PBL #5

Question 1

What are the causes of pulmonary nodules?

Answer 1

• Malignant neoplasms:
  
  • non-small cell lung cancer, Small cell carcinoma, Solitary metastasis, Primary pulmonary lymphoma, Primary pulmonary carcinoid, Malignant teratoma, Pulmonary blastoma
• Benign neoplasms:
  
  • Hamartoma, Chondroma, Hemangioma, Arteriovenous malformation, Fibroma, Neural tumor, Sclerosing hemangioma
• Infections:
  
  • Granulomatous infections: T, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, pulmonary aspergilloma
  • Bacterial infection: nocardiosis, antinomycosis, round pneumonia
• Measles
• Septic emboli
• Abscess
• Congenital causes: bronchogenic cyst, bronchial atresia w/ mucoid impaction, sequestration
• Other stuff: amyloid, sarcoidosis, RA, granulomatosis with polyangiitis

Question 2

What is the prevalence of pulmonary nodules?

Answer 2

• Solitary pulmonary nodule found on up to 0.2% of all chest films
• Lung nodules found on up to 50% of all lung CT scans

Question 3

What is the significance of calcification and cavitation of a pulmonary nodule?

Answer 3

• Calcification:
  
  • Usually indicates a benign disease.
  • Benign patterns of calcification: central nidus, laminated, diffuse, popcorn.
    
    • If it has 1 of these 4 patterns and is < 3 cm, it is most likely benign.
• Cavitation:
  
  • gas-filled area on the lung in the center of a nodule or area of consolidation (lung tissue filled with water)produced by the expulsion of a necrotic part of a lesion
  • Noninfectious disease associations: Malignancy, granulomatosis with polyangiitis (Wegener’s), pulmonary infarct due to embolism.
  • Infectious associations: Necrotizing pneumonias and lung abscesses, Mycobacterium tuberculosis, Fungal infections, septic emboli.

Question 4

What are the organisms responsible for pulmonary infections in HIV+ patients with normal CD4+ counts?

Answer 4

• Strep. Pneumoniae
  
  • Gm positive, Catalase neg, Alpha Hemolytic, Bile-Esmulin negative, Optochin Susceptible, Quellung positive, IgA Protease

Question 5

What are the organisms responsible for pulmonary infections in HIV+ patients with CD4+ counts less than 200?

Answer 5

• Pneumocystis jirovecii pneumonia (PCP)
• Histoplasmosis (Histoplasma capsulatum)
  
  • Fungus found in bird/bat fecal material, and soil.
• Toxoplasmosis (Toxoplasma gondii Encephalitis)
  
  • Parasite that usually comes from cats (they can only reproduce in cats → shed in cat’s feces )
• Invasive Aspergillosis (Aspergillus)
  
  • common mold (a type of fungus) that lives indoors and outdoors

Question 6

What are the organisms responsible for pulmonary infections in HIV+ patients with CD4+ counts less than 50?

Answer 6

• Mycobacterium avium infection
• Interstitial Pneumonia- CMV
  
  • Cytomegalovirus, HHV-5, dsDNA

Question 7

What are the agents that can cause TB?

Answer 7

• M. tuberculosis - cause great majority of human disease
• M. africanum - causes human tuberculosis (TB) in tropical Africa
• M. bovis - primarily isolated from cattle but causes 1%-2% of TB disease

Question 8

What are the parameters of a tuberculin test (define PPD)? How are they interpreted?

Answer 8

• PPD test for purified protein derivative
• 5+ mm is positive in:
  
  • HIV-positive person
  • Persons with recent contacts with a TB patient
  • Persons with nodular or fibrotic changes on chest X-ray consistent with old healed TB
  • Patients with organ transplants, and other immunosuppressed patients
• 10+ mm is positive in:
  
  • Recent arrivals (less than five years) from high-prevalence countries
  • IV drug users
  • Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters, etc.)
  • Mycobacteriology lab personnel
  • Persons with clinical conditions that place them at high risk (e.g., DM, prolonged corticosteroid therapy, leukemia, ESRD, chronic malabsorption syndromes, etc.)
  • Children <4 yoa, or children & adolescents exposed to adults in high-risk categories
• 15 mm or more is positive in:
  
  • Persons with no known risk factors for TB

Question 9

How do you calculate and interpret a positive predictive value?

Answer 9

• Calculate PPV:
  
  • TP/(TP + FP)
• IF PPV is high → more likely that the patient actually has the condition he/she has tested positive for
  
  • ​PPV increases in high prevalence settings
• IF PPV is low → more likely that your patient has tested FALSELY positive, and does not actually have the condition

Question 10

What is the MOA of Isoniazid?

Answer 10

• inhibits the synthesis of mycolic acids (essential component of bacterial cell wall)

Question 11

What is the MOA of Rifamycins?

Answer 11

• Inhibits DNA-dependent RNA polymerase.
• Four R’s:
  
  • Ramps up P-450
  • Red body fluids
  • Rapid resistance
  • RNA polymerase inhibitor

Question 12

What is the MOA of Pyrazinamide?

Answer 12

• Unknown.
• Thought to acidify intracellular environment via conversion to pyrazinoic acid.

Question 13

What is the MOA of Ethambutol?

Answer 13

• Decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase

Question 14

What is the MOA of Pyridoxine?

Answer 14

• Vitamin B₆ supplement
• Given with Isoniazid to prevent neurotoxicity.

Question 15

What is the MOA of Streptomycin?

Answer 15

• Protein synthesis inhibitor:
  
  • binds to the small 16S rRNA of the 30S subunit of the bacterial ribosome
  • causes codon misreading
• Inhibits both Gram-positive and Gram-negative bacteria (bactericidal)
• First aminoglycosides discovered.

Question 16

What is the MOA of HIV Protease Inhibitors? Examples?

Answer 16

• Example Drugs: Ritonavir, Indinavir, Amprenavir, Saquinavir, Lopinavir, Tipranavir, Atazanavir
  
  • ​End in –navir
• MOA: Blocks HIV Protease → unable to cleave HIV polypeptide into functional groups.

Question 17

What is the MOA of HIV Nucleoside Reverse Transcriptase Inhibitors (NRTIs)? Examples?

Answer 17

• Example Drugs: Zidovudine (AZT), Abacavir, Emtricitabine, Lamivudine
• MOA: Inhibits Reverse Transcriptase which prevent conversion of HIV RNA → cDNA.
  
  • require phosphorylation to be active

Question 18

What is the MOA of HIV Nucleotide Reverse Transcriptase Inhibitors (NRTIs)? Examples?

Answer 18

• MOA: competitively inhibit nucleotide binding to reverse transcriptase
  
  • incorporated into viral DNA chain → causing termination
  • requires phosphorylation to become active
• Example: Tenofovir

Question 19

What is the MOA of HIV Non-Nucleotide Reverse Transcriptase Inhibitors (NNRTIs)? Examples?

Answer 19

• MOA: bind directly to reverse transcriptase and inhibit enzyme production of viral DNA
• Examples: Efavirenz, Etravirine

Question 20

What is the MOA of HIV Integrase Inhibitors? Examples?

Answer 20

• MOA: binds to integrase → inhibiting strand transfer and the final step of provirus integration
• Examples: Raltegravir

Question 21

What is the MOA of HIV CCR5 Antagonists? Examples?

Answer 21

• MOA: Binds CCR5 receptor on surface of T-cells → inhibiting interaction with gp120 on HIV
• Examples: Maraviroc

Question 22

What is the MOA of HIV Fusion Inhibitors? Examples?

Answer 22

• MOA: Binds gp41 on viral envelope → inhibiting conformational change/viral fusion
• Examples: Enfuvirtide

Question 23

What does public health surveillance for TB consist of?

Answer 23

• Immigrants moving to the US undergo a health screening, specifically children must meet the following requirements for TB.
• <2 years old: No tests unless child has signs or symptoms of TB or has been in contact with a person with TB.
• 2-14 years old: (tuberculin skin test) TST or (interferon-gamma release assay) IGRA* (if positive) → Chest X-ray* (if positive) → sputum smear and cultures (if positive) → DST (drug sensitivity testing) → DOT (daily observed therapy)
• 15 years old & up: Chest X-ray* (if positive) → sputum smear and cultures (if positive) → DST → DOT

Question 24

What are the Minnesota reporting requirements for latent TB and active TB?

Answer 24

• Latent TB not a reportable condition in MN
• Active TB (confirmed and suspected cases) reportable condition in MN
  
  • Confirmed or suspected cases must be reported in <24 hrs
    
    • Isolation of M. tuberculosis
  • Both pulmonary and extrapulmonary cases reportable

Question 25

What is some of the evolving genetic testing being used as new drugs are developed to target HIV?

Answer 25

• HIV Drug Resistance Testing
  
  • standard genotypic testing: looking for mutations in reverse transcriptase (RT) and protease (PR) genes
  • genotypic testing of integrase and envelope proteins if this is a concern
• HIV resistance testing
  
  • CCR5 Mutation Homozygotes are resistant to ONLY R5 Tropism of HIV
  • CCR5 Mutation Heterozygotes have slower progression of ONLY R5 Tropism
• HLA-B*5701 testing is recommended for any patients who are going to be put on Abacavir (NRTI used to treat HIV) to avoid Hypersensitivity Reactions.