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2.
Ir Med J ; 115(2): 546, 2022 02 17.
Article En | MEDLINE | ID: mdl-35420007

Presentation A 24-year-old newly graduated junior doctor presented to the emergency department with acute onset chest pain, haemoptysis and exertional dyspnoea following a dry needling session. Diagnosis Chest x-ray showed bilateral pneumothoraces, worse on the right side. Treatment The bilateral pneumothoraces were treated conservatively with supplemental oxygen initially. On the second day of admission, repeat chest x-ray demonstrated a worsening right sided pneumothorax. While vitally stable, the patient however had become increasingly dyspnoeic, and a needle aspiration was performed on the right side with good effect. Conclusion The anatomical location targeted along with the patients low-normal BMI makes her high-risk when considering the skin-to-pleura distance. Although the incidence of pneumothorax is low, it is imperative that we improve awareness both for the treating physician and the diagnosing clinician. We must begin to fill the distinct lack in available literature surrounding the potential adverse effects of dry needling.


Acupuncture Therapy , Dry Needling , Pneumothorax , Acupuncture Therapy/adverse effects , Adult , Chest Pain/etiology , Dyspnea/etiology , Dyspnea/therapy , Female , Humans , Pneumothorax/diagnostic imaging , Pneumothorax/etiology , Pneumothorax/therapy , Young Adult
3.
BJOG ; 127(12): 1548-1556, 2020 11.
Article En | MEDLINE | ID: mdl-32633022

OBJECTIVE: To describe differences in outcomes between pregnant women with and without coronavirus dsease 2019 (COVID-19). DESIGN: Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription-polymerase chain reaction. All infants of mothers with COVID-19 underwent SARS-CoV-2 testing. SETTING: Three New York City hospitals. POPULATION: Pregnant women >20 weeks of gestation admitted for delivery. METHODS: Data were stratified by SARS-CoV-2 result and symptomatic status, and were summarised using parametric and nonparametric tests. MAIN OUTCOME MEASURES: Prevalence and outcomes of maternal COVID-19, obstetric outcomes, neonatal SARS-CoV-2, placental pathology. RESULTS: Of 675 women admitted for delivery, 10.4% were positive for SARS-CoV-2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities among women with symptomatic COVID-10 versus asymptomatic COVID-19 versus no COVID-19. Caesarean delivery rates were 46.7% in symptomatic COVID-19, 45.5% in asymptomatic COVID-19 and 30.9% in women without COVID-19 (P = 0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID-19 versus 4.5% of women without COVID-19 (P < 0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS-CoV-2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with COVID-19 versus women without COVID-19 (48.3% versus 11.3%, P < 0.001). CONCLUSION: Among pregnant women with COVID-19 at delivery, we observed increased caesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID-19 remote from delivery. TWEETABLE ABSTRACT: COVID-19 at delivery: more caesarean deliveries, postpartum complications and intraplacental thrombi.


Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Adult , COVID-19 , COVID-19 Testing , Case-Control Studies , Cesarean Section , Cohort Studies , Coronavirus Infections/complications , Female , Hospitalization , Humans , Infant, Newborn , Male , New York City , Pandemics , Pneumonia, Viral/complications , Pregnancy , SARS-CoV-2
4.
Sci Rep ; 7(1): 13788, 2017 10 23.
Article En | MEDLINE | ID: mdl-29062098

Cu(In,Ga)Se2 (CIGS) is presently the most efficient thin-film photovoltaic technology with efficiencies exceeding 22%. An important factor impacting the efficiency is metastability, where material changes occur over timescales of up to weeks during light exposure. A previously proposed (V Se -V Cu ) divacancy model presents a widely accepted explanation. We present experimental evidence for the optically induced metastability transition and expand the divacancy model with first-principles calculations. Using photoluminescence excitation spectroscopy, we identify a sub-bandgap optical transition that severely deteriorates the carrier lifetime. This is in accordance with the expanded divacancy model, which predicts that states below the conduction band are responsible for the metastability change. We determine the density-capture cross-section product of the induced lifetime-limiting states and evaluate their impact on device performance. The experimental and theoretical findings presented can allow assessment of metastability characteristics of leading thin-film photovoltaic technologies.

5.
Psychoneuroendocrinology ; 82: 164-172, 2017 Aug.
Article En | MEDLINE | ID: mdl-28550793

Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition.


Extinction, Psychological/drug effects , Leuprolide/pharmacology , Memory/drug effects , Amygdala/metabolism , Animals , Brain/metabolism , Cerebral Cortex/metabolism , Conditioning, Classical/physiology , Conditioning, Psychological/drug effects , Extinction, Psychological/physiology , Fear/physiology , Gonadotropin-Releasing Hormone/metabolism , Hypothalamo-Hypophyseal System , Leuprolide/metabolism , Male , Memory/physiology , Neurons/metabolism , Pituitary-Adrenal System/metabolism , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-Dawley , Receptors, LHRH/agonists , Receptors, LHRH/therapeutic use , Testosterone/blood
6.
Rev Sci Instrum ; 86(1): 013907, 2015 Jan.
Article En | MEDLINE | ID: mdl-25638097

Fiber-fed time-resolved photoluminescence is demonstrated as a tool for immediate process feedback after deposition of the absorber layer for CuInxGa(1-x)Se2 and Cu2ZnSnSe4 photovoltaic devices. The technique uses a simplified configuration compared to typical laboratory time-resolved photoluminescence in the delivery of the exciting beam, signal collection, and electronic components. Correlation of instrument output with completed device efficiency is demonstrated over a large sample set. The extraction of the instrument figure of merit, depending on both the initial luminescence intensity and its time decay, is explained and justified. Limitations in the prediction of device efficiency by this method, including surface effect, are demonstrated and discussed.

7.
Br J Cancer ; 109(8): 2131-41, 2013 Oct 15.
Article En | MEDLINE | ID: mdl-24052043

BACKGROUND: Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer. METHODS: The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background. RESULTS: EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102. CONCLUSION: EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.


ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Prostatic Neoplasms/drug therapy , Sulfonamides/pharmacology , Toluidines/pharmacology , ATP Binding Cassette Transporter, Subfamily B , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Docetaxel , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Drug Synergism , Humans , Male , Mice , Microtubules/drug effects , Microtubules/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Random Allocation , Sulfonamides/administration & dosage , Taxoids/administration & dosage , Toluidines/administration & dosage , Tubulin/metabolism , Xenograft Model Antitumor Assays
8.
Oncogene ; 32(35): 4139-47, 2013 Aug 29.
Article En | MEDLINE | ID: mdl-22986525

The miR-106b-25 microRNA (miRNA) cluster is a candidate oncogene in human prostate cancer. Here, we report that miRNAs encoded by miR-106b-25 are upregulated in both primary tumors and distant metastasis. Moreover, increased tumor miR-106b expression was associated with disease recurrence and the combination of high miR-106b and low CASP7 (caspase-7) expressions in primary tumors was an independent predictor of early disease recurrence (adjusted hazard ratio=4.1; 95% confidence interval: 1.6-12.3). To identify yet unknown oncogenic functions of miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that CASP7 is a direct target of miR-106b, which was confirmed by western blot analysis and a 3'-untranslated region reporter assay. Moreover, selected phenotypes induced by miR-106b knockdown in DU145 human prostate cancer cells did not develop when both miR-106b and CASP7 expression were inhibited. Further analyses showed that CASP7 is downregulated in primary prostate tumors and metastatic lesions across multiple data sets and is by itself associated with disease recurrence and disease-specific survival. Using bioinformatics, we also observed that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally examined using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and disease outcome and may do so by altering apoptosis- and focal adhesion-related pathways.


Caspase 7/genetics , Focal Adhesions , Gene Expression Regulation, Neoplastic , MicroRNAs/physiology , Neoplasm Recurrence, Local/etiology , Prostatic Neoplasms/genetics , 3' Untranslated Regions , Cell Line, Tumor , Extracellular Matrix/metabolism , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms/etiology , Prostatic Neoplasms/pathology
9.
Clin Exp Allergy ; 42(7): 1028-39, 2012 Jul.
Article En | MEDLINE | ID: mdl-22702502

BACKGROUND: Acid-sensing ion channels (ASIC) are a family of acid-activated ligand-gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR. OBJECTIVES: The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects. METHODS: Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function. RESULTS: Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre-treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC-1 was equally expressed in both populations, but ASIC-3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC-3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air-surface liquid depth via an ASIC-dependent chloride secretory pathway. CONCLUSIONS: This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC-3 expression.


Eosinophil Peroxidase/metabolism , Epithelial Cells/metabolism , Gene Expression Regulation , MAP Kinase Signaling System , Nasal Mucosa/metabolism , Rhinitis, Allergic, Seasonal/metabolism , Sodium Channels/biosynthesis , Acid Sensing Ion Channels , Adolescent , Adult , Biopsy , Cells, Cultured , Epithelial Cells/pathology , Female , Humans , Lactic Acid/pharmacology , Male , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Nasal Mucosa/pathology , Polymerase Chain Reaction , Rhinitis, Allergic, Seasonal/pathology
10.
Ir J Med Sci ; 181(1): 37-41, 2012 Mar.
Article En | MEDLINE | ID: mdl-22038747

BACKGROUND: Anti-social behaviour affects staff physically and psychologically and has financial implications. More information on its occurrence is required for effective risk management. AIMS: We undertook to audit the complete dataset on anti-social behaviour in an urban Irish hospital. METHODS: Data, collected from computerised incident reports between January 2005 and December 2008, were analysed with respect to date, location, incident type, person affected, type and severity of injury. RESULTS: There were 3,727 incidents over 4 years, with numbers rising annually at the approximate rate of 20%. Most involved nursing staff. Incidents occurred primarily on medical and surgical wards and were usually classified as minor. Physical or verbal assaults were most frequently reported. CONCLUSION: Anti-social behaviour appears to be increasing. Certain wards and categories of healthcare professionals are at particular risk. More research is required to explain factors leading to such behaviour and optimum strategies for its active management.


Aggression/psychology , Hospitals, Teaching/statistics & numerical data , Violence/psychology , Humans , Ireland , Patients/psychology , Patients/statistics & numerical data , Personnel, Hospital/psychology , Personnel, Hospital/statistics & numerical data , Theft/statistics & numerical data , Violence/statistics & numerical data , Visitors to Patients/psychology , Visitors to Patients/statistics & numerical data
11.
Ir J Med Sci ; 178(4): 433-9, 2009 Dec.
Article En | MEDLINE | ID: mdl-19437091

OBJECTIVES: To assess the safety culture in an acute medical admissions unit (AMAU) of a teaching hospital in order to benchmark results against international data and guide a unit-based, integrated, risk management strategy. METHODS: The safety attitudes questionnaire (SAQ), a validated instrument for the measurement of safety culture was applied to an AMAU. All AMAU healthcare staff (n = 92) were surveyed: doctors, nurses, healthcare assistants (HCAs) and allied healthcare professionals (AHPs). Safety attitude scores for the overall unit and individual caregiver types were assessed across six domains of safety culture. RESULTS: When compared against an international benchmark, the AMAU scored significantly higher for four of the six safety domains: p < 0.01 for 'teamwork climate', 'safety climate' and 'stress recognition' and p < 0.05 for 'job satisfaction'. The difference between nurse manager scores and the overall mean for the study group was statistically significant for the domains of 'teamwork climate' (p < 0.05) and 'safety climate' (p < 0.01). HCAs scored significantly lower relative to staff overall with regard to 'working conditions' (p < 0.05) and 'perceptions of management' (p < 0.01). CONCLUSIONS: The SAQ was successfully applied to an AMAU setting giving a valuable insight into staff issues of concern across the safety spectrum: employee and environmental safety, clinical risk management and medication safety.


Attitude of Health Personnel , Hospital Units/organization & administration , Organizational Culture , Patient Admission , Personnel, Hospital/psychology , Safety/standards , Benchmarking , Hospital Units/standards , Hospitals, Teaching , Humans , Patient Admission/standards , Surveys and Questionnaires
12.
Anticancer Res ; 27(3A): 1309-17, 2007.
Article En | MEDLINE | ID: mdl-17593624

BACKGROUND: Selection of the human drug sensitive and invasive cell line (MDA-MB-435S-F) with the chemotherapeutic agent paclitaxel, resulted in the development of drug resistant cell lines displaying enhanced invasion-related characteristics. MATERIALS AND METHODS: Serum-free conditioned media from the human cancer drug-sensitive and invasive cell line (MDA-MB-435S-F) and its paclitaxel-resistant superinvasive variant (MDA-MB-435S-F/Taxol10p4pSI) were analyzed using Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). RESULTS: A differentially expressed protein was observed at 7.6 kDa, which was 4-fold up-regulated in MDA-MB-435S-F/Taxol10p4pSI. The differentially expressed protein was identified using matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS), as a fragment of bovine transferrin. The transferrin receptor was also found to be overexpressed in the superinvasive cell line. CONCLUSION: Cleavage of serum proteins such as transferrin could provide a valuable source of markers for malignant tumours and could also play a role in aspects of cancer pathogenesis, such as tumour cachexia.


Biomarkers, Tumor/isolation & purification , Breast Neoplasms/chemistry , Neoplasm Proteins/isolation & purification , Peptide Fragments/isolation & purification , Transferrin/isolation & purification , Adult , Biomarkers, Tumor/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Culture Media, Conditioned , Drug Resistance, Neoplasm , Female , Humans , Neoplasm Invasiveness , Neoplasm Proteins/chemistry , Paclitaxel/pharmacology , Peptide Fragments/chemistry , Receptors, Transferrin/biosynthesis , Receptors, Transferrin/chemistry , Receptors, Transferrin/isolation & purification , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Transferrin/chemistry
13.
Transfusion ; 45(7): 1073-83, 2005 Jul.
Article En | MEDLINE | ID: mdl-15987350

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.


Blood Banks , Blood Donors , Hospitals , Transfusion Reaction , Virus Diseases/blood , Virus Diseases/transmission , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/transmission , HTLV-I Infections/blood , HTLV-I Infections/transmission , HTLV-II Infections/blood , HTLV-II Infections/transmission , Hepatitis, Viral, Human/blood , Hepatitis, Viral, Human/transmission , Humans , Prevalence , Transplantation, Homologous , United States , Virus Diseases/epidemiology
14.
Transfusion ; 45(7): 1089-96, 2005 Jul.
Article En | MEDLINE | ID: mdl-15987352

BACKGROUND: Calculation of viral residual risk is dependent on estimating incidence, which is not easily obtainable by most blood centers. Prevalence, however, is readily available. Understanding whether prevalence reflects corresponding incidence may help blood centers monitor disease risks. STUDY DESIGN AND METHODS: With data on 12 million allogeneic donations, prevalence and incidence of transfusion-transmitted viral infections (TTVIs) were calculated. Relationships between prevalence (in total, first-time, and repeat donations) and incidence were analyzed for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) relative to temporal and donor demographic stratifications, respectively. RESULTS: Overall prevalence of HIV, HBV, and HCV did not consistently reflect corresponding incidence. The relationship between prevalence and incidence varied with time and donors' age and was virus-specific. CONCLUSION: Incidence of TTVIs cannot be easily predicted from overall prevalence. Accurate assessment of TTVI risk necessitates knowledge about donation histories and person-years at risk. Establishing comprehensive frameworks for monitoring blood donations and infectious disease markers remains a key to monitoring blood safety.


Blood Donors , Blood Transfusion , Virus Diseases/epidemiology , Virus Diseases/transmission , Blood Banks/standards , Blood Donors/statistics & numerical data , Cross-Sectional Studies , Deltaretrovirus Infections/epidemiology , Deltaretrovirus Infections/transmission , Demography , HIV Infections/epidemiology , HIV Infections/transmission , Hepatitis B/epidemiology , Hepatitis B/transmission , Hepatitis C/epidemiology , Hepatitis C/transmission , Humans , Incidence , Prevalence , Risk , United States/epidemiology
15.
Transfusion ; 45(4): 480-6, 2005 Apr.
Article En | MEDLINE | ID: mdl-15819666

BACKGROUND: The US West Nile virus (WNV) epidemic in the summer and fall of 2002 included the first documented cases of transfusion-transmitted WNV infection. In December 2002, the FDA supported a voluntary market withdrawal by the blood banking community of frozen blood components collected in WNV high-activity areas. At the time, the prevalence of viremia and serologic markers for WNV in the blood supply was undefined. STUDY DESIGN AND METHODS: In collaboration with America's Blood Centers, 1468 frozen plasma components (of approx. 60,000 frozen units voluntarily withdrawn from the market) were selectively retrieved from the peak epidemic regions and season (June 23, 2002-September 28, 2002). These units were unlinked, subaliquoted, and tested by WNV enzyme immunoassays (EIAs; Focus Technologies and Abbott Laboratories) and nucleic acid amplification tests (NATs; Gen-Probe Inc. and Roche Molecular Systems). RESULTS: Of the 1468 EIA results from Abbott and Focus, 7 were anti-immunoglobulin M (IgM)- and anti-immunoglobulin G (IgG)-reactive by both assays, 8 and 1 were IgM-only-reactive, and 8 and 23 were IgG-only-reactive, respectively. NAT by Gen-Probe and Roche Molecular Systems yielded one RNA-positive, antibody-negative unit containing approximately 440 RNA copies per mL. An additional 10-fold replicate NAT testing by Gen-Probe on 14 of 15 IgM-reactive specimens yielded 2 additional IgM- and IgG-reactive units with low-level viremia (i.e., 7/10 and 2/10 replicates tested reactive). CONCLUSION: The prevalence of acute (RNA-positive) and recent (IgM-seroreactive) WNV infections indicates that transfusion risk in high-risk areas could have been considerable and that voluntary market withdrawal of frozen components likely averted some WNV transfusion transmissions. The existence of very-low-level viremic units raises concerns, because WNV minipool NAT screening will miss such units and individual NAT may not completely correct this situation.


Blood Banks , Plasma/virology , West Nile Fever/blood , West Nile Fever/epidemiology , West Nile virus/isolation & purification , Antibodies, Viral/blood , Consumer Product Safety , Disease Outbreaks , Humans , Incidence , RNA, Viral/analysis , Risk Factors , Seroepidemiologic Studies , West Nile Fever/immunology , West Nile virus/genetics , West Nile virus/immunology
16.
Vox Sang ; 88(2): 114-21, 2005 Feb.
Article En | MEDLINE | ID: mdl-15720609

BACKGROUND AND OBJECTIVES: Converting first-time donors to become regular donors continues to be a challenge facing blood centres. We examined whether first-time donors with frequent return in the first 12 months were more likely to become regular donors. SUBJECTS AND METHODS: The donation histories of 179 409 community whole-blood donors, whose first-time donation in 1991 was negative on donor screening tests, were evaluated. Donors were categorized by the number of donations made in the 12 months after (and including) their first donation. The donor return pattern in the subsequent 6 years, and its association with first-year donation frequency and demographics, was evaluated by using logistic regression analysis. A 'regular donor' was defined as one who returned to donate in at least 4 of the 6 years of follow-up. RESULTS: First-year donation frequency was significantly correlated with long-term donor return (P < 0.0001). Among those giving 1, 2, 3, 4 and > or = 5 donations in the first year, 4%, 11%, 21%, 32% and 42%, respectively, became regular donors (P < 0.0001). Similar associations between donation pattern and donor return behaviour were observed after adjusting for demographic variables (P < 0.0001). CONCLUSIONS: Strategies aimed at encouraging current donors to donate more frequently during the first year may help to establish a regular donation behaviour.


Blood Donors/supply & distribution , Age Factors , Behavior , Blood Donors/psychology , Education , Humans , Regression Analysis , Sex Factors
17.
Br J Cancer ; 91(10): 1800-7, 2004 Nov 15.
Article En | MEDLINE | ID: mdl-15505620

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil.


Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Doxorubicin/pharmacology , Neoplasm Invasiveness/pathology , Paclitaxel/pharmacology , Adult , Breast Neoplasms/pathology , Cell Adhesion/drug effects , Cell Movement/drug effects , Doxorubicin/administration & dosage , Drug Resistance, Neoplasm , Female , Humans , Paclitaxel/administration & dosage , Phenotype , Selection, Genetic
18.
Transfusion ; 44(8): 1243-51, 2004 Aug.
Article En | MEDLINE | ID: mdl-15265131

BACKGROUND: Increasing concern about transfusion transmission of variant Creutzfeldt-Jakob disease has resulted in indefinite deferral of transfused donors in France and the UK. Little is known, however, about the impact of indefinite deferral of transfused donors on blood safety and availability in the US. STUDY DESIGN AND METHODS: Data were collected on allogeneic donations at five US blood centers during 1991 through 2000. Donation characteristics, prevalence, and incidence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were compared between transfused and nontransfused donors. Unreported deferrable risk (UDR) and reasons to donate were evaluated with data from a mail survey. RESULTS: Transfusion history was reported by 4.2 percent of donors. Prevalence and incidence of HIV and HBV were comparable between transfused and nontransfused donors. Although HCV incidence was similar in both groups, HCV prevalence was nearly three times higher in transfused than in nontransfused first-time donors. UDR and reasons to donate were similar in the two groups, except transfused donors were less likely to donate for screening test results (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). CONCLUSION: Transfused and nontransfused donors had similar viral incidence and comparable UDR, suggesting that indefinite deferral of transfused donors would unlikely improve blood safety. Until more is known about the prevalence and transfusion transmissibility of emerging agents, indefinite deferral of previously transfused donors in the US does not appear warranted.


Blood Donors , Transfusion Reaction , Adult , Aged , Biomarkers , Female , Humans , Male , Middle Aged , Risk
19.
Anticancer Res ; 24(2A): 473-82, 2004.
Article En | MEDLINE | ID: mdl-15152946

BACKGROUND: Bcl-2, an anti-apoptotic protein, is frequently associated with favourable prognosis in breast cancer. The potential role of mcl-1, another bcl-2 family member, in breast cancer has not yet been defined. PATIENTS AND METHODS: This study examined the expression of mcl-1 and bcl-2 in 170 cases of invasive primary breast carcinoma, using reverse-transcriptase polymerase chain reaction and immunohistochemical analyses. RESULTS: Expression of bcl-2 mRNA and protein were found to be favourably associated with outcome for patients, supporting a prognostic role for bcl-2 in breast cancer, whereas mcl-1 expression, at the mRNA or protein level, did not correlate with tumour size, grade, lymph node or ER status, age of patient at diagnosis, or disease outcome. CONCLUSION: As these analyses of mcl-1 expression may have co-detected mcl-1(S/deltaTM) (a more recently identified, shorter variant, that may be pro-apoptotic) with the anti-apoptotic wild-type of mcl-1, it is possible that future studies may indicate some significant clinical correlations if the isoforms can be independently investigated.


Breast Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Middle Aged , Myeloid Cell Leukemia Sequence 1 Protein , Neoplasm Proteins/genetics , Neoplasm Staging , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics
20.
Transfusion ; 43(9): 1260-8, 2003 Sep.
Article En | MEDLINE | ID: mdl-12919429

BACKGROUND: As part of assessing the possibility of transfusion transmission of human herpesvirus 8 (HHV-8 or Kaposi's sarcoma-associated herpesvirus), HHV-8 seroprevalence was estimated among US blood donors, the performance of HHV-8 serologic tests was compared, and the presence of HHV-8 DNA was tested for in donated blood. STUDY DESIGN AND METHODS: Replicate panels of 1040 plasma specimens prepared from 1000 US blood donors (collected in 1994 and 1995) and 21 Kaposi's sarcoma patients were tested for antibodies to HHV-8 in six laboratories. HHV-8 PCR was performed on blood samples from 138 donors, including all 33 who tested seropositive in at least two laboratories and 22 who tested positive in at least one. RESULTS: The estimated HHV-8 seroprevalence among US blood donors was 3.5 percent (95% CI, 1.2%-9.8%) by a conditional dependence latent-class model, 3.0 percent (95% CI, 2.0%-4.6%) by a conditional independence latent-class model, and 3.3 percent (95% CI, 2.3%-4.6%) by use of a consensus-derived gold standard (specimens positive in two or more laboratories); the conditional dependence model best fit the data. In this model, laboratory specificities ranged from 96.6 to 100 percent. Sensitivities ranged widely, but with overlapping 95 percent CIs. HHV-8 DNA was detected in blood from none of 138 donors evaluated. CONCLUSIONS: Medical and behavioral screening does not eliminate HHV-8-seropositive persons from the US blood donor pool, but no viral DNA was found in donor blood. Further studies of much larger numbers of seropositive individuals will be required to more completely assess the rate of viremia and possibility of HHV-8 transfusion transmission. Current data do not indicate a need to screen US blood donors for HHV-8.


Blood Donors/statistics & numerical data , Herpesviridae Infections/blood , Herpesviridae Infections/epidemiology , Herpesvirus 8, Human/isolation & purification , Antibodies, Viral/blood , Blood Banks/standards , Herpesviridae Infections/transmission , Herpesvirus 8, Human/immunology , Humans , Reference Standards , Sensitivity and Specificity , Seroepidemiologic Studies , United States/epidemiology
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