HUMAN PAPILLOMA VIRUS (HPV)

HUMAN PAPILLOMA VIRUS (HPV)
By: Nathalia Cruz

What is a Virus?
* Exceptionally simple living microbes.
* Contain a single type of nucleic acid (DNA or RNA) and a protein coat.
* Obligatory intracellular parasites.
* Range from 20 to 14.000 nm in length.
* It’s classification is based on type of nucleic acid, strategy for replication, and morphology

HUMAN PAPILLOMA VIRUS
* HPV is the virus that causes warts.
* More than 100 different kinds, 30-some of this cause genital HPV.
* Spread by sexual contact or from mother to baby.
* Genital warts appear 6 weeks to 8 months after contact with an HPV infected person.
* The most common sexually transmitted disease worldwide.
* Certain types of HPV are linked with cervical cancer.
* Divided into 2 subcategories: Genital Warts and Cervical Dysplasia.
* Most people do not know they have it.
* There are high risk and low risk types of it.

HISTORY
* The papillomaviruses are part of the PAPOVAVIRIDAE family of DNA tumor viruses.
* First discovered in the early 40’s.
* Gained notoriety in the early 80’s when it was discovered that some types of HPV caused cervical cancer.

MORPHOLOGY
* Papilloma virus genome is circular covalently closed double stranded DNA of about 8 kbp.
* All PV genes are coded in one of the 2 DNA strands utilizing the alternative splicing for the individual expression of each gene.
* Papillomavirus expression is characterized by a large array of mRNAs cells coding for different genes.
* 55 nm in diameter.

MECHANISM OF INFECTION
* All PV exhibit extreme specificity for infection on epithelial cells.
* The papillomavirus epitheliotrophy resides in the interaction of specific transmission factors with the viral regulatory region LCR.
* The infection normally results in hyperproliferation of the host cell and may lead to transformation and immortalization.

GENITAL WARTS
* Sometimes called condylomata acuminata.
* Are soft, moist or flesh colored, and appear in the genital area within weeks or months after infection.
* Sometimes appear in clusters and are either raised or flat, small or large.
* Women: appear in the vulva, cervix, vagina and anus.
* Men: Can appear on the scrotum or penis.

LIFE CYCLE (HPV-16)
* Starts with the infection of the host cell.
* The virus DNA is released within the nucleus
* Numerous cellular transcription factors interact with the non-coding viral regulatory region (LCR), starting transcription of the two hpv-16 transforming early genes (E6 and E7).
* The transforming proteins interact with the cellular antioncogenic regulator p53 disrupting the cell cycle.

HPV TYPES
* Numbered in order of discovery.
* 30 HPV types primarily infect the squamous epithelium of the lower anogenital tracts of both males and females.
* HPV types 6, 11, 42, 43, or 44 present as papillary condylomas, may also present as flat lesions that may or may not be visible to the unaided eye are part of the “low-risk” HPV types.
* Types 16, 18, 31, 33, 35, 45, 51, 52, and 56 are considered “high-risk” types because they have been found in cervical and other lower genital tract cancers.

HPV GENOMIC ORGANIZATION
* Three main regions (early, late and the long control region)
* (E) resides the transformation and immortalization potential.
* (L) Two capsid genes.
* (LCR) contains all the cis-regulatory elements.

HOW HPV CAUSES CANCER
* HPV DNA integrates into the host genome.
* The proteins E6 and E7 are produced from the resultant DNA.
* E6 binds and degrades p53 (a tumor suppressor gene).
* If the DNA is altered, the cell keeps replicating. The mutation rate of the cell increases.
* E7 binds and degrades retinoblastoma (another tumor suppressor gene).
* Retinoblastoma normally keeps the cell from growing too fast or responding to growth stimulators. This inhibitory factor is now lost.
* without these two mechanisms to slow down cell growth and prevent mutation. . .
* Malignant Transformation Occurs.

HPV TREATMENT
* Genital warts can be treated by a doctor and by different methods.
* Podofilox gel: A patient-applied treatment for external genital warts.
* Imiquimod cream: A patient-applied treatment.
* Chemical treatments (including trichloracetic acid and podophyllin), which must be applied by a trained health care provider to destroy warts.
* Cryotherapy: Uses liquid nitrogen to freeze off the warts.
* Laser therapy: Uses a laser beam or intense lights to destroy the warts.
* Electrosurgery: Uses and electric current to burn off the warts.
* Surgery: Can cut away the wart in one office visit .
* Interferon: an antiviral drug, which can be injected directly into warts.

CURE
* There is currently no cure for human papillomavirus.
* Once an individual is infected, he or she carries the virus for life even if genital warts are removed.
* The development of a vaccine against HPV is under way, but is still not available.
* If left untreated, some genital warts may regress on their own.

HUMAN PAPILLOMA VIRUS.ppt

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Protect yourself and Protect others! During this Flu Season

Protect yourself and Protect others!
During this Flu Season…

This module has been designed to provide information to the Duke Employees on seasonal and H1N1 Flu. After completing this module, you will be able to:

* Identify important facts related to seasonal and H1N1 Flu
* Describe proper hygiene practices and control measures, including vaccination to prevent
o Seasonal Flu and
o H1N1 Flu

* Describe the impact of the seasonal flu and H1N1Flu on employees and on Duke as an organization

Why Should I Be Concerned?

+ Typically, the” Flu” comes around yearly during the fall and early winter. This is considered the “seasonal” Flu and a vaccine is developed each year to provide protection against the most common strains that are expected to cause the most illness.
* Seasonal Flu is a serious disease. In fact, 25,000 to 35,000 die annually in the U.S. due to the seasonal Flu. Those at the highest risk for developing complications are:
o The elderly
o The very young
o Those with chronic medical conditions, such as heart disease, lung disease, diabetes or conditions that effect the immune system

Why Is This Year’s Flu Season Different?

+ This year, there is a new and very different Flu virus spreading worldwide called the H1N1 Flu or formerly known as the “Swine Flu”. Though this new type of Flu is turning out to be milder than originally feared, it can lead to complications.
+ At this time, many are susceptible to the H1N1 and those infected experience symptoms similar to the seasonal Flu. Those at highest risk for complications seem to be:
# Pregnant women
# Children
# Youth and young adults up to age 24
# Those with chronic medical conditions between ages 24 and 64

What Does This Mean For DU/DUHS?

Based on the government’s current estimate, 30-50% of our employees could be infected with the Flu this season.

Since we work closely together in the Duke community, we have many opportunities for contact.

Duke is taking steps to slow the spread of illness in the workforce.

Protecting yourself, your co-workers and your patients is the best way to decrease the impact of either the seasonal Flu or the H1N1 Flu. You’ll find out how in the next slides.


Remember that we all are susceptible to BOTH kinds of Flu.

To Protect Yourself & Prevent Spread . . .

It is important to know that the Flu is highly contagious, and spreads when the virus is passed from one individual to another individual. This can happen when an infected individual:

o Coughs, sneezes, or has direct physical contact with another individual
o Indirectly contaminates objects such as door knobs, telephones or surfaces. This is not the most common route of infection.

Remember that the virus can spread from the hands to eyes, nose, and mouth; so good hand hygiene is critical.

Here’s What You Can Do To Prevent Spreading The Virus . . .

+ Wash your hands. Washing hands often with soap and water or an alcohol-based hand cleaner will help protect against germs.
+ Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash immediately after use. Wash your hands immediately.
+ If a tissue is not available, cough or sneeze into your elbow or sleeve.
+ Avoid touching eyes, nose or mouth. Germs are often spread when you touch something contaminated with germs and then touch your eyes, nose or mouth.
+ Stay home and away from others when you’re sick. You will help prevent others from getting sick.

And Take The Time To Get Vaccinated

* Too many employees unwisely continue to work while sick with the Flu.
* Unvaccinated workers who are not yet feeling sick can spread the virus.
* Infected individuals may be infectious the day before they become sick as well as after their fever is gone.

YOU maybe the source of Flu transmission!

Get Vaccinated for Seasonal Flu
The Center for Disease Control recommends a seasonal flu vaccine as the first and foremost important step in protecting against seasonal flu. Vaccination for seasonal Flu is vital for:

* Individuals at high-risk for serious Flu complications:
o The elderly
o The very young
o Those with chronic medical conditions, such as heart disease, lung disease, diabetes or conditions that effect the immune system
* Health care workers
* Individuals who live with or care for high-risk individuals
* All persons wishing to prevent seasonal flu


For more information, go to www.cdc.gov
Remember That DU/DUHS Offers Free
Seasonal Flu Vaccination

* Duke offers free seasonal flu vaccination to all employees.
* Times and locations of flu vaccination sites will be posted online at www.duke.edu/flu.
* Bring your Duke ID to receive the vaccination.
* If you have a fever, postpone your flu shot.

And Remember To Get Vaccinated for H1N1

* The seasonal Flu vaccine will not protect you against the H1N1 Flu.
* A separate vaccine is being developed for H1N1. It is expected to be available in late fall.
* The H1N1 vaccine will be distributed based on criteria as defined by the Centers for Disease Control (CDC).

How Do I Know If I Have The Flu?

Symptoms for both the Seasonal Flu and H1N1 Flu are similar . . .

o Fever of 100 degrees or more and any of these symptoms:
+ Cough
+ Sore throat
+ Runny or stuffy nose/sneezing
+ Body ache
+ Headache
+ Chills
+ Unusual fatigue

How Should I Care for Myself?

* Get Extra Rest
* Increase Fluid Intake
* Take Fever Lowering Medication (no aspirin for children)
* If you have severe illness or you are at high risk for flu complications, contact your health care provider or seek medical care.

Seek Urgent Medical Attention If You Experience . . .

Any of these emergency warning signs . . .

* Difficulty breathing or shortness of breath
* Pain or pressure in the chest or abdomen
* Sudden dizziness
* Confusion
* Severe or persistent vomiting

Protect yourself and Protect others!.ppt

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The Cardiovascular Examination

Valvular Heart Disease and the Cardiac Exam
By:Charlotte Bai, M.D.
Internal Medicine Board Review
May 28, 2009

Overview
* Clinical syndromes
* Overview of cardiac murmurs and maneuvers
* Left sided valvular lesions
o Aortic stenosis and sclerosis
o Mitral stenosis
+ Rheumatic fever prophylaxis
o Acute and chronic aortic regurgitation
o Acute and chronic mitral regurgitation
* Right sided valvular lesions
o Tricuspid valve disease
* Prosthetic valves
* Endocarditis prophylaxis
* Questions

General Appearance
* Marfan Syndrome
o Tall, long extremities
o Associated with: aortic root dilitation, MV prolapse
* Acromegaly
o Large stature, coarse facial features, “spade” hands
o Associated with: Cardiac hypertrophy
* Turner Syndrome
o Web neck, hypertelorism, short stature
o Associated with: Aortic coarctation, pulmonary stenosis
* Pickwickian Syndrome
o Severe obesity, somnolence
o Associated with: Pulmonary hypertension
* Fredreich ataxia
o Lurching gait, hammertoe, pes cavus
o Associated with: hypertrophic cardiomyopathy
* Duchenne type muscular dystrophy
o Pseudohypertrophy of the calves
o Cardiomyopathy
* Ankylosing spondylitis
o Straight back syndrome, stiff (“poker”) spine
o Associated with: AI, CHB (rare)
* Lentigines (LEOPARD syndrome)
o Brown skin macules that do not increase with sunlight
o Associated with: HOCM, PS
“Spade” hands in acromegaly
* Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu)
o Small capillary hemangiomas on the face or mouth
o Associated with: Pulmonary arteriovenous fistula
* Lupus
o Butterfly rash on face, Raynaud phenomenon- hands, Livedo reticularis
o Associated with: Verrucous endocarditis, Myocarditis, Pericarditis
* Pheochromocytoma
o Pale diaphoretic skin, neurofibromatosis- café-au-lait spots
o Associated with: Catecholamine-induced secondary dilated CM
* Sarcoidosis
o Cutaneous nodules, erythema nodosum
o Associated with: Secondary cardiomyopathy, heart block
* Tuberous Sclerosis
o Angiofibromas (face; adenoma sebaceum)
o Associated with: Rhabdomyoma
* Myxedema
o Coarse, dry skin, thinning of lateral eyebrows, hoarseness of voice
o Associated with: Pericardial effusion, LV dysfunction

Grading the Intensity of Cardiac Murmurs
* Grade 1
o Murmur heard with stethoscope, but not at first
* Grade 2
o Faint murmur heard with stethoscope on chest wall
* Grade 3
o Murmur hears with stethoscope on chest wall, louder than grade 2 but without a thrill
* Grade 4
o Murmur associated with a thrill
* Grade 5
o Murmur heard with just the rim held against the chest
* Grade 6
o Murmur heard with the stethoscope held away and in from the chest wall

Cardiac Murmurs


* Most mid systolic murmurs of grade 2/6 intensity or less are benign
o Associated with physiologic increases in blood velocity:
+ Pregnancy
+ Elderly
* In contrast, the following murmurs are usually pathologic:
o Systolic murmurs grade 3/6 or greater in intensity
o Continuous murmurs
o Any diastolic murmur

Diagnostic Testing
* ECHOCARDIOGRAM
Aortic Stenosis
Progression of Aortic Sclerosis
* Hemodynamic progression usually slow
o Average rate of increase in aortic jet velocity of 0.3 m/s per year
o Increase in mean transaortic gradient of 7 mmHg
o Decrease in AVA of 0.1 cm2 per year
* Severe AS
o Aortic jet velocity > 4 m/s
o Mean transvalvular pressure gradient > 50 mmHg
o AVA < 1.0 cm2

Pathophysiology of Aortic Stenosis
* Obstruction of LV outflow increases intracavitary systolic pressures and leads to LV pressure overload
* Initial compensatory mechanism is myocardial hypertrophy with preservation of systolic function
* Diastolic function impaired as a consequence of increased wall thickness and abnormal myocardial relaxation
* Increased wall stress and afterload causes eventual decrease in ejection fraction

Pseudostenosis
* Occurs in patients with impaired systolic function and aortic stenosis
o Unable to generate transvalvular gradient
* Careful diagnostic testing with dobutamine infusion protocols can aid in differentiating between true AS and pseudostenosis
* If the calculated AVA increases with augmentation of cardiac output, then pseudostenosis present
* If AVA does not increase with dobutamine, then obstruction fixed and true AS present

Clinical Presentation of Aortic Stenosis
* Cardinal symptoms:
o Angina
+ Occurs in >50% of patients, not sensitive due to prevalence of CAD
o Syncope
o CHF
* Sudden cardiac death rare, <1% per year
* In earlier stages, AS presentation more subtle
o Dyspnea
o Decreased exercise tolerance
* Rarely, AS diagnosed in the setting of GI bleeding
o Heyde’s syndrome
+ Bleeding caused by AVM
+ Concurrent AS occurs at prevalence rate of 15-25%
+ Associated with an acquired von Willebrand syndrome due to disruption of vW multimers through a diseased AV

Management of Aortic Stenosis
* Prognosis in asymptomatic disease excellent
* Conservative approach with monitoring for symptoms recommended
* When severe stenosis present-
o 38% of asymptomatic patients develop symptoms within 2 years
o 79% are symptomatic within 3 years
* Once symptoms occur, AVR needed
* LV dysfunction and severe AS have increased perioperative mortality with AVR
o But outcomes still favorable with surgery
* Nitroprusside may transiently improve cardiac function as a bridge to valve replacement
o Does not supplant AVR in symptomatic patients

Aortic Valve Replacement
* Prophylatic AVR in asymptomatic patients not routinely performed due to surgical risks
o Thromboembolism, bleeding associated with anticoagulation, prosthetic valve dysfunction, and endocarditis
o Occurs at a rate of 2-3% annually
o Only should be considered:
+ If other cardiac surgery (such as CABG) planned
+ Severe LVH or systolic dysfunction
+ Women contemplating pregnancy
+ Patients remote from health care
* Surgical valve replacement with operative morbidity and mortality of 10%
* Percutaneous balloon aortic valvotomy rarely used

Mitral Stenosis
* Usually associated with history of rheumatic fever
* >40% of cases of RHD result in mitral stenosis
o Women affected more than men (2:1)
* Presentation 20-40 years after the initial episode of rheumatic fever
o If infected at a young age, latent period is a few years

Clinical Presentation of Mitral Stenosis
* Significant MS leads to ↑LA pressure and pulm HTN
* Symptoms include dyspnea with ↑ cardiac demand
o Exercise
o Pregnancy
* Survival excellent with asymptomatic or minimally symptomatic patients
o >80% survival at 10 years
* Survival in symptomatic patients much worse
o 10 year survival drops to 15% or lower (if pulm HTN present)
* Findings consistent with severe MS:
o Transvalvular diastolic pressure gradient >10 mmHg
o MVA <1.0 cm2
o Severe pulmonary hypertension (>60 mmHg)

Management of Mitral Stenosis
* Atrial fibrillation
Mitral Valve Repair
* Percutaneous valvotomy
Rheumatic Fever Prophylaxis
* Primary prophylaxis
* Secondary prophylaxis
Acute Aortic Regurgitation
Acute Mitral Regurgitation
Chronic Valvular Regurgitation
Chronic Aortic Regurgitation
Chronic Mitral Regurgitation
Treatment of Chronic Mitral Regurgitation
Timing of Intervention for Left-Sided Valvular Conditions
OTHERWISE
Repeat TTE yearly, repeat clinical evaluation biannually
OTHERWISE
Repeat TTE at least yearly, repeat clinical evaluation at least biannually depending on the severity of the LV dilitiation
OTHERWISE
Clinical evaluation at least annually, depending on the severity of the mitral stenosis
OTHERWISE
Depending on the severity of AS, at least annual clinical evaluation with TTE to monitor for symptom onset
Intervention:
AVR
Chronic Severe MR
Chronic Severe AR
Mitral Stenosis
Aortic Stenosis
Tricuspid Valve Disease
* Tricuspid stenosis is rare
o Associated with rheumatic heart disease
* TR usually occurs secondary to:
o Pulmonary hypertension
o RV chamber enlargement with annular dilatation
o Endocarditis (associated with IV drug use)
o Injury following pacer lead placement
* Other secondary causes: carcinoid, radiation therapy, anorectic drug use, and trauma
* Primary causes: Marfan’s syndrome and congenital disorders such as Ebstein’s anomaly and AV canal malformation
* Echo is diagnostic in most cases
Tricuspid Regurgitation
* Severe tricuspid regurgitation is difficult to treat and carries a poor overall clinical outcome
* Symptoms are manifestations of systemic venous congestion
* Surgical intervention usually considered if other cardiac surgery planned
* Surgical options include valvular annuloplasty or replacement

Prosthetic Valves- Mechanical
* Three types:
o Ball-cage valve
o Single tilting disk valve
o Bileaflet valve
* Durable but require life long anticoagulation
* For operative procedures, warfarin typically is discontinued for 48-72 hours and restarted postop as soon as possible, except for:
o Mechanical mitral prosthesis
o Atrial fibrillation
o Prior thromboembolic events
Ball-cage valve
Single tilting disk valve
Bileaflet valve
Prosthetic Valves- Biological
* Biological Valves
o Composed of autologous or xenograft biological material mounted on stents and a sewing ring
o Warfarin therapy not required due to lower thromboembolic potential
o Valve durability less when compared to mechanical valves
o Newer stentless valves with increased longevity

Anticoagulation Guidelines for Mechanical Valves
Prosthetic Valve Complications
* Common complications include:
o Structural valve deterioration
o Valve thrombosis
o Embolism
o Bleeding
o Endocarditis
* Endocarditis prophylaxis required for patients with all types of prosthetic valves
* Suspect valve dehiscence or dysfunction in:
o Acute CHF in the immediate postop period
o New cardiac symptoms
o Embolic phenomena
o Hemolytic anemia
o New murmurs
* TEE is the diagnostic procedure of choice
* Postop TTE should be done 2-3 months after surgery

Valve Thrombosis
* Incidence with mechanical prosthesis of 2-4 % per year
* Suspect in patients with new murmur, change in cardiopulmonary symptoms, or an embolic event
* Diagnosis based on clinical presentation, TTE/TEE, and fluroscopy
* In small thrombus, treatment with heparin may be adequate
* Optimal treatment for left sided thrombosis is emergency surgery
* Consider thrombolytic therapy for right sided thrombosis or if surgery cannot be performed with left sided disease
Endocarditis Prophylaxis

The Cardiovascular Examination.ppt

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