tbuckley/cabot-search huggingface dataset:
Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase.
Authors: D Sheppard, J E Thompson, L Scypinski, D Dusser, J A Nadel, D B Borson
Journal: Journal of Clinical Investigation (1988)

Substance P and related tachykinins contribute to the airway hyperresponsiveness caused by toluene diisocyanate (TDI) in guinea pigs. Neutral endopeptidase (NEP) is an important modulator of substance P-induced responses. To test the hypothesis that exposure to TDI would increase responsiveness to substance P by inhibiting activity of this enzyme, we determined the dose of substance P required to increase pulmonary resistance by 200% above baseline (PD200) before and after administration of the pharmacologic inhibitor phosphoramidon in guinea pigs studied 1 h after a 1-h exposure to air or 3 ppm TDI. TDI exposure increased responsiveness to substance P significantly. However, phosphoramidon caused a significantly greater leftward shift of the substance P dose-response curve in air-exposed animals than it did in TDI-exposed animals, so that after phosphoramidon, mean values of PD200 in animals exposed to air or TDI did not differ. Tracheal NEP activity was significantly less after exposure to TDI than after exposure to air, whereas activity in the esophagus was the same in both groups. These results suggest that TDI exposure increases the bronchoconstrictor responsiveness of guinea pigs to substance P, in large part through inhibition of airway NEP.
Transmission of Rhinovirus Colds by Self-Inoculation
Authors: J. Owen Hendley, Richard P. Wenzel, Jack M. Gwaltney
Journal: New England Journal of Medicine (1973)

We investigated transmission of rhinovirus colds by examining shedding by infected patients, survival of virus outside the host, and inoculation of susceptible persons. Two of 25 infected persons expelled virus in a cough or sneeze; four of 10 had virus on their hands. Dried rhinovirus could be picked up by the fingers from skin or environmental surfaces. Four of 11 volunteers became infected after touching their nasal or conjunctival mucosa with fingers previously contaminated by rubbing a dried drop of rhinovirus. Adults expose the nasal or conjunctival mucosa to the fingers frequently under natural conditions. Transmission of rhinoviruses from infected to susceptible persons under natural conditions may proceed by transfer of virus from the hands of the infected person to an intermediary surface or directly to the fingers of the susceptible recipient. Infection then results from self-inoculation of eyes or nose with virus on the fingers. (N Engl J Med 288:1361–1364, 1973)
Planning for a Pediatric Disaster — Experience Gained from Caring for 1600 Vietnamese Orphans
Authors: S. Alex Stalcup, Mark Oscherwitz, Martin S. Cohen, Frank Crast, Dan Broughton, Fred Stark, Robert Goldsmith
Journal: New England Journal of Medicine (1975)

The sudden arrival of 1600 Vietnamese orphans in San Francisco required the rapid development of a co-ordinated disaster plan, including the overnight establishment of a 1000-bed pediatric field hospital. The plan required rapid identification and involvement of lay and governmental resources, acute medical triage and provision of ongoing medical care and basic nurturing services and eventual discharge to adoptive families. Because one third of the orphans were under six months of age, conventional nursery resources were insufficient, and a "warehouse" model was implemented. This process required development of a specialized transportation and communication system, the services of 800 physicians, 1400 nurses, and 3200 volunteers and 162 back-up acute hospital beds. Disaster planning in most sizable American cities has focused on the problems of adults. Because of the unusual problem presented by infants and small children, we recommend that cities carefully evaluate their disaster planning with special reference to the needs of children.
Testicle Hemodynamics in Patients after Laparoscopic Varicocelectomy Evaluated Using Color Doppler Sonography
Authors: Vladim&iacute;r &Scaron;tudent, Franti&scaron;ek Z&aacute;tura, Ji&rcaron;&iacute; Scheinar, Radovan Vrtal, Jan Vr&aacute;na
Journal: European Urology (1998)
The humanized SCID mouse model to study HLA class II-linked autoimmunity to desmoglein 3 in pemphigus vulgaris
Authors: T. RAdisch, R. Riechers, M. Hertl
Journal: British Journal of Dermatology (2002)

Summary Background Pemphigus vulgaris (PV) is a severe autoimmmune skin disorder induced by antibodies against desmoglein (Dsg) 3 on epidermal keratinocytes. Objectives To establish an active animal model of PV to analyse the T‐cell‐regulated production of pathogenic antibodies in vivo. Methods Immunodeficient SCID mice were injected with peripheral blood lymphocytes (PBL) from an HLA‐DRB1*0402/DQ8+ patient with PV or a DRB1*0402/DQ8+ healthy donor, with or without subsequent injections of human Dsg3 or preincubation of PBL with Dsg3. Results Human immunoglobulins (2·7–18·5 mg mL−1) were detected in all the mice after 8 weeks. Only one of 30 PBL‐treated mice developed IgM against Dsg3 and showed intercellular IgM deposits in skin, nostrils and tongue. In contrast, in a previous study, 41% of SCID mice injected with PBL from patients with PV developed anti‐Dsg3 antibodies in vivo. Conclusions Our inability to reproduce these findings may be due to the transfer of slightly lower numbers of PBL (20 × 106 vs. 25–30 × 106).
DNA mismatch repair gene mutations in human cancer.
Authors: P Peltomäki
Journal: Environmental Health Perspectives (1997)

A new pathogenetic mechanism leading to cancer has been delineated in the past 3 years when human homologues of DNA mismatch repair (MMR) genes have been identified and shown to be involved in various types of cancer. Germline mutations of MMR genes cause susceptibility to a hereditary form of colon cancer, hereditary nonpolyposis colon cancer (HNPCC), which represents one of the most common syndromes associated with cancer predisposition in man. Tumors from HNPCC patients are hypermutable and show length variation at short tandem repeat sequences, a phenomenon referred to as microsatellite instability or replication errors. A similar abnormality is found in a proportion of sporadic tumors of the colorectum as well as a variety of other organs; acquired mutations in MMR genes or other endogenous or exogenous causes may underlie these cases. Genetic and biochemical characterization of the functions of normal and mutated MMR genes elucidates mechanisms of cancer development and provides tools for diagnostic applications.
Abstract 3144: PDZ-RhoGEF/β-arrestin-1 interaction mediates endothelin A receptor-induced RhoA activation and cell motility in ovarian tumor cells
Authors: Piera Tocci, Roberta Cianfrocca, Elisa Semprucci, Valeriana Di Castro, Anna Bagnato, Laura Rosanò
Journal: Cancer Research (2014)

Abstract β-arrestins (β-arrs), consisting of β-arr1 and β-arr2, are involved in G-protein-coupled receptor signaling, and guide the receptor signals in chemotaxis and cytoskeletal reorganization. Among them, receptor A for endothelin-1 (ET-1), namely ETAR, is overexpressed in epithelial ovarian cancer (EOC) and promote metastatic spread. We have recently reported that β-arr1 regulates ETAR-mediated β-catenin signaling to promote EOC cell invasion. Here we evaluated the effects of ET-1 on polarized cell migration correlating with the regulation of Rho-GTPase activity and its subsequent organization of the actin structures supporting migration and the involvement of β-arr1 in these effects. We show that, in EOC cells cultured on collagen type I, ET-1 promotes actin-based dynamic protrusion resembling to pseudopodia, containing β-arr-1. Furthermore, in a β-arr1/ETAR-dependent manner, ET-1 activates RhoA GTPase and downstream the dephosphorylation/activation of cofilin, as shown by pull down assay and immunoblotting analysis. The inhibitory effect of the Rho pathway inhibitor I, Y-27632, demontrates that RhoA GTPase is involved in ET-1-induced cell migration. By screening members of a Rho-guanine nucleotide exchange factor (Rho-GEF) family involved in RhoA activation, we found that PDZ-RhoGEF mRNA levels are highly expressed in EOC cells. Moreover, PDZ-RhoGEF is responsible for ET-1-induced RhoA activation through interaction with β-arr1, that in turn, promotes PDZ-RhoGEF tyrosine phosphorylation and activation. Depletion of PDZ-RhoGEF expression significantly impaired ET-1-stimulated migration of EOC cells, demonstrating that PDZ-RhoGEF/β-arrestin-1 interaction mediates ETAR-driven ovarian tumor cell motility through regulation of RhoA. Analysis of EOC human tissues revealed that PDZ-RhoGEF is overexpressed in human EOC tissues. Collectively, our data establish a novel role for β-arr1 and PDZ-RhoGEF as regulator of ET-1-induced EOC cell migration, unraveling new components required for tumor progression. Supported by AIRC. Citation Format: Piera Tocci, Roberta Cianfrocca, Elisa Semprucci, Valeriana Di Castro, Anna Bagnato, Laura Rosanò. PDZ-RhoGEF/β-arrestin-1 interaction mediates endothelin A receptor-induced RhoA activation and cell motility in ovarian tumor cells. [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 3144. doi:10.1158/1538-7445.AM2014-3144
Viscoelastic behavior of the thoracic aorta of dogs and rabbits.
Authors: B J Gentile, D R Gross
Journal: Circulation Research (1985)

Data are presented which demonstrate no correlation between atrial electrical activity and diameter changes in the descending thoracic aorta of dogs or rabbits. The experiments conducted included bypassing a segment of the descending thoracic aorta in dogs, and production of a variety of arrhythmias without the bypass in dogs and rabbits. We found no evidence of electrical stimulation-induced phasic activity as suggested by other authors.
Doctors condemn NICE's guidance on leukaemia drug
Authors: S. Mayor
Journal: BMJ (2002)

Leukaemia specialists in the United Kingdom are actively campaigning to overturn draft guidance issued by the National Institute for Clinical Excellence (NICE) that the signal transduction inhibitor imatinib (Glivec) should be used only in NHS patients with advanced chronic myeloid leukaemia.

The NICE appraisal consultation document recommends imatinib for the treatment of patients with accelerated phase chronic myeloid leukaemia (CML). However, it did not recommend its use for …
Why match in case-control studies?
Authors: P. Sedgwick
Journal: BMJ (2012)

Researchers investigated the effectiveness of a monovalent rotavirus vaccine against severe rotavirus diarrhoea in children aged under 2 years. A case-control study design was used. In total, 323 children were recruited from seven hospitals in El Salvador after admission with laboratory confirmed rotavirus diarrhoea. For each case three controls, matched for age (within 30 days of date of birth) and neighbourhood, were recruited.1

Vaccination history was confirmed after inspection of vaccination cards held by the parents. Potential risk factors—including demographics, socioeconomic factors, birth weight, premature birth, current body mass index, history of breast feeding, day care attendance and medical history—were collected from hospital records or in interviews with parents. The researchers concluded that the monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged under 2 years in El Salvador. No differences were reported between cases and controls in breastfeeding patterns, premature birth, maternal education, or …
Infections Transmitted through Musculoskeletal-Tissue Allografts
Authors: Robin Patel, Andrej Trampuz
Journal: New England Journal of Medicine (2004)

The 2003 Institute of Medicine report Microbial Threats to Health: Emergence, Detection, and Response lists “advances in medical technologies, such as blood transfusions and organ transplants,” as one reason for “new or enhanced microbial threats.” Musculoskeletal allografts represent a form of technology that poses a risk of transmission of infection, and their use is increasing. In 2002, approximately 1 million such allografts were distributed in the United States. Unlike solid-organ allografts, most musculoskeletal allografts are used for life-enhancing rather than life-saving procedures, and as the report by Kainer et al. in this issue of the Journal (pages 2564–2571) demonstrates, their . . .
EXTRACORPOREAL PLASMA THERAPY FOR HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA
Authors: B. Graisely, M. Cloarec, S. Salmon, J. Polonovski, Cl. Polonovski, J.M. Delacotte, J. Gardent, J. Cavalier, D. Vergoz, Ch. Salmon
Journal: The Lancet (1980)
Idiosyncrasy Towards Eggs.
Authors: J. Ch. Dodds
Journal: JAMA (1891)

<h3>To the Editor:</h3> —I desire to place on record the following: A lady 27 years of age, has since a child never been able to eat an egg without suffering an attack of cholera morbus (to all appearances). The same condition occurs when she eats them in any form, as cake, etc., or any method of preparing them. The lady is in all other respects normal and in good health and development. Denver, Col.
Renal transplantation in HIV-infected patients: 2010 update
Authors: Joan C. Trullas, Federico Cofan, Montse Tuset, María J. Ricart, Mercedes Brunet, Carlos Cervera, Christian Manzardo, María López-Dieguez, Federico Oppenheimer, Asuncion Moreno, Josep M. Campistol, Jose M. Miro
Journal: Kidney International (2011)
Theophylline-Induced Seizures in Adults
Authors: CLIFFORD W. ZWILLICH
Journal: Annals of Internal Medicine (1975)

Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.
P1265 UNDERSTANDING THE IMPACT OF AGE ON HEPATIC INNATE IMMUNE RESPONSES IN HEPATITIS C VIRUS PATHOGENESIS AND RESPONSE TO INTERFERON THERAPY
Authors: D.L. Hedegaard, S. Lissauer, G. Reynolds, I. Rowe, J. Sira, S. Hubscher, P. Balfe, D.A. Kelly, J.A. McKeating
Journal: Journal of Hepatology (2014)
Acute colitis in a district general hospital.
Authors: H W Jones, J Grogono, A M Hoare
Journal: BMJ (1987)

A review of all patients who had been admitted to hospital with acute ulcerative colitis in one health district between 1975 and 1984 showed that 96 had required 114 admissions with acute colitis: 42% (40) were admitted during their first attack, and 20% (19) required urgent surgery. A further nine patients underwent surgery after responding initially to intensive medical treatment that did not check the attack. There were no deaths from acute colitis. Thirteen patients underwent elective surgery for ulcerative colitis, and there were no deaths. The prognosis for acute colitis in district general hospitals has improved.
The effects of fast neutrons on inoperable carcinoma of the stomach.
Authors: M Catterall, D Kingsley, G Lawrence, J Grainger, J Spencer
Journal: Gut (1975)

Thirty-nine unselected patients suffering from inoperable, recurrent, or residual adenocarcinoma of the stomach were referred for palliation with fast neutrons from the Medical Research Council's cyclotron at Hammersmith Hospital. A full course of 1440 rads given in 12 treatments over 26 days was administered to the patients. Because of the relatively low energy (7-5 MeV) of the beam from this particular machine, it was not possible to deliver the full dose uniformly throughout the tumour except in extremely thin patients. Pain, dysphagia, vomiting, and bleeding were relieved in the majority of cases. The side effects were minimal and easily controlled. Palpable masses disappeared. Five patients required surgery after neutron therapy. All the incisions were made through irradioated tissue and all except one healed normally. Tumour was present outside the treated area, but the absence of any palpable mass within the treated area was a consistent finding. Radiologically, the stomachs remained abnormal and later changes included gross mucosal abnormality and shrinkage. Fourteen patients came to necropsy and in 10 no tumour was present macroscopocally. Tumour cells were seen in all except two cases but these were few, surrounded by dense fibrous tissue, and may not have been viable. The remaining stomach was abnormal with a thickened wall and destruction of mucosa. Three of the four cases in which macroscopic tumour was present received less than the standard dose because of the inadequate penetration of the beam. Excellent regression of tumors was achieved by the neutrons, but the stomachs did not recover from this satisfactorily. Gastrectomy four to six months after treatment is therefore suggested. This operation and other surgical procedures in other patients were successfully carried out. There is a need for higher energy neutrons to improve treatment and extend it to patients of thick-set build.
Cyclosporine for Ocular Inflammatory Diseases
Authors: R. Oktay Kaçmaz, John H. Kempen, Craig Newcomb, Ebenezer Daniel, Sapna Gangaputra, Robert B. Nussenblatt, James T. Rosenbaum, Eric B. Suhler, Jennifer E. Thorne, Douglas A. Jabs, Grace A. Levy-Clarke, C. Stephen Foster
Journal: Ophthalmology (2010)
Type 2B von Willebrand's disease in thirteen individuals from five unrelated Australian families: Phenotype and genotype correlations
Authors: D.A. Facey, E.J. Favaloro, E. Maxwell, R. Baker, M.S. Hertzberg
Journal: American Journal of Hematology (2000)

Type 2B von Willebrand's disease (VWD) is due to a qualitative defect in von Willebrand factor (VWF) in which there is an increased affinity for the platelet glycoprotein Ib-IX-V receptor complex. Spontaneous binding of type 2B VWF to platelets and subsequent clearance from the plasma is thought to account for the characteristic phenotype of type 2B VWD. These gain-of-function mutations are due to single amino substitutions that are clustered within the functionally important A1 domain of VWF. We describe 13 individuals from five unrelated families in Australia with type 2B VWD, report their phenotypic abnormalities, and delineate their causative mutations. We confirm that the mutation Arg543Trp is also particularly common among families with type 2B VWD in Australia.
PD06-04: Uptake and Economic Impact of First-Cycle Colony Stimulating Factor Use during the Adjuvant Treatment of Breast Cancer.
Authors: DL Hershman, ET Wilde, JD Wright, DL Buono, K Kalinsky, J Malin, WY Tsai, AI Neugut
Journal: Cancer Research (2011)

Abstract Background: In 2002, pegfilgrastim was approved by the FDA and the benefits of dose-dense breast cancer(BC) chemotherapy were reported. A meta-analysis revealed these benefits were limited to hormone receptor negative tumors (20% risk reduction), where hormone receptor positive cancers had a minimal 2% risk reduction. We examined first-cycle growth factor use(FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy by hormone receptor status. Methods: We identified subjects in SEER-Medicare&amp;gt;65 years oldwith stage I-III BC between 1998 and 2005who had≥1 chemotherapy claim within one year of diagnosis. We classified those with an average cycle length &amp;lt;21 days as having had dose-dense therapy. The associations of patient, tumor, and physician-related factors with receipt of any CSF and FC-CSF use were analyzed using GEE. Costs and event-free life-years saved were estimated for patients by HR status. Results: Among the 11,143 patients identified, 5,356(48.1%) hada CSF claim during therapy and 2095(18.8%) had FC-CSF. CSF use increased from 25.4% to 70.9%, FC-CSF increased from 6.4% to 46.9% and pegfilgrastim increased from 5% to 85%. During this time receipt of the combination of an anthracycline and a taxane increased from 12% to 47%. In a multivariable analysis, any CSF use was associated with age, treatment by an oncologist, and chemotherapy type; and negatively associated with black/Hispanic race, rural residence and shorter chemotherapy duration. FC-CSF use was associated also with higher SES. For hormone receptor negative patients, the cost per event-free life year saved was $5,512, with annual costs of $19.5 million. For hormone receptor positive patients, however, there was no savings in life years (and therefore no relevant cost per event-free life year saved) with annual costs of $38.8 million for those over 65. The annual costs were estimated at $86.1 million for the hormone receptor positive patient population incorporating all ages. Conclusions: Our study demonstrated a widespread increase in the use of CSF's and specifically first cycle pegfilgrastim in elderly women receiving adjuvant chemotherapy for breast cancer. This 4-fold increase came shortly after published reports of the benefits of dose-dense therapy. While this approach is very cost-effective in women with hormone receptor negative tumors, it has come at great financial cost in women with hormone receptor positive tumors who are less likely to have a meaningful benefit. In order to reduce the total costs of cancer-care, efforts should be made to ensure that these treatments are reserved for only those who benefit substantially from their use. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD06-04.
IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease
Authors: Salvatore Petta, Stefania Grimaudo, Calogero Cammà, Daniela Cabibi, Vito Di Marco, Giusalba Licata, Rosaria Maria Pipitone, Antonio Craxì
Journal: Journal of Hepatology (2012)
Advances in Clinical Obstetrics and Gynecology
Authors: Dave E. David
Journal: JAMA (1982)

There is no specialty of medicine more replete with socially and medically controversial topics than obstetrics and gynecology. Additionally, it is one of the most rapidly advancing fields, particularly in the subspecialties of endocrinology and perinatology. Dr Osofsky's keenly edited 19-chapter compilation offers the reader a fine update on the advances in our field. It recapitulates the state of the art and standards of management of various obstetric and gynecologic problems today. No longer is it necessary to search laboriously through journals for the latest on fetal monitoring interpretation, laser therapy, or the use of antenatal steroids or tocolytic agents. The references at the end of each chapter are refreshingly recent. The social aspects of obstetrics and gynecology are adequately dealt with in chapters on abortion-related Supreme Court decisions, cesarean section rates, and medicolegal issues. It is reassuring to read updates by such leaders (in their respective fields) as Mishell,