AVS 471 Therapeutics in Livestock

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AVS 471Therapeutics in Livestock

• Lecture 12

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Introduction

• Topics/Learning Objectives
• Responsible use of therapeutics in livestock
• Off-label use of drug products
• AMDUCA
• Beef Quality Assurance Program (BQA)
• Mechanisms of action for commonly used
  antibiotics in livestock practice
• Mechanism of action of other commonly used
  therapeutic agents

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Questions to ask before using a drug?

• What type of infection am I treating?
• Viral
• Bacterial
• Parasitic
• Where am I trying to treat the infection?
• Abscess
• Bloodstream
• Central Nervous System
• Mammary Gland

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Questions to ask before using a drug?

• Is the drug approved for use in food producing
  animals?
• What is the meat and/or milk withholding of the
  drug to be used?
• If the drug is to be used in an extralabel
  fashion, do you have a good reason for doing so?
• AMDUCA

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OTC versus Prescription

• Prescription Drugs
• Anything with a label that states
• Any drug that is used in an Extra-label fashion
• Over The Counter Drugs
• Can be purchased and administered (according to
  label directions) without a prescription.

Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
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AMDUCA

• Animal Medicinal Drug Use Clarification Act
• Guidelines for the Extralabel Drug Use (ELDU)
• http//www.avma.org/scienact/amduca/amduca1.asp

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Important Points from AMDUCA

• ELDU permitted only under veterinary supervision
• ELDU for therapeutic purposes only
• ELDU is prohibited for drugs used in feed.
• ELDU cannot be applied to drugs used to enhance
  production.

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Important Points from AMDUCA

• Certain drugs are prohibited for use in food
  producing animals.
• Chloramphenicol, Clenbuterol, Diethylstilbestrol,
  Dimetridazole, Pronidazole, Other
  Nitroimidazoles, Furazolidones (except approved
  topicals), Nitrofurazone (except approved
  topicals), Sulfonamide drugs in lactating dairy
  cows (except approved use of sulfadimethoxine,
  sulfabromomethazine, and sulfaethoxypyridazine),
  Fluoroquinolones, Glycopepetides
• ELDU is not permitted if it results in a
  violative food residue, or any residue which may
  present a risk to public health.

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Beef/Dairy Quality Assurance

• Objectives
• Prevent inappropriate
• Biologics
• Therapeutics
• Handling
• Quality Assurance (Goals)
• Residue Avoidance
• Improve milk/meat quality
• Minimize injection site lesions

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National Cattlemans Beef Associations BQA -
National Guidelines

• Processing/Treatment and Records
• Maintenance of treatment records
• Individual Animal or group identification
• Date Treated
• Product administered and manufacturers lot and
  serial
• Dosage used
• Route and location of administration
• Earliest date animal will have cleared withdrawal
  time

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National Cattlemans Beef Associations BQA -
National Guidelines

• Processing/Treatment and Records
• Cattle processed as a group
• All cattle within group identified as a group
• Date treated
• Product administered and manufacturers lot and
  serial
• Dosage used
• Route and location of administration
• Earliest date animal will have cleared withdrawal
  time

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National Cattlemans Beef Associations BQA -
National Guidelines

• Injectable Animal Health Products
• Products labeled for subcutaneous (SQ) use should
  be administered ahead of the shoulder
• All products labeled for intramuscular (IM) use
  shall be given in the neck region only.
• All products cause tissue damage when injected
  IM, therefore IM usage should be avoided.
• Products cleared for SQ, IV or oral
  administration are recommended
• Products with low dosage formulations are
  recommended.
• No greater than 10 ml of product should be
  administered per IM injection site.

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Other Considerations

• Choose the correct needle
• SQ 16 or 18 gauge, 1/2-3/4
• IM 16 or 18 gauge, 1-1.5
• 14 gauge not recommended
• Increased tissue trauma
• More likely to get drainage from site
• Sharp needles (replace needles regularly)
• Correct Injection Site
• Triangular mass of the neck muscle
• NEVER INJECT IN THE HINDQUARTERS

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Appropriate Injection Sites
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Other Considerations

• Handle vaccines and Medications with care
• Store in refrigerator
• Dont mix two different products in same syringe
• Use separate needles for filling syringes and
  injecting (minimizes product contamination and
  maintains use of sharp needles)
• Sanitation is essential
• Disinfectant residues in syringes can activate
  MLV vaccines

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Antimicrobial Therapy
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Antimicrobial Therapy

• Definitions
• Antimicrobial - kills microorganisms or inhibits
  their multiplication/growth
• Antibiotic - a chemical produced by a
  microorganism that has the ability in dilute
  solutions to inhibit microbial growth or kill
  microorganisms
• Minimum Inhibitory Concentration (MIC) - the
  lowest concentration of drug that inhibits
  bacterial growth
• Minimum Bacteriocidal Concentration - the lowest
  concentration of a drug that kills 99.9 of the
  bacteria

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Antimicrobial Therapy

• Definitions
• Bacteriocidal - an antibiotic having a MBCMIC
  ratio lt 46
• Bacteriostatic - inhibit bacterial growth
• Post-antibiotic Effect - persistence of
  antimicrobial activity after drug concentrations
  have fallen below MIC
• Pharmacokinetics - the study of absorption,
  distribution, biotransformation, and excretion of
  drugs
• Pharmacodynamics - the study of the effects of
  drugs, mechanism of action (MOA), and
  concentration-effect relationships

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Antimicrobial Sensitivity Testing

• Agar Disk Diffusion
• Kirby-Bauer Disk Diffusion Test
• Mueller-Hinton Agar
• Paper disk impregnated with antibiotic
• Diameter of zone of inhibition is measured and
  correlates to the MIC
• Interpretation?
• Not standardized for veterinary pathogens
• Must use published standards to interpret
  sensitivity (differential diffusion rates of
  antibiotics)

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Mechanisms of Action of Commonly Used
Antimicrobial Agents Used in Livestock
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Inhibitors of Cell Wall Synthesis

• ?-lactam Antibiotics
• Penicillins
• Benzylpenicillins - Procaine penicillin G (PPG),
  benzathine penicillin, potassium penicillin
• Aminopenicillins - Ampicillin, Amoxicillin
  (Polyflex, Amoxi-Inject)
• Anti-staphylococcal penicillins - cloxacillin
  (Dariclox)
• Cephalosporins
• 1at generation - cephapirin sodium (Cefa-Lak,
  Cefa-Dry)
• 3rd generation - ceftiofur (Naxcel, Excenel)

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Inhibitors of Protein Synthesis

• Aminoglycosides
• Dihydrostreptomycin (Quartermaster)
• Tetracyclines
• Oxytetracylcine (LA-200)
• Chloramphenicols
• Florfenicol (Nu-Flor)

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Inhibitors of Protein Synthesis

• Macrolides
• Erythromycin (Erythro-100, Erythro-200,
  Erythro-36, Erythro-Dry)
• Tylosin (Tylan)
• Tilmicosin (Micotil)
• Lincosamides
• Lincomycin (Lincocin)
• Pirlimycin (Pirsue)

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Inhibitors of Intermediary Metabolism

• Sulfonamides
• Sulfadimethoxine (Albon, Albon-SR)

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Inhibitors of Nucleic Acid Synthesis

• Fluroquinolones
• Enrofloxacin (Baytril)

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Spectrum of Activity and Common Uses of
Antimicrobial Agents in Livestock
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Inhibitors of Cell Wall Synthesis

• ?-lactam Antibiotics
• Penicillins
• Spectrum Gram positive aerobes, obligate
  anaerobes, Staphylococcus aureus is usually
  resistant.
• Formulation Procaine Penicillin G - most
  commonly used
• Route of Administration IM, SQ
• Distribution Most tissues except CSF
• Dose Clinically useful dose is 3-5 times the
  label dose ? constitutes ELDU.
• Withdrawal Times Milk - 120 hours , Meat - 30
  days _at_ commonly used dosage.
• Adverse reactions Procaine reaction
• Uses Many pyogenic infections in ruminants,
  camelids and swine

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Inhibitors of Cell Wall Synthesis

• ?-lactam Antibiotics
• Aminopenicillins
• Spectrum Gram positive aerobes, some gram
  negative organisms
• Formulations Ampicillin, Amoxicillin
• Route of Administration IM, SQ, Intramammary
• Distribution Most tissues except CSF
• Withdrawal Times Amoxi-Inject (Milk - 96 hours,
  Meat - 25 days) Polyflex (Milk - 48 hours, Meat
  - 6 days) Amoxi-Mast (Milk - 60 hours, Meat -
  12 days) .
• Uses Foot Rot, Shipping Fever, Mastitis

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Inhibitors of Cell Wall Synthesis

• ?-lactam Antibiotics
• Antistaphylococcal Penicillins
• Spectrum Gram positive aerobes, obligate
  anaerobes, resistant to ?-lactamases produced by
  Staph. spp.
• Formulations Cloxacillin
• Route of Administration Intramammary
• Withdrawal Times Dari-Clox (Milk - 48 hours,
  Meat - 10 days) Dry-Clox (Meat 30 days)
• Uses Lactating and Dry cow mastitis pathogens

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Inhibitors of Cell Wall Synthesis

• ?-lactam Antibiotics
• Cephalosporins (1st Generation)
• Spectrum Gram positive bacteria, moderate gram
  negative spectra, ?-lactamase Staph. spp.
• Formulations Cephapirin
• Route of Administration Intramammary
• Withdrawal Times Cefa-Lak, Today (Milk - 96
  hours, Meat - 4 days) Cefa-Dri, Tomorrow (Milk
  - 72 hours, Meat - 42 days)
• Uses Lactating and Dry cow mastitis pathogens

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Inhibitors of Cell Wall Synthesis

• ?-lactam Antibiotics
• Cephalosporins (3rd Generation)
• Spectrum less gram positive spectra, excellent
  gram negative spectra
• Formulations Ceftiofur
• Route of Administration IM, SQ, IV
• Withdrawal Times Naxcel (Milk - 0 days, Meat -
  0 days) Excenel (Milk - 0 days Meat - 48
  hours)
• Uses Shipping Fever

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Inhibitors of Protein Synthesis

• Aminoglycosides
• Dihydrostreptomycin
• Mechanism Oxygen-dependent Bind 30-S ribosomal
  subunit ? misreading of genetic code
  Bacteriocidal Post-antibiotic effect Synergism
  with ?-lactams.
• Spectrum Gram negative bacteria (primarily) Not
  anaerobes
• Formulations Combined with procaine penicillin G
  in mastitis treatment tube. Dry cows only.
• Route of Administration Intramammary
• Withdrawal Times Quartermaster (Dry Cows, Meat
  60 days)
• Uses Dry cow therapy

Use of Gentamicin Strongly Discouraged in Food
Animals
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Inhibitors of Protein Synthesis

• Tetracyclines
• Oxytetracylcine
• Mechanism Bind 30-S ribosomal subunit prevent
  peptide chain formation Bacteriostatic
• Spectrum Gram negative and positive bacteria
  Chlamydia rickettsia spirochetes Mycoplasma
  protozoa
• Formulations Oxytetracycline 50, 100, and 200
• Route of Administration IV, IM, SQ
• Distribution Most tissues except CNS
• Withdrawal Times LA-200 (Milk - 96 hours, Meat
  - 28 days) Vary according to formulation, dose
  and route of administration.
• Uses Shipping Fever, Wooden Tongue,
  Pinkeye, Foot Rot, Diphtheria, Bacterial
  enteritis, Leptospirosis, Wound infections, Acute
  metritis.

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Inhibitors of Protein Synthesis

• Chloramphenicols
• Florfenicol
• Mechanism Bind 50-S ribosomal subunit
  Bacteriostatic
• Spectrum Gram positive and negative bacteria
  anaerobes rickettsia Chlamydia
• Formulations Florfenicol
• Route of Administration IM, SQ
• Distribution Lipophilic gt Most tissues and CNS
• Withdrawal Times Nu-Flor (Meat 28-38 days).
  Not approved for use in lactating dairy cattle
• Uses Shipping Fever

Only Legal Chloramphenicol Derivative for Use in
Livestock
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Inhibitors of Protein Synthesis

• Macrolides
• Erythromycin
• Mechanism Bind 50-S ribosomal subunit
  Bacteriostatic
• Spectrum Gram positive bacteria
• Formulations Erythro-100, Erythro-200,
  Erythro-36, Erythro-Dry
• Route of Administration IM, Intramammary
• Distribution Most tissues, Leukocytes, Not CNS
• Withdrawal Times Erythro-100,200 (Milk - 72
  hours Meat - Cattle 14 days, Sheep 3 days, Swine
  7 days) Erythro-36, Dry (Milk - 36 hours Meat -
  14 days)
• Uses Lactating and dry cow mastitis pathogens
  metritis Foot Rot Pneumonia (Shipping Fever)

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Inhibitors of Protein Synthesis

• Macrolides
• Tylosin
• Mechanism, Spectrum Distribution Similar to
  Erythromycin
• Formulations Tylan (Various concentrations),
  Water treatments for pigs
• Route of Administration IM, PO
• Withdrawal Times Not approved for use in
  lactating dairy cattle Meat - Cattle 21 days
  Swine 14 days
• Uses Shipping Fever Mycoplasma pneumonia
  Foot Rot Diphtheria Metritis Swine Dysentery
  Erysipelothrix

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Inhibitors of Protein Synthesis

• Macrolides
• Tilmicosin
• Mechanism, Spectrum Distribution Similar to
  Erythromycin
• Formulations Micotil
• Route of Administration SQ
• Withdrawal Times Not approved for use in
  lactating dairy cattle. Meat - 28 days.
• Uses Shipping Fever
• Precautions Cardiac toxicity in humans, dogs,
  pigs

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Inhibitors of Protein Synthesis

• Lincosamides
• Lincocin
• Mechanism, Spectrum Distribution Similar to
  Erythromycin
• Formulations Lincocin, Lincomix
• Route of Administration IM, PO
• Withdrawal Times Slaughter 48 hours (Swine)
• Uses Swine - arthritis, Mycoplasma pneumonia

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Inhibitors of Protein Synthesis

• Lincosamides
• Pirlimycin
• Mechanism, Spectrum Distribution Similar to
  Erythromycin
• Formulations Pirsue
• Route of Administration Intramammary
• Withdrawal Times Milk - 36 hours Meat - 28 days
• Uses Gram positive mastitis pathogens

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Inhibitors of Intermediary Metabolism

• Sulfonamides
• Sulfadimethoxine
• Mechanism Inhibits folic acid synthesis
• Spectrum Gram positive and negative bacteria,
  variable anaerobic activity, coccidia, some other
  protozoa
• Formulations Albon, Albon-SR
• Route of Administration PO, IV
• Withdrawal Times Albon (Milk - 60 hours Meat -
  7 days) Albon-SR (Not for use in lactating dairy
  cattle Meat - 21 days)
• Distribution Most Tissues including CNS milk
  concentrations less than plasma
• Uses Foot Rot, Pneumonia, Corynebacterium,
  Salmonella

Note Under AMDUCA Only Approved Forms of
Sulfonamides Can Be Used In Lactating Dairy Cattle
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Inhibitors of Nucleic Acid Synthesis

• Fluroquinolones
• Enrofloxacin
• Mechanism Inhibits DNA gyrase enzyme
• Spectrum Gram positive and negative bacteria,
  Brucella, Chlamydia, Mycoplasma, Mycobacterium
• Formulations Baytril-100
• Distribution Lipid soluble, intracellular
  penetration, not well distributed in CNS
  Post-antibiotic effect.
• Withdrawal Times Not for use in lactating or
  preruminant dairy calves Meat - 28 days.
• Uses Only approved livestock use is for the
  treatment of pneumonia in cattle. Labeled for
  Pasteurella haemolytica, P. multocida, and
  Haemophilus somnus ONLY.

Note Extra-label Use of Fluroquinolones in Food
Producing Animals is Strictly Prohibited.
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Antimicrobial Resistance

• Three areas of concern
• Intestinal Infections - reservoir of R-factors
  may be carried by commensal bacteria in the gut
• The use of low levels of antibiotics (e.g., feed
  additives, or improper dosing) may lead to a high
  occurrence of R-factors in the bacterial
  population
• Indiscriminate use of antibiotics ? eliminate
  effectiveness of antimicrobial substances in
  future

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Principles of Rational Antimicrobial Therapy

• Know your patient
• Know the infection
• Viruses dont respond to antibiotics
• Location - tissue perfusion, etc.
• Culture and Sensitivity (Bacteria)
• Remove the pathogen or source if possible
• Select an appropriate antimicrobial agent and
  dose regimen
• Dose adequately
• Maintain the dosage
• Monitor treatment outcome
• Record keeping
• Investigate therapeutic failures
• Recognize and address adverse drug reactions

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Other Commonly Used Therapeutics
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Anti-Inflammatories

• Glucocorticoids
• Azium - Dexamethasone
• Mechanism Inhibits Phospholipase thereby
  blocking the arachidonic acid cascade
• Activity Anti-inflammatory, abortifacient,
  stabilization of cell membranes, gluconeogenic
• Route of Administration IV, IM
• Clinical Uses Treatment of edema, insect
  bites/stings, nerve injury, ketosis, and aseptic
  laminitis. Termination of pregnancy.
• Side effects Abortion, adrenal suppression,
  muscle catabolism, immunosuppression.
• Withdrawal Time None

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Anti-Inflammatories

• Non-Steroidal Anti-Inflammatory Agents (NSAIDs)
• Banamine - Flunixin Meglumine
• Mechanism Inhibit cyclooxygenase
• Activity Analgesia, anti-inflammatory,
  antipyrexic
• Route of Administration IV, IM
• Label Approved Use Control of pyrexia (fever)
  associated with bovine respiratory disease and
  endotoxemia and for control of inflammation
  associated with endotoxemia.
• Withdrawal Time Meat - 4 days Not for use in
  lactating dairy cattle

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Arachidonic Acid Cascade
Membrane Phospholipid
Glucocorticoids
Phospholipase
Arachidonic Acid
Cyclooxygenase
Lipoxygenase
NSAIDs
Leukotrienes
Prostaglandins
Thromboxanes
Prostacyclins
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Mechanisms of Edema

• Increased Vascular Permeability
• Decreased Plasma Colloid Oncotic Pressure
• Increased Hydrostatic Pressure
• Decreased Lymphatic Drainage

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Diuretics

• Loop Diuretics
• Lasix - Furosemide
• Mechanism Inhibition of NaK2Cl carrier in
  thick ascending loop of Henle.
• Activity Diuresis (Fluid loss by kidney)
• Route of Administration IV, PO
• Clinical Uses Treatment of udder edema Label -
  treatment not to exceed 48 hours post-partum.
• Side Effects Potassium and Ca2 wasting,
  dehydration
• Withdrawal Time Milk and Meat 48 hours

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Diuretics

• Thiazide/Glucocorticoid Combination
• Naquasone - Trichlormethiazide, Dexamethasone
• Mechanism Naqua - Inhibition of Na and Cl
  reabsorption by renal tubules Azium - see prior
  slide.
• Activity Stabilize vascular membranes, decrease
  inflammation and induce diuresis. Ca2 sparing.
• Clinical Use Udder edema
• Withdrawal Time Milk - 72 hours
• Side Effects Abortion

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Miscellaneous Therapeutics

• Reproductive Drugs
• Reproduction Section
• Parasiticides
• Parasite Section
• Sedatives, Anesthetics and Tranquilizers
• Briefly covered under surgical diseases of cattle
• Growth Promoting Hormones
• Fluid Therapy
• Briefly covered under neonatal disorders

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References

• http//www.bqa.org
• http//www.dqacenter.org
• Principles of Antimicrobial Therapy, VM 532P,
  Veterinary Pharmacology and Toxicology, Debra
  Sellon, DVM, Ph.D., Washington State University
• Plumb DC. 1999. Veterinary Drug Handbook, 3rd
  Edition. Iowa State University Press.
• Compendium of Veterinary Products. 1999. North
  American Compendiums Inc., Port Huron, MI.

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Results Exam 1
Mean 80 Median 82 SD 9.9