Movement Disorders

Movement Disorders

* Background
o AKA Extrapyramidal Disorders
o These disorders impair the regulation of voluntary motor activity w/o affecting the strength, sensation, or cerebellar fcn.
o Result from dysfunction of the basal ganglia
+ Caudate
+ Putamen
+ Globus Pallidus
+ Subthalamic Nucleus
+ Substantia Nigra
+ Lentiform Nucleus
# Putamen & Globus Pallidus
+ Corpus Striatum
# Lentiform Nucleus + Caudate Nucleus
* Basal Ganglia Circuitry (Fig 7-1)
o Corticocortical Loop:
Cerebral Cortex
Caudate & Putamen
Internal Segment
Globus Pallidus
Thalamus
* Basal Ganglia Circuitry (Fig 7-1)
o Nigrostriatal Loop:
Substantia Nigra
Caudate & Putamen
* Basal Ganglia Circuitry (Fig 7-1)
o Striatalpallidal Loop:
Caudate & Putamen
External Segment
Globus Pallidus
Subthalamic Nuclei
Internal Segment
Globus Pallidus
* Types of Abnormal Movements
o Tremor: rhythmic movement characterized by when it occurs
+ Postural Tremor
# During sustained posture
+ Intention Tremor
# During movement; absent at rest
+ Resting Tremor
# At rest
o Chorea: irregular muscle jerks
+ Florid Cases
# Fully developed
# Forceful movements of limbs, head, facial grimacing, & tongue movements
+ Mild Cases
# Characterized by:
* Clumsiness
* Milkmaid grasp
* Absent in sleep
o Hemiballismus
+ Unilateral Chorea
+ Involves the proximal muscles
+ Vascular disease of contralateral subthalamic nucleus
o Athetosis
+ Continued slow, sinuous, & writhing movements
o Dystonia: sustained athetotic movements
+ Segmental Dystonia
# Affects one or more limbs
+ Focal Dystonia
# Affects localized muscle groups
+ Palliative/Provocative
+ Causes
o Myoclonus
+ Definition
+ Classification
+ Generalized: widespread
# Physiological
# Essential
# Epileptic
# Symptomatic
+ Segmental: more localized
o Tics
+ Definition
+ Palliative/Provocative
+ Types
# Transient Simple: common in children, resolve w/I 1 yr
# Chronic: any age, no tx
# Persistent Simple or Multiple: onset before 15 yoa, resolve in adults
# Chronic Multiple: Tourette’s Sydrome
* Hypokinetic Movement Disorders
o Parkinson’s Disease
* Hyperkinetic Movement Disorders
o Huntington’s Disease
o Wilson’s Disease
o Tourette’s Syndrome
o Restless Leg Syndrome
* Parkinson’s Disease - Hypokinetic
o Defined as a syndrome consisting of variable combination of tremor, rigidity, bradykinesia, and characteristic disturbance of gait and posture
o Onset: mid-late life; mean age is 57 yrs
o Epidemiology:
+ Affects all ethnicities
+ has equal M/F distribution
+ occurs 1-2 per 1,000 people in general population
+ occurs 1 per 100 people that are over 65 yrs
+ 4th most common disease in the elderly
* Parkinson’s Disease - Hypokinetic
o Cause: unknown
o Pathophysiology:
+ Loss of dopaminergic cells in the substantia nigra
# Dopamine’s normal function
+ Over excitation of the caudate & putamen
+ Over excitation of the corticospinal tracts
+ Oscilation of feedback
+ Decrease in thalamic excitation of the motor cortex
o Four Hallmark Signs
+ Resting Tremor (Pill-Rolling)
+ Rigidity (Lead-Pipe or Cogwheel)
+ Bradykinesia
+ Flexed Posture with shuffling gait (Festinating)
o Examination:
+ History
+ Phsyical Findings:
# Passive movement
# Muscle Strength
# Sensory
# Deep Tendon Reflexes
# Autonomic
# Myerson’s Sign
# Pull Test
o Diagnosis:
+ Four Hallmark signs
+ Tremor is absent in 30% of patients
o Differential Diagnosis
+ Involuntary tremor vs. Intentional tremor
+ Depression
+ Wilson’s Disease
+ Huntington’s Disease
o A neurodegenerative disorder which predominately has behavioral, cognitive, or signs
o Onset: Usually begins during adult life
o Epidemiology:
+ 5-10 per 100,000 in the US
+ 50% chance to pass on the disorder
+ Anticipation
+ Paternal Descent
* Huntington’s Disease – Hyperkinetic
o Cause: Autosomal Dominant Disorder
o Pathophysiology:
+ Mutation on chromosome 4: CAG repeats
+ CAG Normal Function: codes for glutamine
+ Over-expression of the gene: i.e. excess glutamine
+ Uncertainty?
* Huntington’s Disease – Hyperkinetic
o Cause: Autosomal Dominant Disorder
o Pathophysiology:
+ Pathological Changes
# Atrophy & neuronal degeneration of cortex
# Hallmark: caudate atrophy
+ Projected Conclusion?
# Over activity
# Under activity
o Examination:
+ Physical Findings
# Initial Findings
* Gradual onset
* Slowed saccadic movements 1st sign
* In 85% chorea is predominate movement disorder
# Juvenile Form
* AKA The Westphal Variant
* Rigidity & bradykinesia
* Tremors, Dystonic postures, & Ataxia
* Mental retardation, Seizures, & myoclonus
o Examination:
+ Physical Findings
# Adult Onset
* Prominent chorea
* Bradykinesia
* Postural reflex compromise
# Terminal Phase
* Dysarthria, dysphagia, & respiratory difficulties
# General
* Cognitive impairment
* Depression
* Psychiatric disorders
* Wilson’s Disease – Hyperkinetic
o Onset
+ Hepatic Dysfunction – 11 yoa
+ Neurological Dysfunction – 19 yoa
o Epidemiology
+ Rare
+ 1 in 40,000 people
o Cause: Autosomal Recessive Disorder
o Pathophysiology
+ Abnormal copper metabolism
+ Deposition of copper in tissues
o Examination
+ Physical Findings
# Children: hepatic dysfunction predominates
* Sardonic Smile
* Behavioral problems
# Adults: neurological dysfunction predominates
* Parkinsonian features
# General
* Hallmark: Kayser-Fleischer Rings
* 1/3 experience psychiatric symptoms
* Other ocular abnormalities
* Gilles de la Tourette Syndrome – Hyperkinetic
o Diagnosed when childhood onset tics are multifocal, motor or vocal, lasting longer than 1 yr and naturally wax and wane
o Cause: unknown
o Onset: 2-21 yoa
o Male predilection
* Gilles de la Tourette Syndrome – Hyperkinetic
o Examination
+ Physical Findings
# Simple Tics
* Motor: blinking, facial grimacing, shoulder shrugging
* Vocal: throat clearing, grunting, snorting, barking
# Complex Tics
* Motor: hopping, skipping, Echopraxia
* Vocal: Coprolalia, Echolalia, Palilalia
* Restless Legs Syndrome – Hyperkinetic
o Common movement disorder
o Diagnostic Criteria
# Desire to move limbs which is associated with unpleasant sensations
# Restlessness
# Worsening of symptoms @ rest w/ temporary relief w/ movement
# Worsening of symptoms @ night
* Restless Legs Syndrome – Hyperkinetic
o Common Descriptions
+ Always unpleasant, but not necessarily painful
+ Need to move
+ Crawling
+ Tingling
+ Itching
+ Restless

Movement Disorders.ppt

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Placebo Control: What is it? Why do we use it? Is it ethical?

Placebo Control: What is it? Why do we use it? Is it ethical?
By:Tom Talbot, MD MPH
Vanderbilt School of Medicine

Placebo
* Placebo = “I shall please”
* Pharmocologically inert substances used to satisfy patients that something being done for them (“please the patient”)
* “Any therapeutic procedure (or that component of any therapeutic procedure) which is given deliberately to have an effect, or unknowingly has an effect on a patient, symptom, syndrome, or disease, but which is objectively without specific activity for the condition being treated. The therapeutic procedure may be given with or without the conscious knowledge that the procedure is a placebo, may be an active (non-inert) or inactive (inert) procedure, and includes, therefore, all medical procedures no matter how specific – oral and parenteral medications, topical preparations, inhalants, and mechanical, surgical, and psycho-therapeutic procedures. The placebo must be differentiated from the placebo effect which may or may not occur and which may be favorable or unfavorable. The placebo effect is defined as the changes produced by placebos. The placebo is also used to describe an adequate control in research.” -- Shapiro

Placebo: Why Use it?
* Need to control for therapeutic aspects of prescribing a medication or procedure not directly due to the medication or procedure itself
* i.e. . . . The Placebo Effect

Placebo: History
* First placebo-controlled trial:
o Sanocrysin vs. distilled water to treat TB
o 1931
The Story of Kebrozion
* Pt. with lymphosarcoma
* Patient given Kebrozion
* “The tumor masses had melted like snowballs on a hot stove, and in only a few days, they were half their original size!”
* 2 months later – Kebrozion outed
* Pt given a “new form” of Kebrozion
* Water injections
* Tumors resolved remission
* 2 months later: AMA – “This stuff’s worthless”
* Pt. returns in extremis and dies

Kebrozion, Pt 2
Issues
* Does use of placebo remove access to effective standard of care?
* Is a trial that does not use placebo arm scientifically rigorous?
* Does use of a placebo sacrifice ethics and an individual patient’s welfare?

Placebo-Control: PROS
* Need placebo control to insure validity
Placebo-Control: PROS
* Need placebo control to insure validity
* Argue that no drug should be approved for patient use if it is not clearly superior to placebo or no treatment
* Scientifically invalid research is itself unethical
* Harm and discomfort nonexistent or small in some cases

Placebo-Control: PROS
* Places patients at less risk of harm due to need for smaller numbers for placebo-controlled trials
o Greater power with smaller numbers than noninferiority trial
o Many more exposed to drug in non- placebo trial
* FDA:
o Placebo controls required for disorders of moderate severity and pain
o Beta-blocker not approved for angina (even though it was shown to be as efficacious as proven tx) due to lack of placebo comparison
* Unethical to withhold effective treatment
* Places demands of science ahead of right and well-being of patients
* Your study question has to change:
o Is the new drug better than proven effective therapy?

Placebo-Control: CONS
* Patients are owed medical care for ailments when they present to healthcare providers
* Not truly testing therapy against “no treatment” placebo effect
Rothman KJ et al NEJM 1994;331:394 Enserink M Science 2000;490:418-9
* Declaration of Helsinki:
o “Every patient -- including those of a control group, if any -- should be assured of the best proven diagnostic and therapeutic method.”
o 2000 Revision: Placebos may be used only when there are no other therapies available for comparison with a test procedure
* “Concedes to individual investigators and to IRBs the right to determine how much discomfort or temporary disability patients should endure for the purpose of research”
Clinician/Physician Clinical Researcher
Ethical?
* Subjects: Cancer patients
* Intervention: Odansetron vs. placebo
* Indication: Post-chemotherapy emesis and nausea
* ? Proven effective therapy for nausea
* Subjects: Men with hair loss
* Intervention: Compound X vs. placebo
* Indication: Prevent hair loss
* ? Lack of sequelae from placebo use
* Subjects: Pts. with depression
* Intervention: Compound X vs. placebo
* Indication: Reduction in depressive sx.
* ? Places placebo pts. at risk for severe sequelae of depression

Ethical Balance
* Valid research vs. Undue harm
Validity Minimize Risk
Ethical Balance Validity
Minimize Risk
* Valid research vs. Undue harm
Placebo-Control and Procedures/Surgery
“A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee”
* Randomized, PLACEBO-controlled trial
* Endpoint: Pain in study knee
* Placebo:
o Did not receive general anesthesia
o Knee prepped, draped
o Three 1cm incisions made
o Knee manipulated as if arthroscopy performed
o No instruments entered the incisions
Placebo-Control and Procedures/Surgery
* Informed Consent:
o Explained study thoroughly
o Subjects had to write the following:
+ “On entering this study, I realize that I may receive only placebo surgery. I further realize that this means that I will not have surgery on my knee joint. This placebo surgery will not benefit my knee arthritis.”
o 44% declined
So . . . What do you think? Is this ethical?
Placebo-Control and Procedures/Surgery
* Placebo is not necessarily without risk
* Placebo surgery “violates an essential standard for research: the requirement to minimize the risk of harm to subjects.”
* Again – is there harm in performing an unvalidated procedure?
* Does the risk exceed that of other research procedures from which the subject does not receive benefit?
o Bronchoscopy in healthy adults
o Placement of P-A catheter in non-critically- ill subjects
o Muscle biopsy in healthy adults
* Must be informed
* Must be told that misleading tactics may be used
* Must not be misled about the chances of receiving the sham procedure
* Must be debriefed after study complete and unblinded
* Arthroscopy Study Results:
o No difference in pain scores
o The surgery itself had been causing undue risk (and cost – $3.25 billion/year)
o Without the placebo-controlled study, this would never had been discovered

Cultural Issues and Placebo-Control
* What about when conducting research in other countries?
* “Standard of care” is different due to:
o Access to meds
o Access to healthcare
o Basic infrastructure issues
o Cultural beliefs
* Prevention of fetal-maternal transmission of HIV
* Population: African women
* Intervention: Short course AZT vs. placebo
* Problem: AZT shown effective (longer course)
* Critics: Withheld effective, morbidity-reducing treatment
* Supporters: “Standard of care” in the country was no meds – no money or availability

Cultural Issues and Placebo-Control – Ethical?
* Generally felt that the cultural “standard of care” for studies in developing countries should be that of the investigator’s host country

THE USE OF PLACEBO
Placebo Acceptable If . . .
* Use of placebo does not impair health or cause “severe” discomfort
* Existing therapies only partly effective or have very serious side effects
* Low frequency of condition – would prevent enrollment for a larger trial
* Participants at risk of harm from nonresponse are excluded
* Placebo period is a limited to minimum required
* Careful monitoring is insured
* Explicit withdrawal criteria for AE
* Informed consent explicit as to why placebo should be used
* Improved survival or prevention of irreversible morbidity does not exist for any therapy
Questions

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MRI Safety and Policies & Procedures

MRI Safety and Policies & Procedures

Magnet Safety at ALL TIMES
Outline
Understanding Magnets
o Your role in MR Safety
o Metallic Screening
o Screening Patients / Colleagues
o Other Safety Considerations

What to do in Emergencies
MRI Department Policies and Procedures
Preview MRI Safety Videotape

Magnetism / Magnets
* All substances possess some form of magnetism.
* The degree of magnetism exhibited depends on the atoms that make-up the substance.
* Magnetic susceptibility is the ability of a substance to become magnetized.
* Ferromagnetic substances, such as iron have a large magnetic susceptibility, it is easily magnetized permanently and becomes a magnet itself.
* All magnets have a North and a South pole.
* All magnets have a “fringe” magnetic field which exists in the vicinity surrounding the magnet.

Magnetic Fringe Fields
* The fringe magnetic field is the magnetic field which exists in the vicinity surrounding the magnet.
* This field may extend many meters from the magnet itself.
* These imaginary lines of force demonstrate the pattern of the magnetic field.
* Safety and operational concerns make it necessary to contain the fringe field to a small area.
* Magnetic fields are measured in units of Gauss or Tesla.

MRI Safety at ALL TIMES
A STATIC MAGNETIC FIELD IS ALWAYS PRESENT 24hrs/day, 365 days/yr. EVEN WHEN NOT IN USE.
ANY PERSON USING THE MAGNET MUST BE CERTIFIED AFTER ATTENDING THE MRI SAFETY TRAINING CLASS.
ONE MUST BE TRAINED ON THE SCANNER INTERFACE BEFORE SCANNING.

What is your role in MR Safety?
The greatest risk of injury and damage to the system results from:
o Misuse or abuse of the MR equipment
o Failure to comply with recommended safety procedures
o Lack of proper inspection and maintenance of the MR equipment

Who should know MR Safety?
All in-house personnel that have reason to enter the MR suite area should be trained in MR safety procedures:
o MR technologists, students, researchers, transporters and other medical personnel
o Maintenance and janitorial personnel
All personnel must be thoroughly briefed about the potential risks involved and reminded not to bring any ferromagnetic items into the magnetic field.

Examples of items in-house personnel may have that can become projectiles if brought into the magnetic field

Tool Kits
Clipboards, Metal Pens
Tools
Gurneys, Wheelchairs
Vacuum Cleaners
Oxygen Cylinders
Buffers
Stethoscopes
Buckets
Scalpels, Syringes, Needles
Dustpans
Scissors, Hemostats
Maintenance & Janitorial personnel
MR technologists, students, researchers, transporters & other medical personnel

Who should know MR Safety?
Public safety forces that may respond to the MR suite for an emergency must also know the potential hazards of the MR equipment.
o Law enforcement personnel
o Fire department personnel

A person from the MR site should discuss the possible hazards with these people and provide them with handouts that will reinforce the information.

Examples of items public safety forces may have that can become projectiles if brought into the magnetic field
Breathing apparatus
Fire Extinguishers
Flashlights
Pike poles
Clipboards
Nozzles
Handcuffs
Hose couplings
Knives
Axes
Guns
Fire Department personnel
Law enforcement personnel

MRI Safety - Projectiles
* Projectile effects of metal objects seriously compromise safety. The potential harm cannot be over emphasized.
* Many types of clinical equipment are ferromagnetic and should never be brought into the scan room.
* Items may be tested for magnetic susceptibility with a hand-held magnet located at each MR station.

Metal Objects Becoming Projectiles
Fatal Accidents CAN Happen!
Patient Emergencies
Should a condition exist where the patient is having a medical emergency, all efforts must be made to quickly and safely remove the patient from the scan room.
Once the patient is removed from the MR scan room, close the door to prevent re-entry.
Under no circumstances should a “code team” be allowed to enter the scan room without proper screening!
Controlled Access Area
Although not detectable by the human senses, a magnetic field can be dangerous to equipment and to people.
Since a magnet is always “at field,” safety procedures must be followed to prevent accidents.
For the safety of patients and personnel, controlled access areas are established.

Controlled Access Area
* These areas are established for the safety of patients and personnel.
* The area is labeled with the use of warning signs and markings to prevent the entry of ferromagnetic objects into the controlled access area and to limit the access of individuals with medical implants near high magnetic fields.
* Public access begins at the 5 gauss line (0.5mT).

Equipment / Personal Items
The magnetic field can seriously damage or impair the operation of equipment or personal items such as:
o Oscilloscopes (slow moving electron beams)
o Camera
o Watches
o Credit / Bank cards
o Hearing Aids
o Hair Accessories, Belt Buckles, Shoes

Screening Procedures
* At least one MR operator must screen the patient for possible contraindications that could affect the MR scan. See Patient History and Safety Screening form.
* Check implanted devices in the Reference Manual for Magnetic Resonance Safety by Frank Shellock, Ph.D. or by using MRIsafety.com
Example of MRI Metal Screening Sheet
Screening Procedures
Static magnetic fields can alter the operation of electrically and mechanically operated implants and must remain outside the 5 gauss line.
Pregnant medical personnel should take precautions and remain outside of the magnet room during scanning.
Questions about implants not found in reference material should be discussed with a licensed, MRI technologist or a radiologist before allowing the patient to be scanned.
Absolute Contraindications
* Cardiac Pacemakers (except in rare, controlled environments)
* Cochlear (inner ear) implants
* Swan-Ganz catheters with thermodilution tips
* Ferromagnetic or unidentifiable aneurysm clips of the brain
* Implanted neuro stimulators
* Metal or unidentifiable foreign bodies in the eyes
* Shrapnel near a vital organ
Bioeffects
There is no conclusive evidence for irreversible or harmful bioeffects in humans below 3.0T.
Reversible abnormalities may include but are not limited to:
o Localized tissue and core body temperature heating
o Cutaneous sensations (tingling)
o Peripheral nerve stimulation (involuntary muscle contractions)
o Burn hazards
* Burn Hazards are caused by damaged hardware or by electrical currents produced in conductive loops of material.
* Localized heating is caused by RF irradiation energy absorption to a volume of tissue.
* Dissipation of the absorbed RF energy is described in terms of Specific Absorption Rate (SAR), measured in watts/kg.
* SAR is calculated by the patient’s weight and the expected increase in body temperature for each imaging pulse sequence.
* Patients with poor thermo-regulatory systems must be carefully monitored.
Acoustic Noise
The MR scanner can produce very high acoustic noise levels.
Some patients may experience discomfort from the associated noise of the scanner.
Prior to scanning, it is strongly recommended that earplugs be provided to the patient to reduce the noise level by at least 25dB.

Operating Safely
When operating the MR equipment, be attentive to the following abnormal conditions:
* Louder-than-normal motor noises
* Sparks
* Components overheating
* Smoke or odors coming from the electronic equipment or from within the scan room.
Do not operate equipment with protective panels opened or removed, there is risk of electric shock and can cause image artifacts.

Magnetic Field / Scan Room Emergencies
If an emergency situation arises, you may need to quickly bring down the patient systems and remove power from the MR system.
The nature of the emergency will dictate which procedure you follow. Each procedure has a distinct and specific purpose.
Each magnet is equipped with two emergency buttons:
* Emergency Stop / Shut Off
o Turns off all incoming electrical power to the magnet Power Distribution Unit (PDU)
* Quench or Emergency Run Down
o Causes immediate collapse of the superconductive magnetic field within minutes

FAMILIARIZE YOURSELF WITH THESE BUTTONS. KNOW THE DIFFERENCE!
Emergency Stop / Shut Off Button
Shutting power to the PDU may be required for life threatening situations such as:
* Fire in the computer room
* Fire, sparks, loud noises emanating from the scan room
* Flooding or sprinkling system goes off
* Catastrophic equipment failure
***Keep in mind that when this button is pushed, it does not initiate a quench, the magnet remains “at field.” Exercise caution, make sure that all ferromagnetic materials remain outside of the scan room***
Quench / Emergency Run Down Button
The following situation is THE ONLY TIME that may require quenching of the magnet:
* Large magnetic object pins or impales a person against the magnet and no other method can prevent further injury or free the person.
Do not attempt to pull large magnetic objects (oxygen tanks) from a magnet field. The object may change its magnetic polarity and re-align itself on the magnet and become a projectile, causing a serious or fatal injury.
Do not touch a quenched magnet. Under certain conditions, an electrical potential of >1,000 volts could exist on the surface of the magnet.

Quenching
Definition: a loss of superconductivity of the magnet coil due to a local temperature increase in the magnet as it becomes resistive, resulting in rapid evaporation of liquid helium in the cryostat and quickly reducing the magnetic field strength.
* A quench may happen spontaneously or can be manually instigated in case of an emergency.
* Quenching may cause severe and irreparable damage to the superconducting coils (magnet).
* A magnet quench will result in several days’ downtime, so do not press the button except in a true emergency.
* Do not attempt to test this button!

Emergency Buttons @ MR1 Univ. of Utah Hospital
* QUENCH BUTTON
o Button is located on the east wall (with window).
* E-STOP BUTTON
o Button is located behind the door as you enter the scan room (on the right).
QUENCH
OXYGEN
SENSOR
QUENCH
University of Utah Hospital and Clinics
MRI Department Policies and Procedures
This manual is available at all sites having a MRI scanner. Detail of all departmental situations can be reviewed. The following safety considerations are further highlighted:

Cryogen Safety Oxygen Monitors
Metallic Screening Pregnancy / Nursing
Magnet Quench Medical Emergencies
Magnetic Field / Scan Room Emergencies
Summary
* MRI scanners are powerful magnets with the ability to attract ferromagnetic objects.
* Any personnel around the MRI suite must be adequately screened for metallic implants and personal items before entering the scan room.
* Patients in the scanner must be carefully monitored for reversible bioeffects caused by the magnet’s hardware.
* Become familiarized with E-Stop vs. Quench buttons at each scanner.
* Review Policies and Procedures Manual

Congratulations!
You have completed the University of Utah Hospital and Clinics MRI Safety Training course!
Please review a safety video that demonstrates the powerful forces of MRI magnets.
Following written certification, you will be authorized to aid or assist an MRI technologist with patient examination procedures.

MRI Safety and Policies & Procedures.ppt

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Computers in Medical Education

Computers in Medical Education
Roles of computers in medical education
* Provide facts and information
* Teach strategies for applying knowledge appropriately in medical situations
* Encourage the development of lifelong learning skills

Goals
* Students must learn about physiological processes
* Must understand the relationship between observed illnesses and underlying processes
* Must learn to perform medical procedures
* Must understand the effects of interventions on health outcomes

Basic curriculum
* Premedical requirements
* Medical school
o Basic
+ Physiology
+ Pathophysiology
o Clinical
* Residency
* CME

Teaching strategies
* Lecture
* Interactive

Process
* Presentation of a situation or body of facts containing core knowledge
* Explanation of important concepts and relationships
* How does one derive the concepts
* Why they are important
* Strategy for guiding interaction with the patient

Weaknesses of traditional approach
* Rapid knowledge growth
* Reliance on memorization rather than problem solving
* Reliance on lecture method

Terms
* Computer assisted learning
* Computer based education
* Computer assisted instruction

Advantages of computers in medical education
* Computer can augment, enhance or replace traditional teaching methods
o Rapid access to body of information
+ Data
+ Images
+ Immersive interfaces
o Any time, any place, any pace
o Simulated clinical situation

Advantages
* Interactive learning
o Active vs. passive solving
* Immediate student specific feedback
o Correct vs. incorrect, tailored response
* Tailored instruction
o Focus on areas of weakness
o Request help in interpretation
* Objective testing
o Permits standardized testing
o Self-evaluation
* Fun!

Experimentation
* Safe exploration of what-if in a well done scenario
o You can do things with simulated patients you can’t do with real ones

Case variety
* The ability to experience disease scenarios one otherwise wouldn’t see
o Simple: diabetes
o Complex: multiple disease, multiple medications
Time
* Manage diseases as they evolve over time
o Rapidly evolving problems
o Chronic diseases

Problem-solving competency
* Book smart vs. real-world
* Memorization vs. thinking
* Testing
* Right answer vs. cost-effective vs. safest vs.quickest (fewest steps)

Board examinations
* USMLE test
* CME testing

History of CAI
* Pioneering research in the 1960’s
o Ohio State
+ Tutorial evaluation system
# Constructed choice, T/F, multiple choice, matching or ranking questions
# Immediate response evaluation
# Positive feedback
# Corrective rerouting
+ Authoring language
History
* Barnett MGH 1970
o Simulated patient encounters
+ 30 simulated cases
o Mathematical modeling of physiology
+ Warfarin, insulin, Marshall
o Dxplain
* University of Illinois
o Computer aided simulation of the patient encounter
+ Computer as patient
+ Natural language encounter
* Illinois 1970’s
o Programmed logic for automated teaching (PLATO)
+ Plasma display (required specialized equipment)
+ Combination of text, graphics and photos
o TUTOR authoring language
* University of Wisconsin
o Used simulated case scenarios and estimated the efficiency of the student in arriving at a diagnosis (cost-effectiveness)
* Initial installations site limited
* Subsequent modem dial-up
* Proliferation of medical CAI, CME development entities
* Development of the internet
o Initial material bandwidth limited
o Increasing use of streaming video

Modes of CAI
* Drill and practice
* Didactic
Modes
* Discrimination learning
* Exploration vs. structures interaction
o Hyperlink analogy
o Requires feedback/guidance
* Constrained vs. unconstrained response
o Student may have a pre-selected set of possible response (learn to answer questions)
o Student may be able to probe system using natural language
* Constructive
o Put the body together from pieces of anatomy
Simulation
* Static vs. dynamic
Static simulation
Dynamic simulation
Feedback and guidance
* Feedback
o Correct vs. incorrect
o Summaries
o References
* Guidance
o Tailored feedback
o Hints
o Interactive help
Intelligent tutoring
* Sophisticated systems can
o Intervene if a student goes down an unproductive path
o Gets stuck
o Appears to misunderstand a detail
o Mixed initiative systems
o Coaching vs. tutoring
Graphics and Video
* Storage of images, video etc as part of a multimedia stream
o General appearance
o Skin lesions
o Xrays
o Sounds (cardiology, breath sounds)
Authoring systems
* Generic authoring systems
o McGraw Hill, Boeing
o Simple (constraints) vs. comprehensive (difficult to master)

Examples
* USMLE
* Lister Hill
* Stanford anatomy
* Digital anatomy
* Penn curriculum
* Medical matrix
Continuing medical education
* Echo
* PAC
* CME
Simulators
* ACLS
* Visible human
* Eye simulator
* Other simulators
Future
* Forces for change
* Impediments
o Cost
o Immaturity of authoring tools
o Bandwidth
o Barriers to sharing
+ Institutional jealousy
+ Copyright
* Lack of standard approach
o Authoring software
o Platform
* Explicit integration of CAI into curriculum
* Access to PC’s and LAN

Computers in Medical Education.ppt

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Radiation Safety Oversight of Surgical Procedures

Radiation Safety Oversight of Surgical Procedures Involving the Use of RAM
By: René Michel, M.S., RSO
VA San Diego Healthcare System, San Diego, CA

Introduction
* The objective of this presentation is to review the various Radiation Safety aspects of a typical medical procedure that involves the use of radiological agents.
* Lymphoscintigraphy (LS) is a medical procedure for the treatment of malignant melanoma and mamma-carcinoma.
* The goal is to identify which sentinel lymph nodes (SLN) have been infiltrated by tumor cells
* The objective of this presentation is to determine what basic radiation safety controls are needed.
* ALARA, dosimetry, contamination control, radioactive waste, etc.

Outline
* Radioactive Drugs Used
* Overview of the Procedure
* Radiation Exposure
* Contamination Control
* Recommendations

Radioactive Drugs
* Many radiopharmaceuticals have been evaluated for and used in LS studies
* The ideal drug, must have the following characteristics:
* Small and uniform particle size
* Short half-life
* Low LET
* Appropriate energy for gamma imaging
* 198Au colloid was one of the first widely used drugs in LS
198Au Characteristics
Particle size: 3-5 nm
Half-life: 2.7 d
Emissions: 412 keV photons plus beta particles
* 198Au was replaced by other agents with the increased availability of 99mTc
* Antimony trisulfide, albumin, human serum albumin, sulfur colloid and nano-colloid
99mTc Characteristics
Particle size: 3-90,000 nm
Half-life: 6 h
Emissions: 140 keV photons

Procedure Overview
* There are three stages in Sentinel Node LS
1) Lymphatic Mapping
2) Intradermal Blue Dye Injection
3) SLN Biopsy
Lymphatic Mapping
* The surgeon injects about 1 mCi of 99mTc unfiltered sulfur colloid intradermally near the lesion.
* The colloid is taken up by the lymphatic system and the patient is imaged with a conventional gamma camera.
* About 20 min from injection dynamic scanning is performed
* A late phase scanning done 90 min after injection shows the location of the SLNs.
* The location of the node is marked on the skin of the patient

Blue Dye Injection
* The patient is moved to the OR to perform biopsy
* To assist in identifying the nodes draining the site of interest, a blue dye is injected

SLN Biopsy

* A surgeon uses the skin mark and a scintillation probe to relocalize the highest area of uptake
* A dissection is performed through soft tissue to remove “hot” nodes located by the gamma probe
* All excised nodes are sent to the pathology lab for histological examination to asses for invasion by tumor cells

Radiation Exposure
* Nuclear Medicine personnel are excluded from this evaluation, they are already closely monitored.
* Radiation exposure to OR and Pathology personnel and the potential for spread of contamination are considered the main radiation safety concerns.

Hazards Control-Radiation Exposure
* The expected radiation exposure to personnel from handling SLN radioactive specimens is very small
* 10-15 SLN procedures/year are performed in most large medical centers
* Several studies have documented dosimetry data
Average whole-body radiation dose equivalent/procedure for hospital personnel from malignant melanoma and mamma-carcinoma SLN surgery with typical activities.
* A surgeon's hand dose has been reported to be 10 mrem (Miner et al. 1999)
* The pathologist’s hand dose is even smaller, ~ 4-6 mrem (Veronesi et al.1999)

Hazards Control- Contamination
* The residual activities a day post surgery are <0.3 mCi for tumor-specimens and <50 nCi for SNLE (Kopp and Wengenmair 2002). * These activities are relatively fixed to the tissue, they do not produce contamination that exceeds the allowed levels. * Standard universal precautions used to prevent infections are sufficient to avoid any kind of incorporation in the bodies of those handling specimens. Specimen Control * Under 10 CFR 20.1905 (NRC 2002), labeling is not required for containers holding less than 1.0 mCi of Tc-99m * Labeling is also exempted if only authorized personnel have access to containers, provided a written record identifies the contents. * Specimen quarantine before gross examination is unnecessary since the level of exposure to personnel is not a safety concern. * Despite the simplicity of the guidelines, each institution is expected to develop and implement procedures for handling radioactive specimens. * Awareness training documentation for all individuals handling these specimens is also necessary. Recommended Guidelines 1. Follow standard universal precautions (e.g., wear hospital gown, surgical gloves, etc.). 2. Using forceps, place all radioactive specimens removed from the patient in a sealed container. 3. In addition to the patient’s name and specimen number, label all resected primary site specimens with the name of the isotope (e.g., 99mTc), date and time when it was collected 4. Maintain security of specimens at all times 1. Upon completion of the surgical procedure, all instruments (e.g., forceps, scalpels, etc.) having had direct contact with the radioactive specimens should be cleaned following standard procedures. 2. All specimens should follow the normal biomedical waste stream and be surveyed before disposal to ensure that radiation levels are not distinguished from background References Radiation Safety Oversight of Surgical Procedures.ppt

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Emerging Infections and Medical Procedures

Emerging Infections and Medical Procedures
By:Lennox K. Archibald, MD, PhD, FRCP
Hospital Epidemiologist, University of Florida

Parasitic Infections:
Clinical Manifestations, Diagnosis and Treatment

The Reality
* 1.3 billion persons infected with Ascaris (1: 4 persons on earth)
* 300 million with schistosomiasis
* 100 million new malaria cases/yr
* At UCLA, 38% of pediatric and dental clinic children harbored intestinal parasites

Infections Deaths

Parasites
* Organisms that cannot survive outside their host, AND they cause some harm to the host.
* Contrast with commensal organisms
* Incredibly complex organisms
* Consider the struggle for survival from the perspective of a parasite

Giardia
Giardiasis (G. lamblia)
* Should be suspected in prolonged diarrhea
* Contaminated water often implicated—outbreaks
* Campers who fail to sterilize mountain stream water
* Person-person in day care centers
* MSM
* Symptoms usually resolve spontaneously in 4-6 weeks
* Tests of choice
o Examination of concentrated stools for cysts (90% yield after 3 samples); usually no PMNs
o Stool ELISA, IF Antigen (up to 98% sensitive/90-100% specific)
o Consider aspiration of duodenal contents--trophozoites
* Treatment: Metronidazole for 5-7 days

Entamoeba histolytica
* One of 7 amoebae commonly found in humans
* Only one that causes significant disease
* Causes intestinal disease (diarrhea and dysentery) and extra-intestinal disease (liver primarily)
* In US, often seen in institutionalized patients, MSM, tourists returning from developing countries, patients with depressed cell mediated immunity
Cyst (wet mount)
* Diagnostic smear: trophozoites in liquid stools, cysts in formed stools
* IHA important in liver abscess
o Intestinal: 95% predictive of active infection
o Extra-intestinal: 100% predictive of active I infection

Amoebiasis: Clinical Manifestations
* Symptoms depend on degree of bowel invasion
o Superficial: watery diarrhea and nonspecific GI complaints
o Invasive: gradual onset (1-3 weeks) of abdominal pain, bloody diarrhea, tenesmus
* Fever is seen in minority of patients
* Can be mistaken for ulcerative colitis
* Steroids can dramatically worsen and precipitate toxic megacolon
* Amebic liver abscesses
o RUQ pain, pain referred to right shoulder
o High fever
o Hepatomegaly (50%)

Amoebic abscess—remember…
* Can occur in lung, brain, spleen
* That stool is merely a convenient vehicle passing by
* Amoebae live the bowel wall
* Direct observation preferable to mere examination of stool
* Trophozoites best seen in direct scrapings of ulcers
* Liquifaction of liver cells
* Do not contain pus
* Anchovy paste sauce
* Culture of contents usually sterile
* Liver affected
o 53%--right lobe
o 8%--left lobe

Amoebiasis (Entamoeba histolytica)
Treatment
* Most respond to metronidazole
* Open surgical drainage should be avoided, if at all possible

Cryptosporidium
Cryptosporidium parvum
* Causes secretory diarrhea: 10 liter/day
* Significant cause of death in HIV/AIDS
* Animal reservoirs
* Incubation period: 5-10 days
* Infants and younger children in day-care centers
* Unfiltered or untreated drinking water
* Farming practices: lambing, calving, and muck-spreading
* Sexual practices that brings a person into oral contact with feces of an infected individual
* Nosocomial setting with other infected patients or health-care employees
* Veterinarians: contact with farm animals
* Travelers to areas with untreated water
* Living in densely populated urban areas
* Owners of infected household pets (rare)

Diagnosis and Treatment
* Best diagnosed by stool exam
* There is no known effective treatment-nitazoxamide shortens duration of diarrhea
o Infectious disease specialist - for consideration of antiparasitic and antiretroviral therapy
o Gastroenterologist - ERCP and sphincterotomy; endoscopy sometimes required for diagnosis
o General surgeon - suspected acalculous cholecystitis

Malaria
Falciparum vs. Vivax
* Location: Falciparum confined to tropics and subtropics; vivax more temperate
* Falciparum infects RBC of any age; others like reticulocytes; only 2% infected cells
* Falciparum infected RBCs stick to vascular endothelium causing capillary blockage; fewer schizonts in the periphery, heavy pigment deposition, cerebral and renal disease
* Vivax and Ovale may reinfect hepatocytes, leading to a persisting tissue phase, causing relapses
* Sickle cell trait protects against Falciparum
Malaria: Genetic susceptibility
* Two genetic traits associated with decreased susceptibility to malaria
o Absence of Duffy blood group antigen blocks invasion of Plasmodium vivax
+ Significant number of Africans
o Persons with sickle cell hemoglobin are resistant to P. falciparum
+ Sickle cell disease and trait

Malaria: Clinical manifestations
* Non-specific, flu-like illness
* Incubation
* Fever is the hallmark of malaria
* Fever occurs after the lysis of RBCs and release of merozoites
* Febrile paroxysms have 3 classic stages
* Other symptoms depend upon the strain of malaria
* P. vivax, ovale and malariae: few other sxs
* P. falciparum:
* Always suspect malaria in travelers from developing countries who present with:
o Influenza-like illness
o Jaundice
o Confusion or obtundation

Diagnosis
* Giemsa-stained blood smear
* P. falciparum:
* Others:
* Examine blood on 3-4 successive days
* Key of diagnosis is to identify P. falciparum
* New assays: o ELISA for antigen, immunoassay for LDH, PCR
* Anemia, elevated LDH, increased reticulocytes, thrombocytopenia
* Elevated unconjugated bilirubin without increases in hepatic enzymes
* Elevated serum creatinine, proteinuria, hemoglobinuria, hypoglycemia

Differences in strains
* P. falciparum
* P. vivax and ovale
* P. malariae

Early troph--ring
Mature troph
Schizont
Gametocyte
Treatment
* P. falciparum malaria can be fatal if not promptly diagnosed and treated
* Pts with no immunity against P. falciparum require hospitalization
o Pregnant women, young children, elderly
* Non- P. falciparum malaria rarely requires hospitalization
* Widespread drug resistance dictates regimen (www.cdc.gov/travel; CDC malaria hot line: 770-488-7788).
* Uncomplicated malaria
o Drug options
+ Chloroquine phosphate
+ Mefloquine
+ Quinine sulfate plus doxycycline
+ Atovaquone plus proguanil (AP)
+ Artemisin derivatives
* P. vivax, ovale, malariae, chloroquine-susceptible falciparum
+ Chloroquine
+ Primaquine

Prevention
* Chloroquine
* Mefloquine
* Doxycycline
* Atovaquone plus proguanil (AP)
* Screens, nets
* 30-35% DEET
* permethrin spray for clothing and nets

And don’t forget baggage malaria!
Leishmaniasis
* Tropical areas where phlebotomine sandfly is common:
o South America
o India
o Bangladesh
o Middle East
o East Africa
* Sandfly introduces flagellated promastigote into human ingested by macrophages develops into nonflagellated amastigote
* Intracellular parasite controlled by Th1-type CD8+ response
Leishmaniasis: Clinical Manifestations
* 3 forms: visceral, cutaneous, mucosal
* A single species can produce more than one syndrome, and each syndrome is caused by multiple different species
* Visceral (kala azar)
o Species most prevalent in different places
# L. donovani – India
# L. infantum – Mid East
# L. chagasi – Latin America
# L. amazonensis -- Brazil
* Cutaneous
* Mucosal
Visceral Leishmaniasis
* Dissemination of amastigotes throughout the reticulendothelial system of the body
* Opportunistic infection in AIDS patients
* Ineffective humeral response
Hepatosplenomegaly
Splenic aspirate
* Most satisfactory method
* Spleen must be at least 3cm below LCM
* PT not more than 5 secs longer than controls
* Platelets >40,000
* 21 gauge needle
* Aspirate stained with Giemsa

Leishmaniasis: treatment
* Only drug approved in US is Amphotericin B
* Outside US: pentavalent antimony (sodium stibogluconate)
* Treatment of cutaneous disease depends on anatomic location
* Many spontaneously heal and do not require treatment
* If no mucosal disease and areas of no cosmetic concern:
o 15% paromomycin or 12% methylbenzethonium chloride
* Mucosal, progressive lesions or cosmetically sensitive locations:
o Pentavalent antimony or ketoconazole

Remember..
* The factors determining the form of leishmaniasis:
o Leishmanial species
o Geographic location
o Immune response of the host

Toxoplasmosis
Toxoplasma gondii
* Worldwide distribution
* Human infection
* Prevalence of latent infection in US about 10%; France about 75%
o Generally higher in less-developed world
Transmission
* Eating oocysts excreted by cats harboring sexual stages of parasite
* Outbreaks traced to inadequately cooked meat of herbivores (raw beef)
* Mutton
Toxoplasma gondii: life cycle
Immunocompetent hosts
* Latent infection (persistence of cysts) is generally asymptomatic
* Cervical lymphadenopathy (10-20%)
* Mono-like presentation (<1% of all mono-like illnesses) * Chorioretinitis * Very rare: myocarditis, myositis Toxoplasma gondii: Immunocompromised hosts * Often life-threatening * Almost always reactivation of latent infection * AIDS o Encephalitis most common manifestation o Usually subacute onset/focal (if CD4< 200) o Mental status changes, seizures, weakness, cranial nerve abnormalities, cerebellar signs, o Can present as acute hemiparesis/language deficit o Usually multiple ring-enhancing lesions on CT/MRI * Pneumonitis * Chorioretinitis Toxoplasma gondii: Clinical manifestations * Immunocompromised hosts o Non-AIDS (transplants, hematologic malignancies) * Congenital * Acute infection asymptomatic in mother * Clinical manifestations range: no sequelae to sequelae that develop at various times after birth o Chorioretinitis o Strabismus o Blindness o Epilepsy, mental retardation, pneumonitis, microcephaly, hydrocephalus, spontaneous abortion, stillbirth Toxoplasma gondii: diagnosis * Clinical suspicion crucial * Serology is primary method of diagnosis o IgM, IgG * Histopathology o Tachyzoites in tissue sections or body fluid (difficult to stain) o Multiple cysts near necrotic, inflammatory lesions Toxoplasma gondii: Treatment * Immunocompetent adults are usually not treated unless visceral disease is overt or symptoms are severe and persistent * Immunodeficient patients * Congenital: Ascaris lubricoides Ascaris lumbricoides * In GI tract, few symptoms in light infectionst. * Pulmonary: symptoms due to migration Effects of Adult Ascaris Worms * Depends on worm load * Effects * Toxic and Metabolic Ascaris lumbricoides Diagnosis * Characteristic eggs on direct smear examination * If treating mixed infections, treat Ascaris first o Mebendazole 100 mg bid x 3 days o Pyrantel 10 mg/kg single dose * Control: o Periodic mass treatment of children, health education, environmental sanitation Enterobius (Pinworm) * 18 million infections in U.S. * Incidence higher in whites * Preschool and elementary school most often * Mostly asymptomatic * Nocturnal anal pruritis cardinal feature due to migration and eggs * May have insomnia, possible emotional symptoms * DS-eggs or adults on perineum {scotch tape} * Mebendazole 100 mg. Repeat in 2 weeks. Pyrantel pamoate 11 mg/kg; repeat 2 weeks Strongyloides Strongyloides: Crucial Aspects of Life Cycle * Infection acquired through penetration of intact skin * Infection may persist for many years via autoinfection * In immunocompromised patients, there is risk of dissemination or hyperinfection o Hyperinfection syndrome Disseminated Strongyloidiasis * High mortality 75% * Penetration of gut wall by infective larvae * Gut organisms carried on the surface of larvae results in polymicrobial sepsis, meningitis * Larvae disseminate into all parts of body: CNS, lungs, bladder, peritoneum Summary—Clinical Findings * Defective cell-meditated immunity: steroids, burns, lymphomas, AIDS (?) * Gl symptoms in about two-thirds: o Abdominal pain o Bloating o Diarrhea o Constipation * Wheezing, SOB, hemoptysis Summary—Clinical Findings * Skin rash or pruritis in ~ one-third * Eosinophilia 60-95% * Less if on steroids Hookworm * Hookworm responsible for development of USPHS * Caused by two different species (North American and Old World) * Very similar to strongyloides in life cycle * Attaches to duodenum, feeds on blood * Elaborates anticoagulant, attaches and reattaches many times * Loss of around 0.1 ml/d of blood per worm Cutaneous larva migrans (creeping eruption) * Caused by filariform larvae of dog or cat hookworm (Ancylostoma braziliense or Ancylostoma duodenale * Common in Southeast U.S. * Red papule at entry with serpiginous tunnel * Intense pruritis * Self limiting condition * Diagnosis clinical * Topical or oral thiabendazole 25 mg/kg bid for 3-5 days * May use ethyl chloride topically * More common in children o Larvae penetrate skin and cause tingling followed by intense itching. * Eggs shed from dog and cat bowels develop into infectious larvae outside the body in places protected from desiccation and extremes of temperature * Shady, sandy areas under houses, at beach, etc. Usually not associated with systemic symptoms * Diagnosis and treatment * Skin lesions are readily recognized * Usually diagnosed clinically * Generally do not require biopsy # Reveal eosinophilia inflammatory infiltrate # Migrating parasite is generally not seen * Stool smear will reveal eggs Visceral Larva Migrans * Infection with dog or cat round worms * Toxocara canis; Toxocara catis * Underdiagnosed based on seroprevalence surveys * Heavy infections associated with fever, cough, nausea, vomiting, hepatomegaly, and eosinophilia * Uncommon in adults * Ocular type more common in adults * Diagnosis-ELISA * Thiabendazole: 25 mg/kg bid X 5 days Echinococcosis Hydatid Disease Echinococcosis * Clinical manifestations: o Most patients are asymptomatic + Dx’d incidentally on an imaging study o Sxs generally develop when the hydatid cyst reaches 8-10 cm (often over decades) + Compress vital structures + Erode into biliary tract or bronchus o Cysts can become superinfected o Leakage or rupture can result in anaphylactic reaction  fever, hypotension Echinococcosis * Diagnosis: o US, CT or MRI + Characteristic hydatid cyst with septated daughter cysts + May see head of the tapeworm o ELISA + Highly sensitive for liver cysts, less so for other organs Echinococcosis (Treatment) * Surgical resection of cyst * To reduce risk of spread: o Aspirate cyst o Instill hypertonic saline, iodophor, 95% ethanol to kill germinal layer and daughter cysts o No cidal agents in cases with biliary communication  risk of sclerosing cholangitis * Percutaneous aspiration-injection-reaspiration (PAIR) * Albendazole before and after surgery or PAIR Schistosomiasis Schistosomiasis: Epidemiology and life cycle Schistosomiasis: Clinical manifestations Schistosomiasis: Diagnosis and treatment * Detection of characteristic eggs in stool, urine or tissue biopsy is diagnostic o Urine is best between 12N and 2Pm, passed through 10 µm filter to concentrate eggs * Antibody tests are available, but limited by sensitivity, specificity * Praziquantel is the drug of choice S. mansoni Stool S. haematobium Urine S. japonicum African trypanosomiasis Trypanosoma brucei gambiense Blood smear Tsetse fly Treatment * Suramin * Melasoprol American trypanosomiasis Blood smear Reduviid bug (assassin bug) Chagas disease: Clinical manifestations Chagas disease: Diagnosis and treatment * Acute disease is diagnosed by seeing trypomastigotes on peripheral blood smear * Chronic disease is diagnosed by ELISA detecting IgG antibody to T. cruzi * Both acute and chronic disease can be treated with nifurtimox or benznidazole * Treatment slows the progression of heart disease Chagas Disease * Public health implications in the US * Chronic o Cardiomyopathy o Megaesophagus o Magacolon * Blood transfusion * Transplant o Solid organ o Musculoskeletal allograft tissue Tapeworms (Cestodes) * Adult worms inhabit GI tract of definitive vertebrate host * Larvae inhabit tissues of intermediate host * Humans o Definitive for T. saginata o Intermediate for Echinococcus granulosus (hydatid) o Both definitive and intermediate for T. solium * Adult worms shed egg-containing segments in stool ingested by intermediate host larval form in tissues Taenia saginata * Ingestion of raw or poorly cooked beef * Cows infected via the ingestion of human waste containing the eggs of the parasite * Cows contain viable cysticercus larvae in the muscle * Humans act as the host only to the adult tapeworms * Up to 25 meters in the lumen of intestine * Found all over the world, including the U.S. Beef Tapeworm Treatment * Praziquantel * Albendazole * Niclosamide Cystercercosis * Human infected with the larval stage of Taenia solium * Humans can serve as definitive or intermediate host * Eggs are ingested, or possibly get to stomach by reverse peristalsis * Probably much more common than is reported, since most infections are asymptomatic Cystercercosis * Symptoms depend on location of cysts, but frequently include motor spasms, seizures, confusion, irritability, and personality change * In the eye, often subretinal or in vitreous. Movement may be seen by the patient. Pain, amaurosis, and loss of vision may occur. * Clinical manifestations Cysticercosis * Diagnosis o CT and MRI preferred studies + Discrete cysts that may enhance + Usually multiple lesions # Single lesions especially common in cases from India + Older lesions may calcify o CSF + Lymphs or eos, low glucose, elevated protein o Serology + Especially in cases with multiple cysts Cysticercosis * Treatment o Complex and controversial o Praziquantel and albendazole may kill cysts, but death of larvae can increase inflammation, edema and exacerbate sxs o When possible, surgical resection of symptomatic cyst is preferred o Corticosteroids vs. edema and inflammation; antiseizure meds Babesiosis * Babesiosis caused by hemoprotozoan parasites of the genus Babesia * >100 species reported
* Few actually cause human infection
* Babesia microti
* Life cycle involves two hosts:
o Deer tick, Ixodes dammini, (definitive host) introduces sporozoites into white-footed mouse
* Once ingested by an appropriate tick gametes unite and undergo a sporogonic cycle resulting in sporozoites
* Humans enter cycle when bitten by infected ticks
Deer are the hosts upon which the adult ticks feed and are indirectly part of the Babesia cycle as they influence the tick population
* Clindamycin* plus quinine
* Atovaquone* plus azithromycin*
* Exchange transfusion in severely ill patients with high parasitemia

Classification of Parasitic Diseases
* Protozoa: amoeba; flagellates; ciliates; apicomplexa; microspors (primitive intracellular parasites)
* Metazoa (two phyla)
o Helminths (worms)
+ Nematodes
# Intestinal
# Extra-intestinal
+ Flatworms (platyhelminths)
# Cestodes (tapeworms)
# Trematodes (flukes)
o Arthopods (ectoparasites): scabies, lice, fly larvae

General rules of treatment
* Protozoa: require species-specific treatment
* Metozoa: species-specific

General rules of treatment of metazoa
Nematodes
Intestinal
Mebendazole or Albendazole
Tissue
Albendazole
Filiariae
Ivermectin, doxycycline
Cestodes
Praziquantel, Albendazole, Niclosamide
Trematode
Praziquantel
Ectoparasites
Permethrin, Ivermectin
This is just the beginning of a great adventure in infectious diseases
Sine qua non:history and physical examination

Emerging Infections and Medical Procedures.ppt

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Chronic Pelvic Pain

Chronic Pelvic Pain
By:Jennifer Griffin, MD
M3 Student Clerkship Lecture
University of Nebraska Medical Center

Chronic Pelvic Pain
* Definition = Pain of apparent pelvic origin that has been present most of the time for 6 months
* Difficult to diagnose.
* Difficult to treat.
* Difficult to cure.
* =Physician and patient frustration.

Just because you’re a hammer doesn’t necessarily make every problem a nail.

Chronic Pelvic Pain
* Gynecologic
* Gastrointestinal
* Urologic
* Musculoskeletal/ Pelvic Floor
* Psychological
* United Kingdom data:
o Urinary dx 30.8%
o GI dx 37.7%
o Gynecologic 20.2%
o 25-50% have >1 dx
o MC Dx = endometriosis, adhesions, IBS, IC
Getting the History
* Nature of the Pain:
o Sharp, stabbing, colicky, burning?
o Where specifically is it located?
* Timing of the Pain:
o Does it come and go or is it constant?
o Does it occur with certain activities?
o Is it related to menses?
o Is it consistent and predictable?
* Modifying factors:
o Can you do anything to make it better/ worse?

Review of Systems
* Gynecologic:
o Association with menses?
o Association with sexual activity? (be specific)
o New sexual partners/ practices?
o Symptoms of vaginal dryness / atrophy?
o Other changes in menses?
o Use of contraceptives?
o Childbirth history and any associations?
o History of pelvic infections?
o History of other gyn problems/ surgeries?
* Gastrointestinal:
o Regularity of bowel movements?
o Diarrhea/ constipation/ flatus?
o Relief with defecation?
o History of hemorrhoids/ fissures/ polyps?
o Blood in stools, melena, or mucous?
o Nausea, vomiting, or appetite change?
o Weight loss?
* Urologic:
o Pain with urination?
o History of frequent / recurrent UTIs?
o Blood in urine?
o Symptoms of urgency or incontinence?
o Difficulty voiding?
* Musculoskeletal:
o History of trauma?
o Association with back pain?
o Other chronic pain problems?
o Association with position or activity?
* Psychological:
o History of abuse (verbal/ physical/ sexual)?
o Diagnosis of psychiatric disease?
o Association with life stressors?
o Exacerbated by life stressors?
o Family/ spousal support?
Chronic Pelvic Pain
* Diagnosis
o History and Physical
o Targeted imaging studies (U/S best for gyn evaluation)
o EMB/D&C
o Laparoscopy
o Cystoscopy/ Colonoscopy
o Physical therapy evaluation
* Gynecologic Origin
o Endometriosis
o Primary Dysmenorrhea
o Leiomyomas
o Dyspareunia
o Vaginismus
o Adenomyosis
o Infectious causes
o Pelvic congestion syndrome
o Pelvic organ immobility
o Cancer
* ACOG Practice

Gyn Causes
* Cyclic:
o Primary dysmenorrhea
o Endometriosis
o Adenomyosis
o Mittleschmertz
* Non-cyclic:
o Pelvic masses
o Adhesions
o Infections
o Non-gyn causes
* Related to intercourse:
o Endometriosis
o Vaginismus
o Vaginal atrophy
o Musculoskeletal
o Any non-cyclic cause could be exacerbated.

Chronic Pelvic Pain: Cyclic
* Endometriosis
Chronic Pelvic Pain: Cyclic
* Endometriosis: Etiology
* Endometriosis: Classic Triad
* But may present with:
o Chronic pelvic pain
o Adnexal mass
* Endometriosis: Diagnosis
* Endometriosis:
* Endometriosis: Treatment
* Dysmenorrhea
* Leiomyomas
* Adenomyosis
* Dyspareunia
* Vaginismus

Chronic Pelvic Pain: Dyspareunia
* Pelvic Floor Muscle Spasm and Strain
Chronic Pelvic Pain: Non-cyclic
* Pelvic congestion syndrome
* Pelvic organ immobility
* PID
* Infectious causes
* Gynecologic malignancies
* Other Gynecologic origin:
* Treatment of Gynecologic Problems
* Urologic Origin, Level A:
o Bladder malignancy
o Interstitial Cystitis
o Radiation Cystitis
o Urethral Syndrome
* Bladder origin, Level B:
* Urologic origin, Level C:
* Urologic origin
* Urologic origin: Interstitial Cystitis
* Gastrointestinal Origin, Level A:
* IBS
* Irritable Bowel Syndrome
* IBS Treatment
* Colon carcinoma
* Constipation
* Inflammatory Bowel Disease
* Gastrointestinal origin, Level C (no Level B):
* Musculoskeletal, Level A:
* Musculoskeletal origin, Level B:
* Musculoskeletal origin, Level C:
* Other Non-Gynecologic Origin, Level A:
* Psychological
* Other Non-Gynecologic origins, level B:
* Other Non-Gynecologic origin, Level C:
Clinical Pearl of Wisdom
Pelvic Pain Treatment Triad
* Medical treatment of most likely diagnosis.
* Psychiatric evaluation and treatment.
* Pelvic physical therapy.

Case Studies
Chronic Pelvic Pain
* Conclusions:
o Thorough history and physical
o Imaging and lab studies
o Many treatment options available

Chronic Pelvic Pain.ppt

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Pelvic Pain – Dysmenorrhea and Endometriosis

Pelvic Pain – Dysmenorrhea and Endometriosis

* A 20 y.o. woman presents to her gynecologist with a 4 year history of increasing lower abdominal pain with her menses. The pain begins on the first day of her menses and lasts 2-3 days. She also complains of lower back pain and nausea. Menarche occurred at the age of 13 and her menses occur every 28 days and last 5 days. Physical and pelvic exam are normal.

* How is dysmenorrhea diagnosed? How is it distinguished from other types of pelvic pain?
* What is the pathophysiology of dysmenorrhea?
* What are reasonable approaches to treatment?

Dysmenorrhea
* Dysmenorrhea – severe, painful cramping sensation in the lower abdomen often accompanied by other symptoms – sweating, tachycardia, headaches, n/v, diarrhea, tremulousness, all occurring just before or during menses
- Primary: no obvious pathologic condition, onset < 20 years old - Secondary: associated with pelvic conditions or pathology Primary Dysmenorrhea * Pathogenesis: elevated PG F2α in secretory endometrium (increased uterine contractility) * Treatment: NSAIDs – PG synthetase inhibitors – 1st line treatment of choice * Other treatment options: OCPs, other analgesics Secondary Dysmenorrhea * Etiologies - Cervical Stenosis - Endometriosis and Adenomyosis - Pelvic Infection - Adhesions - Pelvic Congestion - Stress and Tension * Cervical Stenosis - Severe narrowing of cervical canal may impede menstrual outflow – congenital or iatrogenic - can cause an increase in intrauterine pressure during menses - can lead to endometriosis * Cervical Stenosis - Hx – scant menstrual flow, severe cramping throughout menses - Dx – inability to pass a thin probe through the internal os OR HSG demonstrates thin cx canal - Tx – cervical dilation via D&C or laminaria placement * Pelvic Congestion - Due to engorgement of pelvic vasculature - Hx – burning or throbbing pain, worse at night and after standing - Dx – Laparoscopic visualization of engorgement/varicosities of broad ligament and pelvic sidewall veins Evaluation of Pelvic Pain * Detailed history, targeted physical exam, labs (UA, UCx, CBC, HCG, tumor markers), diagnostic imaging studies (US, MRI, CT) as appropriate * Consider age of patient * “OLDCAAR”: onset, location, duration, context, associated sx, aggravating/relieving factors * Temporal characteristics: cyclic (e.g. dysmenorrhea), intermittent (e.g. dyspareunia), non-cyclic * Risk factors * GYN and Non-GYN causes DDx Pelvic Pain - GYN * GYN - Uterus - fibroids, adenomyosis, endometritis - Fallopian tubes - PID/salpingitis, hydrosalpinx, ectopic - Ovaries - cysts – functional, pathological, TOA, torsion; mittleschmerz - Other - endometriosis, adhesions, IUD/infection, severe prolapse DDx Pelvic Pain – Non-GYN * Urologic - UTI/urethritis, interstitial cystitis (IC), OAB, urethral diverticulum, nephrolithiasis, malignancy * GI - constipation, IBS, IBD (Crohn’s, UC), bowel obstruction, diverticulitis, malignancy, appendicitis * Musculoskeletal - trigger points, fibromyalgia, hernias, neuralgia, low back pain * Other - psychiatric – depression, somatization; abdominal cutaneous nerve entrapment in surgical scar; celiac disease Case 1 * At the age of 30, the patient presents with a 2 year history of infertility. Her menses are still regular but she has 2-3 days of spotting before her menses are due. She also complains of pain with intercourse and pelvic pain. In reviewing the patient’s history, the gynecologist notes that over the past year the patient was repeatedly treated by her internist with antibiotics for recurrent microscopic hematuria. * What is the most likely diagnosis? * What are the main theories regarding the pathogenesis in this case? * How would you evaluate and treat this patient? Endometriosis - Symptoms * Variable and unpredictable - asymptomatic - dysmenorrhea - CPP - deep dyspareunia - sacral backache w/ menses - dysuria +/- hematuria (bladder involvement) - dyschezia/hematochezia (bowel involvement) Endometriosis – Physical Exam * Uterosacral nodularity * Adnexal mass (endometrioma) * Normal exam Endometriosis - Incidence * 7-10% of general population * 20-50% of infertile women * 70-85% in women w/ CPP * No racial predisposition * +Familial association with almost 10x increased risk of endometriosis if affected 1st degree relative Endometriosis - Pathogenesis * Retrograde menstruation (Sampson) * Hematogenous or lymphatic spread (Halban) * Coelomic metaplasia (Meyer/Novack) * Iatrogenic dissemination * Immunologic defects (Dmowski) * Genetic predisposition Endometriosis - Pathogenesis * Retrograde menstruation (Sampson’s theory) - Monkey experiments – sutured cervix closed to create outflow obstruction caused development of endometriosis - Clinical observation of retrograde menstrual flow during laparoscopy in humans - Increased risk of endometriosis in women with cervical/vaginal atresia, other outflow obstruction - Increased risk with early menarche, longer and heavier flow - Decreased risk with decreased estrogen levels e.g. exercise-induced menstrual disorders, decreased body fat, + tobacco use Endometriosis - Pathogenesis * Hematogenous or lymphatic spread - Endometriosis found in remote sites – lung, nose, spinal cord, pelvic lymph nodes. Endometriosis - Pathogenesis * Coelomic metaplasia - Mullerian ducts are derived from coelomic epithelium during fetal development - Hypothesize that coelomic epithelium retains ability for multipotential development - Endometriosis seen in prepubertal girls, women w/ congenital absence of the uterus, and RARELY in men Endometriosis - Pathogenesis * Iatrogenic dissemination - Endometriosis has been found in cesarean section scar * Immunologic defects * Genetic predisposition - polygenic, multi-factorial Endometriosis - Diagnosis * Laparoscopy with biopsy proven histologic diagnosis – standard for dx of endometriosis * Empiric medical treatment with improvement in symptoms * CA 125 – NOT considered to be of clinical utility * Imaging – US, MRI, CT – only useful in the presence of pelvic or adnexal masses (endometriomas) * Laparoscopy with biopsy proven histologic diagnosis – standard for dx of endometriosis - Extent of visible lesions do not correlate with severity of sx, but depth of infiltration of lesions seems to correlate best with pain severity - classic powder-burn lesions, endometriomas - lesions can be red, clear or white – more commonly seen in adolescents * Endometrial epithelium * Endometrial glands * Endometrial stroma * Hemosiderin-laden macrophages 2 or more of the following histologic features are criteria for Dx: * Imaging – US, MRI, CT – only useful in the presence of pelvic or adnexal masses (endometriomas) - on US, endometriomas appear as cysts that contain low-level homogeneous internal echoes consistent with old blood (ddx includes hemorrhagic cysts) Endometriosis - Treatment * Medications - Progestins - OCPs – continuous vs. cyclic – if no relief in 3 months, consider tx with Depo Provera or GnRH agonist - NSAIDs - GnRH agonists – most expensive - Danazol – appears to be as effective as GnRH agonist for pain relief but with increased side-effects * GnRH agonists – create a state of relative estrogen deficiency – vasomotor side effects and potential decrease in bone density - 12-month course of GnRH agonist therapy associated with 6% decrease in bone density - No data regarding extended treatment with GnRH agonists beyond 1 year * Add-back therapy is advocated for women undergoing long-term therapy (i.e. > 6 months)
* Some evidence to suggest that immediate add-back therapy may result in even less bone loss
- Add-back regimens: progestins alone, progestins + bisphosphonates, low-dose progestins + estrogens, pulsatile PTH

Endometriosis – Treatment Considerations in Adolescents
* GnRH treatment is NOT recommended for patients < 18 years because the effects of these medications on bone formation and long-term bone density have not been adequately studied * Depo provera used for longer than 2 years has been shown to decrease bone density in adolescents – FDA warning against long-term use * If no improvement in symptoms after 3 months of empiric treatment with NSAIDs and OCPs, diagnostic laparoscopy should be offered Endometriosis - Treatment * Surgery - Laparoscopic laser vaporization vs. cauterization vs. excision - Ovarian cystectomy for endometrioma - Hysterectomy +/- BSO * Medications vs. Surgery - Lack of data to support surgery vs. medical treatment for tx of pain symptoms due to endometriosis - Starting with empiric medical therapy is appropriate - Offer GnRH agonist therapy if initial medical treatment with OCPs and NSAIDs not helping - Cost of comparing empiric medical management with definitive surgical diagnosis is difficult to assess, but 3 months of empiric treatment is less than a laparoscopic procedure .... Pelvic Pain – Dysmenorrhea and Endometriosis.ppt

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Urinary Tract Infections

Urinary Tract Infections
By:Lourdes Lozano Vargas

Urinary Tract Infections
* Leading cause of morbidity and health care expenditures in persons of all ages.
* An estimated 50 % of women report having had a UTI at some point in their lives.
* 8.3 million office visits and more than 1 million hospitalizations, for an overall annual cost > $1 billion.

Acute Uncomplicated Cystitis
* Sexually active young women.
* Causes: anatomy and certain behavioral factors, including delays in micturition, sexual activity, and the use of diaphragms and spermicides tract.
* Aggressive diagnostic work-ups are unwarranted in young women presenting with an uncomplicated episode of cystitis.

Acute Uncomplicated Cystitis
* The microbiology is limited to a few pathogens.
* 70%- 85% are caused by Escherichia coli
* 5-20%are caused by coagulase-negative Staphylococcus saprophyticus
* 5-12% are caused by other Enterobacteriaceae such as Klebsiella and Proteus.

Acute Uncomplicated Cystitis
* Clinical Features: dysuria, frequency, urgency, suprapubic pain, hematuria.
o Fever >38C, flank pain, costovertebral angle tenderness, and nausea or vomiting suggest upper tract infection.

Acute Uncomplicated Cystitis
* Diagnosis: direct history and PE
* PE: Temperature, abdominal exam, assessment of CVA tenderness, pelvic exam.
o H/o STD’s, new sexual partner, partner with urethral symptoms, gradual onset.

Acute Uncomplicated Cystitis
* Guidelines for tx of acute cystitis recommend empiric antibiotic tx.
* Unnecessary antibiotic use??
* Clinical criteria for Dx:

Dysuria, presence of > trace urine leukocytes, and presence of nitrites or...
Dysuria and frequency in the absence of vaginal discharge.
Acute Uncomplicated Cystitis
* UA: Evaluation of midstream urine for pyuria.
o White blood cell casts in the urine are Dx of upper tract infection.
* Urine Culture: Not necessary
o Warranted in: Suspected complicated infection, persistent symptoms following tx, symptoms recur < 1 mo after tx. Acute Uncomplicated Cystitis * Urine dipsticks: o Leukocyte esterase (pyuria), sensitivity 75-90%, specificity 95% o Nitrite (Enterobacteriacea), sensitivity 35-85%, specificity 95%, false positive with phenazopyridine, beets. o Microscopic evaluation for pyuria or a culture is indicated in pt with negative leukocyte esterase that have urinary symptoms. Acute Uncomplicated Cystitis * Susceptibility: o E.coli o S.saprophyticus Acute Uncomplicated Cystitis * Treatment: o Short course vs. prolonged tx + Short course preferred except with beta-lactam agents o TMP-SMX (160/800mg BID x 3) first-line tx if: no allergy to the drug, no antibiotics in the past 3 mo, no recent hospitalization. o Nitrofurantoin (100mg BID x 5 days) o Analgesia: Phenazopyridine 200mg TIDx2 Acute Urethral Syndrome * Acute symptomatic women with dysuria and frequency with a midstream culture containing < 10(5) CFU/mL. * > 10(2) CFU/mL in women with acute symptomatic pyuria = UTI
* Tx as an uncomplicated UTI
* Mycoplasma genitalium, Ureaplasma urealyticum

Acute Complicated Cystitis
* UTI when/with structural, functional or metabolic abnormalities (polycystic, solitary, transplant kidney;DM, CRF, indwelling cath, neurogenic bladder) or elderly, male, child, pregnant or h/o recurrent UTI)
* E.coli accounts for fewer than one third of complicated cases.
* Clinically, the spectrum of complicated UTIs may range from cystitis to urosepsis with septic shock.

Acute Complicated Cystitis
* Urine culture and susceptibility are necessary.
* These infections are usually associated with high-count bacteriuria (> 10(5) CFU/mL).
* MO: Proteus, Klebsiella, Pseudomonas, Serratia, and Providencia, enterococci, staphylococci and fungi AND E.coli

Acute Complicated Cystitis
* Empiric therapy for these patients should include an agent with a broad spectrum of activity against the expected uropathogens: fluoroquinolone, ceftazidime, cefepime, aztreonam, imipenem-cilastatin. (Obtain Ucx prior to Tx)
* Tx x 7-14 days
* Follow-up urine culture should be performed within 14 days after treatment???

Recurrent Cystitis
* Up to 27% of young women with acute cystitis develop recurrent UTIs.
* The causative organism should be identified by urine culture.
* Relapse: infection with the same organism (multiple relapses = complicated UTIs).
* Recurrence: infection with different organisms.

Recurrent Cystitis
* >3 UTI recurrences documented by urine Cx within one year can be managed using one of three preventive strategies:
* Acute self-treatment with a three-day course of standard therapy.
* Postcoital prophylaxis with one-half of a TMP-SMX double-strength tablet (80/400 mg).
* Continuous daily prophylaxis TMP-SMX one-half tablet per day (40/200 mg); nitrofurantoin 50 to 100 mg per day; norfloxacin 200 mg per day.

Uncomplicated Pyelonephritis
* Suspect if:
o Cystitis-like illness and accompanying flank pain
o Severe illness with fever, chills, nausea, vomiting, abdominal pain
o Gram-negative bacteremia.

Uncomplicated Pyelonephritis
* DX: Clinical, confirm with:
o UA: pyuria and/or WBC casts
o UCx with > 10 (5) CFU/mL (80%)
* Tx: 14 days total
o Oral: TMP/SMX, fluoroquinolones
o IV: 3rd gen cephalosporin, aztreonam, quinolones, aminoglycoside

Uncomplicated Pyelonephritis
* Pt with symptoms after 3 days of appropriate antimicrobial tx should be evaluated by renal US or CT for obstruction or abscess.

UTI in Men

* At risk: Older men with prostatic disease, UT instrumentation, anal sex, or partner colonized with uropathogens.
* UCx: 10 (3) CFU/mL sensitivity and specificity 97%.
* Additional studies?
o Not necessary in young healthy men who have a single episode.

UTI in Men
* Tx:
o Uncomplicated cystitis:
+ TMP/SMX or fluoroquinolones x 7 days
o Complicated cystitis:
+ Fluoroquinolones x 7-14 days
o Bacterial prostatitis:
+ Fluoroquinolone x 6-12 weeks

Catheter-Associated UTI
* Risk of bacteriuria is ~ 5%/day (long term catheter bacteriuria is inevitable).
* 40% of nosocomial infections
* Most common source of gram-negative bacteremia.
* Dx: Ucx 10 (2) CFU/mL
o MO: E.coli, Proteus, Enterococcus, Pseudomona, Enterobacter, Serratia, Candida

Catheter-Associated UTI
* Mild to mod: oral quinolones10-14days
* Severe infection: IV/oral 14-21days
* Asymptomatic bacteriuria in pt with an indwelling Foley should not be Tx unless they are immunosuppressed, have risk of bacterial endocarditis or pt who are about to undergo urinary tract instrumentation.

Asymptomatic Bacteriuria
* UCx: > 10(5)CFU/mL with no symptoms
* Three groups of pt with asymptomatic bacteruria have been shown to benefit from tx:
o Pregnant
o Renal transplant
o Pt who are about to undergo urinary tract procedures.

Pregnant patients

* Asymptomatic bacteriuria: two consecutive voided urine specimens with isolation of the same bacterial strain >10(5) or a single cath urine specimen.
o Nitrofurantoin 100mg BID x 5-7 days
o Amoxi/Clav 500mg BID or 250 TID x 7days
o Fosfomycin 3g PO x 1

Interstitial Cystitis
* Frequency, urgency, urge incontinence with periurethral and suprapubic pain on bladder filling that is improved by voiding. Terminal hematuria may be present.
* Etiology. Unclear (autoimmune, altered glycosaminoglycal layer, allergic)

Interstitial Cystitis
* TX
o Refer to urology for cystoscopy.
o Dietary modifications
o Behavioral modifications
o Rx:
+ Pyridium
+ Pentosan polysulfate 100mg TID x 6mo to 2 years.
+ Amitriptyline 10-75mg QHS

Interstitial Cystitis
* Intravesical therapies
o Dimethyl Sulfoxide instillations q1-2 wks
o BCG instilled q1wk x 6-8 wks
o Hyaluronic acid instilled q1wk x 4-6wk.

References

Urinary Tract Infections.ppt

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Oral Cavity

Oral Cavity
By:Robert Scranton© 2008

The Tissues
Lining Mucosa
Masticatory Mucosa
* NKSS (nonkeratinized stratified squamous)
* Lamina Propria- loose CT w/ collagen bundles
o Mucous and serous glands
o Fordyce Spots
* Location?
* KSS/PKSS (keratinized/parakeratinized stratified squamous)
* Variable Lamina Propria
* Location?

Lining Mucosa
Don’t forget the soft palate
Diagrams are important

Identify:
* vermillion zone
* Hair follicle
* Epithelium, what type?
* Skeletal muscle
o what is the name?

Special Mucosa
* Filiform
o Most abundant
o Dorsal surface
* Fungiform
o Occasional tasebuds, CN-VII
* Vallate
o 8-12 along sulcus terminalis
o Crypt
o Serous glands of Von Ebner
o CN- IX, taste buds
* Foliate
o Dorsolateral surfaces, taste buds?

Identify filiform and fungiform
Vallate/ circumvallate

Teeth
* We origionally have __ baby (________) teeth. Adults have ___ teeth.
* What are the three cell types that form the teeth and what parts do they form?
* What do dentin and enamel have in common?
* Which is acellular?

Mesenchymal CT pulp cavity
Odontoblasts (mesenchyme) Dentin
ameloblasts (ectoderm) Enamel
Avascular
Ca2+ Hydroxyapatite (calcified organic Matrix
Enamel
Teeth
* The little tubules in the teeth, what is their story?
* Damage to What three things can lead to loss of a tooth?
* Dentinal tubules- the tubule that the cytoplasmic process of odontoblasts extend through for nociception
* Canaliculi- the tubules that cementocytes use to maintain cementum
* Bony Socket
* Peridontal ligament
* Cementum

Identify:
* Alveolar Bone
* Free Gingiva
* Attached Gingiva
* Alveolar Mucosa
* Gingival Ligament
* Gingival Sulcus
* Alveolar Bone
* Dentin
* Peridontal ligament
* Pulp Cavity
* Gingiva
* Odontoblasts
* Predentin
* Dentin
* Cementocytes
* Peridontal Ligament

Salivary Glands
Intrinsic
Extrinsic
* AKA minor
* Serous
* Mucous
* Mixed
* Means w/in lamina propria
* AKA Major
* Serous
* Serousmucous
* Outside oral cavity
* Has large ducts

Important words
* Serous amylase
* Serous demilunes bacteriolytic lysozyme
* IgA bacteriostatic, resistant to degradation
* Nasopharynx Respiratory Epithelium
* Oropharynx lining mucosa, NKSS
* Laryngopharynx transitional zone so KSS, NKSS

Oral Cavity.ppt

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Chemical composition and functions of saliva

Chemical composition and functions of saliva
By:Dennis E. Lopatin, Ph.D.

Chronology of defining salivary components and functions
* Beginning in 1950’s whole saliva evaluated (antimicrobial properties, role in microbial attachment, mineralization, taste, lubrication)
* Secretions of major glands (parotid and submandibular/sublingual)
* In 1970’s individual components isolated and biochemically characterized
* In mid-1980’s beginning to map functional domains (peptide synthesis and recombinant approaches)

Major salivary components
Mucin 1 (MG1)
sIgA
Mucin 2 (MG2)
Lactoferrin
Peroxidases
Amylases
Carbonic anhydrases
Proline-rich proteins
Lysozyme
Statherins
Histatins

Current concepts regarding the functional features of salivary macromolecules
* Recent structure/function studies have identified general principles regarding function
* Based on in vitro studies of purified molecules
* Additional studies required to evaluate concepts in situ

Conformational requirements
* Conformation or shape of a molecule is critical for its biological function
* Examples
o Proline-rich proteins interact with A. viscosus and St. gordonii only when adsorbed onto mineralized surface
o Statherins and histatins require -helical conformation
o Human salivary amylase require 5 inter-chain disulfide bonds

Multifunctionality
Salivary
Families
Anti-Bacterial
Buffering
Digestion
Mineralization
Lubrication &Viscoelasticity
Tissue
Coating
Anti-Fungal
Anti-Viral
Carbonic anhydrases,
Histatins
Amylases,
Mucins, Lipase
Cystatins,
Histatins, Proline rich proteins,
Statherins
Mucins, Statherins
Amylases,
Cystatins, Mucins,
Proline-rich proteins, Statherins
Histatins
Cystatins,
Mucins
Amylases, Cystatins,
Histatins, Mucins,
Peroxidases
Redundancy
* Saliva has built-in redundancy in regard to its protective functions.
* Example - Many salivary molecules can inhibit the precipitation of calcium phosphate salts.
o strong inhibitors such as statherin and acidic proline-rich proteins
o moderate inhibitors such as histatins and cystatins
o weak inhibitors such as mucins and amylase

Amphifunctionality
* A molecule may have both protective and detrimental properties - “double-edged sword”.
* May depend on molecule’s location or site of action
o Amylases
+ In solution, they facilitate clearance of viridans streptococci
+ Adsorbed to tooth surface, they can promote adherence of these bacteria and digest starch to dietary maltose and production of acid
o Statherin and acidic proline-rich proteins
+ At enamel surface, they play an important role in mineralization by inhibiting the formation of primary and secondary calcium phosphate salts. When adsorbed to the enamel surface, they promote attachment of cariogenic microorganisms.

Complexing
* Functional relationships exist between different molecules in saliva
* Two types of complexing (covalent and non-covalent)
o homotypic (between similar molecules)
o heterotypic (between different molecules)
* Example: Mucins
o homotypic complexes necessary for lubrication and viscoelastic properties
o heterotypic complexes with sIgA, lysozyme and cystatins concentrate these anti-microbials at tissue interfaces
Salivary Protein Functions
Mucins
* Lack precise folded structure of globular proteins
* Asymmetrical molecules with open, randomly organized structure
* Polypeptide backbone (apomucin) with CHO side-chains
* Side-chains may end in negatively charged groups, such as sialic acid and bound sulfate
* Hydrophillic, entraining water (resists dehydration)
* Unique rheological properties (e.g., high elasticity, adhesiveness, and low solubility)
* Two major mucins (MG1 and MG2)

Mucin Functions
* Tissue Coating
o Protective coating about hard and soft tissues
o Primary role in formation of acquired pellicle
o Concentrates anti-microbial molecules at mucosal interface
* Lubrication
o Align themselves with direction of flow (characteristic of asymmetric molecules)
o Increases lubricating qualities (film strength)
o Film strength determines how effectively opposed moving surfaces are kept apart
* Aggregation of bacterial cells
o Bacterial adhere to mucins may result in surface attachment, or
o Mucin-coated bacteria may be unable to attach to surface
* Bacterial adhesion
o Mucin oligosaccharides mimic those on mucosal cell surface
o React with bacterial adhesins, thereby blocking them

Amylases
* Calcium metalloenzyme
* Hydrolyzes (1-4) bonds of starches such as amylose and amylopectin
* Several salivary isoenzymes
* Maltose is the major end-product (20% is glucose)
* “Appears” to have digestive function
* Why is it also present in tears, serum, bronchial, and male and female urogenital secretions?
* A role in modulating bacterial adherence?

Lingual Lipase
* Secreted by von Ebner’s glands of tongue
* Involved in first phase of fat digestion
* Hydrolyzes medium- to long-chain triglycerides
* Important in digestion of milk fat in new-born
* Unlike other mammalian lipases, it is highly hydrophobic and readily enters fat globules

Statherins
* Calcium phosphate salts of dental enamel are soluble under typical conditions of pH and ionic strength
* Supersaturation of calcium phosphates maintain enamel integrity
* Statherins prevent precipitation or crystallization of supersaturated calcium phosphate in ductal saliva and oral fluid
* Produced by acinar cells in salivary glands
* Also an effective lubricant

Proline-rich Proteins (PRPs)
* Like statherin, PRPs are also highly asymmetrical
* Inhibitors of calcium phosphate crystal growth
* Inhibition due to first 30 residues of negatively-charged amino-terminal end
* Present in the initially formed enamel pellicle and in “mature” pellicles

Role of PRPs in enamel pellicle formation
* Acquired enamel pellicle is 0.1-1.0 µm thick layer of macromolecular material on the dental mineral surface
* Pellicle is formed by selective adsorption of hydroxyapatite-reactive salivary proteins, serum proteins and microbial products such as glucans and glucosyl-transferase
* Pellicle acts as a diffusion barrier, slowing both attacks by bacterial acids and loss of dissolved calcium and phosphate ions

Remineralization of enamel and calcium phosphate inhibitors
* Early caries are repaired despite presence of mineralization inhibitors in saliva
* Sound surface layer of early carious lesion forms impermeable barrier to diffusion of high mol.wt. inhibitors.
* Still permeable to calcium and phosphate ions
* Inhibitors may encourage mineralization by preventing crystal growth on the surface of lesion by keeping pores open

Calculus formation and calcium phosphate inhibitors
* Calculus forms in plaque despite inhibitory action of statherin and PRPs in saliva
* May be due to failure to diffuse into calcifying plaque
* Proteolytic enzymes of oral bacteria or lysed leukocytes may destroy inhibitory proteins
* Plaque bacteria may produce their own inhibitors

Calcium phosphate precipitation inhibitors and plaque
* Statherin and PRPs might be expected to occur in plaque, have not been detected
* Plaque bacteria produce calcium phosphate inhibitors
* Might be necessary to prevent calcification of bacteria -- happens with dead cells
* Immobilized crystal growth inhibitors can function as nucleators of crystal growth
* Immobilization may occur in plaque, encouraging calculus formation

Interaction of oral bacteria with PRPs and other pellicle proteins
* Several salivary proteins appear to be involved in preventing or promoting bacterial adhesion to oral soft and hard tissues
* PRPs are strong promoters of bacterial adhesion
o Amino terminal: control calcium phosphate chemistry
o Carboxy terminal: interaction with oral bacteria
* Interactions are highly specific
o Depends on proline-glutamine carboxy-terminal dipeptide
o PRPs in solution do not inhibit adhesion of bacteria

These anti-microbial proteins will be discussed in a later lecture
* Secretory Immunoglobulins
* Lactoferrin
* Lysozyme
* Sialoperoxidase
* Cystatins
* Histatins

Summary - Clinical Highlights
* Understanding of salivary mechanisms at fundamental level a prerequisite for
o effective treatment of salivary gland dysfunctions
o modulation of bacterial colonization
o development of artificial saliva other “cutting edge” approaches to salivary dysfunctions and diseases

Chemical composition and functions of saliva.ppt

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