tbuckley/cabot-search huggingface dataset:
Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation.
Authors: C Zeidler, K Welte, Y Barak, F Barriga, A A Bolyard, L Boxer, Guy Cornu, M J Cowan, D C Dale, T Flood, M Freedman, H. Gadner, H. Mandel, R J O'Reilly, U Ramenghi, A Reiter, R Skinner, Christiane Vermylen, J E Levine
Journal: Blood (2000)
More than two years of a monographic consultation on control of chronic home oxygen therapy
Authors: Teresa Bilbao Goyoaga, Natividad Quilez, Lorena Comeche, Dolores Alvaro, Juan Manuel Diez, Raquel Perez
Journal: European Respiratory Journal (2011)

Objectives: To know the characteristics of our patients on chronic home oxygen therapy. We assess the prescription criterion, the prescriber department, time since chronic home oxygen therapy started and the main diagnosis that causes the home oxygen therapy.

Materials and methods: Retrospective descriptive analysis of the patients that attend to our monographic consultation since it started on October of 2008.

Results: The number of patients is 598 with 1181 number of consultations, this means 1,9 consultations per patient. The main diagnoses frequency is COPD 558 (47,2%), Heart Disease 65 (55%), prescription criteria was adequate in most patients, the prescriber was Pulmonology in a 31,8%. From the 598 patients evaluated were prescribed to105 cease prescription, representing a 17.5% after a mean of 469 days (15.4 months). The most common diagnoses in such patients were: COPD 43 (40%), Heart disease20 (19%),. The diagnostic groups that less time in oxygen therapy required were Respiratory Infection 67 days. The diagnostic groups to which therapy were withdrawn most frequently were: Pneumonia 28%, Heart Disease 23%,

Conclusions: Most patients who come to the consultation have a diagnosis of COPD and are referred primarily from the Pulmonology department with a correct prescription criteria. The withdrawal of OCD is made after an average time in therapy of 15 months. This cease of prescription is made in 8,9% of the consultations representing 17,5% of the total number or patients. The most frequent diagnoses on these patients not differ from those pursuing therapy but oxygen therapy was withdrawn more frequently in pathologies potentially reversible and those also needed less time.
Poor efficacy of nucleic acid testing in identifying occult HBV infection and consequences for safety of blood supply in Italy
Authors: Marta Spreafico, Alessandra Berzuini, Barbara Foglieni, Daniel Candotti, Livia Raffaele, Irene Guarnori, Agostino Colli, Francesco Fumagalli Maldini, Jean-Pierre Allain, Daniele Prati
Journal: Journal of Hepatology (2015)
India records large rise in malaria cases in 2014
Authors: C. Travasso
Journal: BMJ (2015)

The number of malaria cases in India last year rose to 1 070 513, up from 881 730 in 2013, provisional figures have shown.1 The 2014 prevalence is similar to that seen in 2012, when 1 067 824 cases were recorded. The states of Tripura and Odisha saw the largest increases, with rises of 540% and 70%, respectively.

AC Dhariwal, director of the National Vector Borne Disease Control Programme, said that the malaria outbreak in Tripura in 2014, which saw cases rise …
Abstract 15712: MiR-34 Cluster Regulates p21 mediated Cardiac Fibroblast Differentiation by Targeting Sirt-1
Authors: Sashwati Roy, Savita Khanna, Chandan K Sen
Journal: Circulation (2011)

Background. We provided first evidence documenting changes in MicroRNAs (miRNAs) expression following myocardial IR in vivo microRNA. (miR)-34 cluster function as direct and conserved p53 target ge...
Radiation therapy for malignant phyllodes tumors: An analysis of over 3,100 patients from 1998 to 2009.
Authors: Richelle T. Williams, Jennifer Lynn Gnerlich, Katharine Yao, Nora T. Jaskowiak, Swati Kulkarni
Journal: Journal of Clinical Oncology (2012)

183 Background: Malignant phyllodes tumors of the breast are uncommon. Currently, there are no standard treatment guidelines for adjuvant therapy. We hypothesized that there has been a trend towards increased use of radiation despite its uncertain effect on outcomes. Methods: Using the National Cancer Data Base, treatment trends and predictors of radiation utilization were examined for women with malignant phyllodes from 1998 to 2009. Kaplan-Meier and Cox regression were used to determine the effect of radiation on local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Results: Of 3,153 patients, 57.4% underwent lumpectomy and 42.6% underwent mastectomy. Overall, 14.2% received radiation, with utilization doubling over the study period (9.2% in 1998 vs. 19.8% in 2009, p&lt;0.001). Women were significantly more likely to receive radiation if they were diagnosed later in the study (OR 2.25, 95% CI 1.26-4.03), were age 50-59 (OR 1.64, 95% CI 1.13-2.39), had tumors &gt;10cm (OR 2.28, 95% CI 1.55-3.35), or had nodes removed (OR 2.04, 95% CI 1.56-2.69). Race/ethnicity, socioeconomic factors, hospital characteristics, type of surgery, and margin status were not independent predictors of radiation. Of 1,758 patients with known recurrence status, overall recurrence was 13.8% and LR was 5.9%. With 50 months median follow-up and controlling for potential confounders, radiation reduced LR (aHR 0.41, 95% CI 0.18-0.92) but had no impact on DFS or OS. Conclusions: Use of adjuvant radiation for malignant phyllodes doubled from 1998 to 2009. Tumor factors and time were the main determinants of utilization. Radiation decreased LR but had no effect on DFS or OS.
Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia
Authors: P Wright, P T Donaldson, J A Underhill, K Choudhuri, D G Doherty, R M Murray
Journal: American Journal of Psychiatry (1996)

The authors investigated the human leukocyte antigen (HLA) DRB1*04 gene in schizophrenic patients because it is positively associated with rheumatoid arthritis, an autoimmune disease that exhibits a strong negative association with schizophrenia. The HLA DQB1*0602 allele was also studied because of previous reports of genetic association between it and schizophrenia. Maternal HLA was investigated because of the reported association between prenatal influenza and schizophrenia and the central role of HLA molecules in the immune response to viral infections.Polymerase chain reactions and sequence-specific oligonucleotide probes were used to genotype 94 unrelated patients with DSM-III-R schizophrenia, 92 mothers of schizophrenic offspring who were not related either to each other or to the 94 patients, and 177 healthy comparison subjects.The frequency of DRB1*04 alleles was significantly lower in both the schizophrenic patients and the unrelated mothers of schizophrenic offspring than in the healthy comparison subjects. No significant differences were found for DQB1*0602.DRB1*04 alleles may partially account for the genetic predisposition to schizophrenia. The association reported here may be explained by genetic linkage or by an autoimmune pathophysiology for a proportion of schizophrenia cases. Alternatively, it may be that maternal B lymphocytes that do not express the DR4 antigen encoded by DRB1*04 respond to influenza virus by producing antibodies that perturb neurodevelopment, thus underpinning a proportion of schizophrenia cases.
Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report.
Authors: M Hussain, M Wolf, E Marshall, E D Crawford, M Eisenberger
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the impact of prognostic factors, including continued (orchiectomy) versus discontinued androgen-suppression (nonorchiectomy) therapy, on chemotherapy response and survival of patients with hormone-refractory prostate cancer. METHODS Analysis of five consecutive Southwest Oncology Group (SWOG) phase II chemotherapy trials was undertaken. RESULTS Two hundred five hormone-refractory patients were evaluated. Eighty-four percent had been orchiectomized. The median survival durations for the nonorchiectomy and orchiectomy patients were 6 and 7 months, respectively (P = .73). In a univariate analysis, orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy (1.1 v 0.1 years, P = .003), were more likely to have had chemotherapy initiated &gt; or = 2 years from diagnosis (75% v 56%, P = .03), had a lower incidence of liver metastases (16% v 30%, P = .05), and had lower likelihood of being black (8% v 18%, P = .05) when compared with the nonorchiectomy group. Orchiectomy patients had a marginally significant longer median time from initial hormone treatment, more prior endocrine manipulations, lower median baseline alkaline phosphatase levels, and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group. Absence of liver metastases (P = .004), hemoglobin level &gt; or = 10 g/dL (P &lt; .001), acid phosphatase level &gt; or = 1.2 IU/L (P = .05), response to chemotherapy (P = .001), and &gt; or = 2 years from initial hormone treatment (P = .01) are important factors for survival. CONCLUSION This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression. A prospective randomized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy.
Comparison of Breast Magnetic Resonance Imaging, Mammography, and Ultrasound for Surveillance of Women at High Risk for Hereditary Breast Cancer
Authors: E. Warner, D. B. Plewes, R. S. Shumak, G. C. Catzavelos, L. S. Di Prospero, M. J. Yaffe, V. Goel, E. Ramsay, P. L. Chart, D. E.C. Cole, G. A. Taylor, M. Cutrara, T. H. Samuels, J. P. Murphy, J. M. Murphy, S. A. Narod
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Recommended surveillance for BRCA1 and BRCA2 mutation carriers includes regular mammography and clinical breast examination, although the effectiveness of these screening techniques in mutation carriers has not been established. The purpose of the present study was to compare breast magnetic resonance imaging (MRI) with ultrasound, mammography, and physical examination in women at high risk for hereditary breast cancer. PATIENTS AND METHODS: A total of 196 women, aged 26 to 59 years, with proven BRCA1 or BRCA2 mutations or strong family histories of breast or ovarian cancer underwent mammography, ultrasound, MRI, and clinical breast examination on a single day. A biopsy was performed when any of the four investigations was judged to be suspicious for malignancy. RESULTS: Six invasive breast cancers and one noninvasive breast cancer were detected among the 196 high-risk women. Five of the invasive cancers occurred in mutation carriers, and the sixth occurred in a woman with a previous history of breast cancer. The prevalence of invasive or noninvasive breast cancer in the 96 mutation carriers was 6.2%. All six invasive cancers were detected by MRI, all were 1.0 cm or less in diameter, and all were node-negative. In contrast, only three invasive cancers were detected by ultrasound, two by mammography, and two by physical examination. The addition of MRI to the more commonly available triad of mammography, ultrasound, and breast examination identified two additional invasive breast cancers that would otherwise have been missed. CONCLUSION: Breast MRI may be superior to mammography and ultrasound for the screening of women at high risk for hereditary breast cancer.
Selective IgA deficiency and the risk of asthma
Authors: Camilla Celani, Anna Maria Zicari, Valeria Lollobrigida, Azzurra Cesoni Marcelli, Maria Palma Carbone, Valentina De Vittori, Marzia Duse
Journal: European Respiratory Journal (2013)

Introduction:Selective IgA deficiency (IgAD), the most frequent primary immunodeficiency is associated with a wide variety of clinical manifestations including an increased frequency of allergic manifestations such us asthma.  Objective: To describe the prevalence of allergies and asthma in a selected population of children with IgAD.  Materials and Methods: We included 27 children(15 males)with a diagnosis of IgA deficiency with a mean age of onset of symptoms 37.58 ± 29 months. Each subject was investigate about clinical presentation at the time of the diagnosis and allergic skin tests for food allergens and inhalants were performed.  Results: At the beginning children with IgAD presented principally infections of the upper and lower airways, 5/27(18,5%)had pneumonia.16/27(59,3%) had Prick test positivity with associated allergic diseases. Among the allergens house dust mites were the most frequent (22,2%) followed by grass pollens(11,1%).7/27(25,9%) presented asthma symptoms and 6/27(22%) rhinoconjunctivitis and atopic eczema. The prevalence of asthma symptoms is more higher in our population of children with IgAD respect to the general pediatric population, respectively 25.9 vs 7.9 (Tozzi AE Pediatric Allergy Immunol 2011) and the difference is statistically significant (p  Conclusions: Children with selective IgA deficiency seem to have an increased risk of having recurrent infections and allergic manifestations respect to general pediatric population. Observations that IgAD is associated with an increased prevalence of atopy suggest a possible role of IgA in asthma pathogenesis. The mucosal antigen exposure seems to be increased in the absence of IgA, causing an increased production of IgE against allergens.
Medication in Police Custody
Authors: A Busuttil, N W Wallace
Journal: Journal of the Royal Society of Medicine (1990)

Police Officers have an obligation to look after the welfare of the persons detained by them. As such persons may require to be given medication on a regular basis during their period of custody which may last a few days, the Police are also responsible for ensuring that this takes place. To identify the extent of this requirement, a survey was carried out by questionnaire in Edinburgh over a period of one month. Thirty-five per cent [corrected] of the 127 detainees were carrying with them a variety of drugs or required to be given medication on a regular basis. The problems associated with this practice are discussed.
Quality of Life Measurements in Eating Disorders, Angina, and Transplant Candidates: Are They Comparable?
Authors: Matthias Keilen, Tom Treasure, Ulrike Schmidt, Janet Treasure
Journal: Journal of the Royal Society of Medicine (1994)

The measurement of health-related quality of life has attracted much attention and is now a component of most big clinical trials. As we evaluate and choose between treatments and make judgements about priorities in health care, it is important that the equivalent data are available for different patient groups.
Abstract 1439: Cytochrome P450 Genetic Variants Predict Cardiovascular Outcomes following Treatment with Clopidogrel but not with Prasugrel
Authors: Jessica L Mega, Lei Shen, Stephen D Wiviott, Joseph R Walker, Richard D Hockett, John T Brandt, Brian A Moser, William Macias, Elliott M Antman, Sandra L Close, Eli Lilly, Marc S Sabatine
Journal: Circulation (2008)

Background : Prasugrel and clopidogrel require transformation into active metabolites by cytochrome P450 (CYP) enzymes. Variants in CYP genes, particularly CYP2C19 , are associated w/ reduced levels of metabolite and platelet inhibition w/ clopidogrel but not prasugrel. We investigated the impact of variants in CYP genes on clinical outcomes. Methods : TRITON-TIMI 38 randomized ACS patients w/ planned PCI to prasugrel (60 mg load, 10 mg qd) or clopidogrel (300 mg, 75 mg qd) for 6–15 mos. DNA was available in 2943 subjects who were genotyped for functional polymorphisms in CYP2C19 , 2C9 , 3A4/5 , 2B6 , and 1A2 and classified for each gene as carriers or non-carriers of ≥1 reduced function allele. Results : Among subjects treated with clopidogrel, CYP2C19 reduced function allele carriers (27% of population) had a 53% increased risk of the primary efficacy endpoint of CV death, MI, or stroke (HR 1.53, P=0.007, Fig ) and a 3-fold increased risk of ARC-defined definite or probable stent thrombosis (HR 3.09, P=0.038) compared w/ non-carriers. In contrast, with prasugrel CYP2C19 reduced function allele carriers were not at increased risk of CV death, MI, or stroke (HR 0.89, P=0.86) or stent thrombosis (HR 0.60, P=0.57). No association between genotype and bleeding was observed w/ either treatment. There were no statistically significant associations between any other tested CYP genotypes and outcomes. Conclusions : CYP2C19 genetic variants identify patients at significantly higher risk for CV death, MI, or stroke and for stent thrombosis among those treated with clopidogrel but not among those treated with prasugrel. CYP2C19 genotyping offers the potential to help tailor antiplatelet therapy.
Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer.
Authors: F Cavalli, A Goldhirsch, F Jungi, G Martz, None MermillodB, P Alberto
Journal: Journal of Clinical Oncology (1984)

In a randomized trial, 210 postmenopausal women with advanced measurable breast cancer were allocated to two different schedules of medroxyprogesterone acetate (MPA). In the induction phase they received either 1,000 mg intramuscular (IM) MPA (high dose) daily or 500 mg IM MPA (low dose) twice weekly for four weeks. The maintenance treatment consisted of 500 mg MPA IM once weekly for all patients. In total, 184 patients were considered evaluable. The response rate was significantly higher (p = 0.004) for patients receiving high-dose MPA (30 [33%] of 91) as compared to the women receiving the low-dose regimen (14 [15%] of 93) and was consistent across all prognostic subgroups. These prognostic subgroups included soft-tissue and osseous metastases, two metastatic sites, patients greater than 60 years, disease-free interval greater than 60 months, no prior chemotherapy, patients with a response to the last hormonal treatment before MPA, unknown estrogen receptors, and positive progestin receptors. The two different schedules of MPA did not influence the time to progression and the survival. Toxicity was similar in both regimens. These results confirm that a higher response rate can be achieved with a more intensive MPA schedule. This treatment may represent an ideal second-line choice in the endocrine therapy of advanced breast cancer; however, its role as a first-line treatment remains to be defined.
Studies on the prekallikrein (kallikreinogen)-kallikrein enzyme system of human plasma
Authors: Robert W. Colman, Lawrence Mattler, Sol Sherry
Journal: Journal of Clinical Investigation (1969)

By measurement of its arginine esterase activity, plasma kallikrein was purified from fresh frozen ACD plasma. The steps involved alcohol fractionation, isoelectric precipitation, and carboxymethyl (CM) Sephadex and DEAE cellulose chromatography. Three enzymatically active fractions were finally isolated and termed plasma kallikreins I, II, and III; they represented purifications of 970,320- and 590-fold, respectively. All three kallikreins were active biologically; they increased vascular permeability in the guinea pig and released a kinin from human plasma, as measured in the rat uterus bioassay. Bradykinin and/or closely related kinins were identified in the kallikrein I plasma digest by radioimmunoassay. Kallikreins I, II, and III had similar ratios of hydrolytic activity on a variety of arginine and lysine esters and were immunochemically related. However, differences were present on physicochemical characterization: kallikrein I had S(20,[unk]) of 5.7, a mol wt of 99,800, and migrated as a slow gamma globulin; kallikrein II migrated as a fast gamma globulin with a mol wt of 163,000, but the evidence suggested that it was closely related, if not interconvertible, with kallikrein I. Kallikrein III, on the other hand, migrated as an alpha globulin and reacted quite differently with inhibitors.
shRNAs significantly reduce the replication of RSV in vitro
Authors: Musa Khaitov, Igor Shilovsky, Dmitriy Mazurov, Evgeniy Faizuloev
Journal: European Respiratory Journal (2011)

Background:  RNA interference (RNAi) is a powerful tool to silence gene expression on the level of mRNA. To knock-down gene expression by using RNAi two major methods of mRNA silencing exist. First method utilizes siRNA (small interfering RNA), a readily processed dsRNA, that enters RISC complex and destroy target mRNA after transfection into the cells. The second method based on the construction of plasmid DNA that expresses shRNA (short harpin RNA) from U6 or CMV promoter. shRNA gets processed by Drosha and Dicer RNAses inside the cell before it translocates to the cell cytoplasm and affects the level of target RNA. In this study we investigated the ability of specific vector constructs coding shRNA molecules to target the expression of respiratory syncytial virus (RSV) phosphoprotein P in vitro and thus inhibit the replication of RSV.   Methods:  Lentiviral vector pGIPZ expressing tGFP-IRES-Puro-shRNAmir30 cassette was modified by introducing BamH I restriction site downstream of this cassette. This modification makes possible to clone specific shRNA sequences in pGIPZ vector using XhoI/BamHI restriction sites instead of the original recombination.   Results:  Three shRNAs against phosphoprotein P RSV and shRNA against human CD43 as a control were generated and cloned into modified so-called pGIPD vector. Monkey kidney cells MA-104 were stably transduced with four shRNA constructs. MA-104 cells transduced with shRNA constructs against RSV P protein demonstrated significant inhibition of of RSV replication after the infection than compared to the control and not transduced cells.   Conclusion:  The generated constructs can be successfully used for efficient gene silencing and virus replication inhibition in vitro.
Phase I study of RAD001 (everolimus), cetuximab, and irinotecan as second-line therapy in metastatic colorectal cancer (mCRC)
Authors: S. Sharma, T. Reid, S. Hoosen, C. Garrett, J. Beck, S. Davidson, M. MacKenzie, U. Brandt, J. Hecht
Journal: Journal of Clinical Oncology (2009)

e15115 Background: The PI3K/AKT/mTOR pathway is frequently dysregulated in colorectal cancer (Cancer Res 2005;65:11227). In a phase I study in patients with advanced solid tumors, everolimus an oral mTOR inhibitor demonstrated clinical benefit including a partial response in pts with colorectal cancer (J Clin Oncol 2008;26:1603–10; J Clin Oncol 2008; 26:1588–95). Methods: This open-label, multicenter phase I study uses a Bayesian logistic model to identify feasible doses of everolimus + irinotecan + cetuximab. Adult pts with mCRC progressing despite prior 5-FU/oxaliplatin (FOLFOX) or capecitabine/oxaliplatin (XELOX) plus bevacizumab (if standard practice) were treated using a sequential dose escalation scheme (Table). Dose decisions were driven by the probability of dose-limiting toxicity (DLT) in the first 2 cycles. Dose level decisions were based on maximizing the probability that end-of-cycle-2 DLT rate would be within the targeted toxicity interval (20% to &lt;35%) and minimizing the risk of over-dosing (&lt; 5% risk of unacceptable toxicity and &lt; 25% risk of excessive/unacceptable toxicity). Results: 18 pts were treated from April ‘07 to August ‘08, 5 pts at dose level A1 and 13 pts at dose level B1. Two DLTs (G3 rash on cycle 2 day 1 lasting &gt; 7 days and G3 mucositis on cycle 1 day 14 lasting &gt; 7 days, 1 pt each) were reported in 4 evaluable pts at dose level A1. No DLTs were reported in 7 evaluable patients at dose level B1. Conclusions: At dose level B1 everolimus in combination with irinotecan and cetuximab was generally well tolerated. The study was stopped due to changes in clinical practice based on emerging data indicating that cetuximab has limited efficacy in mCRC patients with KRAS mutations and that efficacy data favors daily RAD001 over weekly dosing. Patients in this study were treated with cetuximab irrespective of KRAS status. [Table: see text] [Table: see text]