A. Robbins, Marvin L. Meistrich, Dan Moore, Fredrick B. Hagemeister, Heinz-Ulrich Weier, Michael J. Cassel, Gene Wilson, Brenda Eskenazi, Andrew J. Wyrobek
Journal: Nature Genetics (1997)
Druggable targets in pediatric neurocutaneous melanocytosis: Molecular and drug sensitivity studies in xenograft and ex vivo tumor cell culture to identify agents for therapy
Authors: Yibing Ruan, Anna Kovalchuk, Aarthi Jayanthan, Xueqing Lun, Yoji Nagashima, Olga Kovalchuk, James R. Wright, Alfredo Pinto, Adam Kirton, Ronald Anderson, Aru Narendran
Journal: Neuro-Oncology (2014)

Neurocutaneous melanocytosis (NCM) is a rare congenital disorder that presents with pigmented cell lesions of the brain or leptomeninges in children with large or multiple congenital melanocytic nevi. Although the exact pathological processes involved are currently unclear, NCM appears to arise from an abnormal development of melanoblasts or melanocyte precursors. Currently, it has an extremely poor prognosis due to rapid disease progression and lack of effective treatment modalities. In this study, we report on an experimental approach to examining NCM cells by establishing subcutaneous tumors in nude mice, which can be further expanded for conducting molecular and drug sensitivity experiments. Analysis of the NRAS gene-coding sequences of an established NCM cell line (YP-MEL) and NCM patient cells revealed heterogeneity in NRAS Q61K that activated mutation and possibly consequential differential sensitivity to MEK inhibition. Gene expression studies were performed to compare the molecular profiles of NCM cells with normal skin fibroblasts. In vitro cytotoxicity screens of libraries of targeted small-molecule inhibitors revealed prospective agents for further evaluation. Our studies provide an experimental platform for the generation of NCM cells for preclinical studies and the production of molecular and in vitro data with which to identify druggable targets for the treatment.
Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity
Authors: Yujin Shuto, Tamotsu Shibasaki, Asuka Otagiri, Hideki Kuriyama, Hisayuki Ohata, Hideki Tamura, Jun Kamegai, Hitoshi Sugihara, Shinichi Oikawa, Ichiji Wakabayashi
Journal: Journal of Clinical Investigation (2002)

Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake. GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary. Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach. Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown. We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. Tg rats had lower body weight and less adipose tissue than did control rats. Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats. GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats. These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity.
ED-11 * DEMOGRAPHIC, CLINICAL AND SURVIVAL FEATURES OF CHILDHOOD CENTRAL NERVOUS SYSTEM TUMORS IN ISTANBUL UNIVERSITY, ONCOLOGY INSTITUTE DURING 22 YEARS (1990-2012)
Authors: R. Kebudi, E. Darendeliler, O. Gorgun, F. Y. Agaoglu, D. Uludag, I. Ayan
Journal: Neuro-Oncology (2014)

OBJECTIVES: The aim of this study is to identify demographic, clinical and survival features of childhood central nervous system (CNS) tumors admitted to Istanbul University, Oncology Institute, Pediatric Hematology-Oncology in 22 years. METHODS: Charts of patients <19 years admitted were evaluated retrospectively. (Istanbul University Cerrahpasa Medical Faculty Clinical Trials, Ethics Committee no. 83045809-3507). RESULTS: CNS tumors (n = 494) comprised 20,5 % of the 2413 children with cancer, diagnosed between 1990-2012. Male/female:1,25. Median age was 6,5 years (0.13-18yrs). 51 patients had NF1, 4 had tuberosclerosis. Distrubution according to histopathology/diagnosis was as follows: 35 % (n = 173) Medulloblastoma and other embryonal tumors, 17% (n = 84) astrocytoma other than optic gliomas, 16,5% (n = 82) ependymoma and choroid plexus tumors, 14% (n = 69) optic glioma, and 12,8% (n = 63) diffuse pontine gliomas. 5-yrs and 10-yrs overall survival (OS) in the whole group were 61% and 55,4% respectively. 29,6 % of the patients had metastasis in the CSF and/or the spinal axis and/or gross residual tumor, these had 5-yrs and 10-yrs OS of 36,5% and 27,2 %, whereas the rest had 5-yrs and 10-yrs OS are 73% and 68,9% (p < 0,001). Medulloblastoma and other embryonal tumors had 5-yrs and 10-yrs OS 58,4% and 57,5% . Ependymoma and choroid plexus carcinomas had 5-yrs and 10-yrs OS of 48,4% and 31,4%. Low grade and high grade astrocytomas had 10-yrs OS of 95 % and 40% respectively (p < 0,001). Second tumors were diagnosed in two medulloblastoma patients, one malignant nerve sheath tumor at 9 years, a case with concurrent high glade glioma and mediastinal lymphoblastic lymphoma at 3,5 years. CONCLUSIONS: The most common solid tumor in our cohort, similar to developed countries, was CNS tumors. Embryonal tumors comprised the majority of the CNS tumors treated in our institution. 5 year survival was 61 %. These children should be followed up for late effects including second tumors.
AGGLUTINATION OF TYPHOID GROUP OF ORGANISMS IN CASES OF JAUNDICE AMONG VACCINATED PERSONS
Authors: HENRY J. NICHOLS
Journal: JAMA (1923)

In recent years an unusual number of cases of jaundice, sometimes in epidemics, have come under the care of American physicians, especially in the Northeastern states. The most recent report is that by Bloomer, 1 which expresses the current opinion that the disease is an infection due to some specific organism at present unknown. The same increase in cases of jaundice has been reflected in the army, without, however, the occurrence of any definite epidemics, so far as I know. Sporadic cases have occurred in a number of stations in the Second Corps Area, which includes New York, New Jersey and Delaware. In the course of an investigation of this disease, one positive finding has been made, which, it is thought, should be recorded.  A number of cases have shown, in the blood serum, a definite agglutination of paratyphoid B bacilli, with a less marked agglutination of typhoid and paratyphoid