Combo with "Epstein Barr Virus" and 1 other – Flashcards

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how do viruses that infect the circulatory, reticuloendothelial, and lymphatic systems cause disease? 3
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-remain silent -cause hyper proliferation -cellular dysfunction in these organ systems.
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Diseases caused by these viruses 4
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Cancer Birth Defects Immunosuppression Cardiac dysfunction
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Epstein Barr Virus viral family genome
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Herpesviridae family member Enveloped dsDNA virus
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Epstein Barr Virus mechanism of infection
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Uses C3d component of complement system for attachment and entry. Replication in epithelial and B CELLS
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Epstein Barr Virus - MOA 5 steps
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1. infect B cell 2. cause B cell to proliferate and told to produce antibodies to EBV virus and other random antigens= heterophiles antibodies 3. T cells rec. infection and being fighting off infection 4. few b cells escape forming memory b cells -have EBV virus in genome in latent phase 5. stim--> moment from latency to productive phase--> asymptomatic shedding in saliva
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Epstein Barr Virus - Virology Heterophile Antibodies
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random antibodies to seemingly random antigens
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Epstein Barr Virus - Virology Latency -allows for what? 2
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ALL herpes viruses allow for cancer and delayed symptoms
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Genes Involved in EBV Carcinogenesis
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genes produced during latency that allow for EBV to cause cancer
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Genes Involved in EBV Carcinogenesis Latent Membrane Protein 1 (LMP1) -MOA= cancer -structure
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6 transmembrane-spanning domains CD40 Homologue Constitutively Active Receptor -Increased Growth - Suppressed Apoptosis
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Genes Involved in EBV Carcinogenesis Latent Membrane Protein 2 (LMP2) -MOA= cancer
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Increased Growth of B cells
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Genes Involved in EBV Carcinogenesis Epstein Barr Virus Nuclear Antigen 1 (EBNA1) -MOA= cancer
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-Transactivation of EBV transforming genes (LMP1 and LMP2) - Inhibition of Apoptosis
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Epstein-Barr Virus transmission
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saliva high prevalent 90%
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Epstein-Barr Virus primary infection population WW US
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Worldwide - before 5 years of age United States -adolescence and early adulthood
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Epstein-Barr Virus factors contributing to cancer? 3
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-Immunosuppression ex. malaria -Genetic predisposition -Environmental factors
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Epstein-Barr Virus Infectious Mononucleosis symptoms 5
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fever malaise exudative pharyngitis splenomegaly tender lymphadenitis
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Epstein-Barr Virus Infectious Mononucleosis - biomarker
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Heterophile antibodies
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Epstein-Barr Virus Infectious Mononucleosis main pop infected?
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Most common in young adulthood and in industrialized countries.
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Epstein-Barr Virus Infectious Mononucleosis complications
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splenic rupture
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Epstein-Barr Virus Infectious Mononucleosis main cause of symptoms?
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immune targeting of infected B cells
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Epstein-Barr Virus Infectious Mononucleosis when do you see a rash?
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Rash - often accompanied by ampicillin treatment -may form complexes= rash
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Epstein-Barr Virus progression symptoms
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1. fever + malasia + fatigue +virus shedding 2. lymphadenopathy + hepatospenomegaly +pharangitis
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Epstein-Barr Virus Infectious Mononucleosis progression of antigen seen? progression antibodies
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EA = EBV Early Antigen (lytic) VCA = EBV Viral Capsid Antigen (lytic) EBNA = Epstein Barr Nuclear Antigen (latent) 1. anti EA antibody 2. anti VCA 3. IgM 4. IgG + anti ebna
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Epstein-Barr Virus Infectious Mononucleosis diagnosis
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-mono spot -antibodies to EBV -downey cells
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Epstein-Barr Virus Infectious Mononucleosis diagnosis -mono spot
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Heterophiles Antibodies -agglutinate sheep or horse RBC.
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Epstein-Barr Virus Infectious Mononucleosis diagnosis -antibodies of EBV
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IgM to Viral Capsid Antigen (VCA) demonstrates primary EBV infection.
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Epstein-Barr Virus Infectious Mononucleosis diagnosis -downey cells appearance 3 what are they
Epstein-Barr Virus  Infectious Mononucleosis diagnosis  -downey cells  appearance 3 what are they
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Atypical T cell Vacuoles Altered Nucleus Indented Cell Margin
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Epstein-Barr Virus Infectious Mononucleosis -treatment 2
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1. Rest and Hydration 2. Avoid strenuous activity to avoid splenic rupture. Anti-virals (acyclovir) - inhibit the viral polymerase - not used because cause is not virus but immune response to infected B cells 3. Avoid strenuous activity to avoid splenic rupture.
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Epstein-Barr Virus Infectious Mononucleosis vaccine
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none
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Epstein-Barr Virus oral hairy leukoplakia -common in what patients
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-common in immunosuppressed (HIV) ~300 CD4 T-cell/mm3= seen early
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Epstein-Barr Virus oral hairy leukoplakia -stage virus in in cycle
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Active EBV replication
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Epstein-Barr Virus oral hairy leukoplakia treatment 2
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Antiherpetic drugs= acyclovir -b/c main cause= replicating virus Podophyllin resin
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Epstein-Barr Virus Cancer Burkitt's Lymphoma -cause -main symptoms
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B-cell origin Often presenting in the jaw of children (endemic form)
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Epstein-Barr Virus Cancer Burkitt's Lymphoma -location seen in world
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W africa
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Epstein-Barr Virus Cancer Burkitt's Lymphoma -genetic cause -result?
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tranlocation event moving MYC gene from chromosome 8--> 14 up reg. E2F increase rate of cell cycle movement from G1--> S phase makes it the most rapidly progression tumor
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Epstein-Barr Virus Cancer Burkitt's Lymphoma -treatment
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Treated with chemotherapy (70-80% cure rates).
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Epstein-Barr Virus Cancer Burkitt's Lymphoma -endemic ass. -US ass
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100% with EBV= endemic 20%= US
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Epstein-Barr Virus Cancer Burkitt's Lymphoma cofactors 2
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Chronic Malaria - endemic Immune Suppression
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Epstein-Barr Virus Cancer Hodgkin's Disease -cause -genetics?
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B-cell origin Not linked to specific chromosomal translocation events.
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Epstein-Barr Virus Cancer Hodgkin's Disease symptoms
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-Nontender, palpable, lymphandenopathy in neck supraclavicular, and/or axilla. -Commonly enlargement of lymph nodes deep within chest (medistinal adenopathy). Approximately 1/3 of patients -display fever -night sweats - weight loss
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Epstein-Barr Virus Cancer Hodgkin's Disease Reed-Sternberg cell -appearance
Epstein-Barr Virus Cancer   Hodgkin's Disease  Reed-Sternberg cell -appearance
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a large cell with two or more nuclei or nuclear lobes, each of which contains a large eosinophilic nucleolus classic presentation hodgkins disease
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Epstein-Barr Virus Cancer Hodgkin's Disease treatment patients with EBV having this cancer?
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-radiotherapy and/or chemotherapy. -Localized Hodgkin's disease is cured in greater than 90% of patients. 20-40% contain proliferation of EBV-infected cells.
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Epstein-Barr Virus Cancer Nasopharyngeal Carcinoma -location -cell involved?
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Originates in the nasopharynx. Epithelial cell cancer.
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Epstein-Barr Virus Cancer Nasopharyngeal Carcinoma symptoms 3
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Facial pain Fullness in sinuses and throat Hearing loss
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Epstein-Barr Virus Cancer Nasopharyngeal Carcinoma location globally
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SE asia
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Epstein-Barr Virus Cancer Nasopharyngeal Carcinoma treatment
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Nasopharyngeal carcinomas are treated through chemotherapy and radiation treatment regimens.
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Epstein-Barr Virus Cancer Nasopharyngeal Carcinoma cofactors 2
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-genetics -diet
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Epstein-Barr Virus Cancer Post-transplantation Lymphoproliferative Disorder (PTLD) -association -spread -type of cell
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Abnormal proliferation of lymphoid cells in a transplant patient. malignant or benign
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Epstein-Barr Virus Cancer Post-transplantation Lymphoproliferative Disorder (PTLD) symptoms 4
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-fever - fatigue - weight loss - progressive encephalopathy
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Epstein-Barr Virus Cancer Post-transplantation Lymphoproliferative Disorder (PTLD) main risk factors
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transplant
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Epstein-Barr Virus Cancer Post-transplantation Lymphoproliferative Disorder (PTLD) diangosis
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Histological analysis of tissue. Detection of EBV genomes (in situ hybridization)
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Epstein-Barr Virus Cancer Post-transplantation Lymphoproliferative Disorder (PTLD) treatment progression 3 steps
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1. 1st Reduce Immunosuppression 2. 2nd Treatment with Rituximab (mouse human chimeric anti-CD20 antibody.) 3. 3rd conventional chemotherapy
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Cytomegalovirus Diseases -based on what
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demographics patients -Normal= asym or mono -baby of sero negative mom= cytomegalic inclusion disease -AIDS or immunsuppres= multisigte symptomatic disease
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Cytomegalovirus (CMV) family genome sym in healthy people?
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Herpesviridae family Enveloped dsDNA Reactivation is rarely symptomatic in immunocompetent individuals.
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Cytomegalovirus (CMV) location of viral replication
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1. Mucosal epithelium 2. Viremia
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Cytomegalovirus (CMV) latency in what cells
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monocytes
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Cytomegalovirus (CMV) transmission 4
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-Saliva -Breast milk -Urine -Fomites -Sexual contact
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Cytomegalovirus (CMV) diagnosis 2
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-Detection of viral DNA or virus culture from diseased tissue= not necessarily acute b/c patient can shed for years w/out sym -Seroconversion= timing matters and multiple samples
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CMV Antivirals 1st line 2 antivirals - negatives of these drugs?
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Gancyclovir Valganciclovir toxicity to bone marrow + drug related neutropenia
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CMV Antivirals 1st line -Gancyclovir
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converted to viral polymerase inhibitor by CMV enzymes (i.v. or oral).
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CMV Antivirals 1st line -Valganciclovir
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converted to gancyclovir within the body. Increased bioavailability. (oral)
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CMV Antivirals 2nd line -name 2
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Cidofovir Foscarnet given if gancyclovier or valganciclovir don't work MORE toxic
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CMV Antivirals 2nd Cidofovir
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converted to viral polymerase inhibitor by cellular enzymes. More toxic than gancyclovir .(i.v.)
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CMV Antivirals 2nd Foscarnet
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direct inhibitor of the CMV polymerase. renal toxicity. (i.v.)
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CMV Infectious Mononucleosis-Like Illness -incubation -symptoms 5 and duration
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Incubation period 20-60 days Symptoms duration 2-6 weeks -Fever -Fatigue -Pharyngitis (usually non exudative) -Abnormal T cells -No heterophile antibody production
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CMV Infectious Mononucleosis-Like Illness infection seen in what pop?
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primary infection healthy individuals
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CMV Cytomegalic Inclusion Body Disease -how common -in what pop. ass. with -mortality rate
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Occurs in ~5% of congenital CMV infections. Most common with primary infections in mom during pregnancy Mortality rate in severe cases is 20-30% CONGENITAL INFECTION
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CMV Cytomegalic Inclusion Body Disease -symptoms -when are they seen? 7
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Infants that are asymptomatic at birth can develop abnormalities later in life. -Hepatosplenomegaly -Jaundice -Petechiae/Rash -Microcephaly -Growth retardation -Inguinal hernias -Chorioretinitis
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CMV- Cytomegalic Inclusion Body Disease how common in US
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Most common congenital viral infection 30,000 children per year in US
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CMV- Cytomegalic Inclusion Body Disease how does it occur?
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30 - 50% women childbearing age seronegative for CMV. - 1-4% of these women will be exposed during pregnancy. Risk of transmission from primary CMV infection during pregnancy = 1/3
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Cytomegalic Inclusion Disease prevention 3 and what pop
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for women seronegative at time of pregnancy prevent woman from getting -handwahsing -avoid sharing drinks + toothbrushes with children -avoid kissing children
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Cytomegalic Inclusion Disease treatment
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Maternal treatment with CMV immunoglobulin during pregnancy currently under investigation
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CMV in Immunosuppressed Populations what 2 groups effected?
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-highest risk in 1-4 months following transplant - predominant disease in AIDS patients 50-100 T cells/ ul
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CMV in Immunosuppressed Populations main symptoms
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Spiking Fever (100- 104 ºF)
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CMV in Immunosuppressed Populations 2 sources
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-reactivation of latent CMV -transplanted organ
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CMV disease transplant patients 3 disease
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-CMV pneumonitis -GI disease -graph vs host
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CMV disease transplant patients CMV pneumonitis -symptoms
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Fever Hypoxia Interstitial Lung Infiltrates
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CMV disease transplant patients -GI disease symptoms 4 complication
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Diarrhea Abdominal Pain Nausea Vomiting Complication: perforation and hemorrhage of GI epithelium
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CMV disease AIDS patients 3 diseases
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CMV retinitis GI CMV pneumonitis
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CMV disease AIDS patients CMV retinitis -symptoms 3 -diagnosis
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Blurred Vision "Floaters" White lesions Lesions with irregular, white necrotic border Diagnosis Pupil dilation and ophthalmoscope examination
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CMV in Immunosuppressed Populations prevention organ transplant prevention 3
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-Donor matching -Prophylaxis or preemptive therapy with antivirals -CMV immunoglobin
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CMV in Immunosuppressed Populations prevention AIDS
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Maintenance therapy with antivirals when reaching a threshhold level of CD4+ T-cells.
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CMV in Immunosuppressed Populations treatment indications
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immunocompromised patients with severe disease are treated with I.V. antivirals. basically watch patient for symptoms
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