31 October 2010

Neuroanatomical Techniques



Neuroanatomical Techniques

Presentation by
Armin Blesch, Ph.D.
Harvey Karten, M.D.

Objectives

Neuroanatomical techniques
History of modern neuroanatomy
Rudolf  Albert von Kölliker  (1817-1905)
nucleus  of Kölliker (Rexed  lamina X), continuity of axon and neuron
Heinrich  Wilhelm Gottfried Waldeyer (1837-1921)
Introduced  the term “neuron”  and “chromosome”

Camilio  Golgi   (1843-1926)
Golgi  method; Golgi cells;  Golgi apparatus; Golgi  tendon organ; Golgi-Mazzoni  corpuscle
Santiago  Ramon y Cajal (1852-1934)
Cajal's gold-sublimate method for astrocytes
horizontal  cell of Cajal (Retzius-Cajal cell in cortex
interstitial  nucleus of Cajal

Golgi Stain

Common immunohistochemical stains
Golgi: selective random neuron and fibers
Hematoxylin/Eosin: cell stain
Nissl (thionin): cell body stain
Kluver Barrera: mixed cell fiber stain
Weil: myelinated fiber stain
Acetycholine-esterase
Anterograde and Retrograde Tracing
Brief History of Tracing
(Grafstein, 1967)
(Kristensson & Olsson, 1971)
Fink-Heimer stain
(Heimer 1999)

Chromatolysis

http://cclcm.ccf.org/vm/VM_cases/neuro_cases_PNS_muscle.htm
Anterograde tracing with radioactive amino acids
Edwards and Hendrickson
in: Neuroanatomical tract tracing
Retrograde labeling of spinal motor neurons with HRP
Van der Want  et al.1997
Types of tracers
Application of tracers
Uptake Mechanisms
Active uptake:
Passive incorporation: lipophilic substances
Intracellular injection
Transport
Detection
Fluorescence
Enzyme reaction: HRP (WGA-HRP, CTB-HRP)
Antibodies e.g. CTB
Streptavidin-HRP conjugate for biotinylated tracers e.g. BDA, biocytin
Lectins and Toxins
WGA-HRP
Cholera Toxin beta subunit (CTB)
Retrograde, anterograde and transganglionic
Detection: antibody, HRP conjugate, conjugated to fluorophor
Application: 1 % aqueous solution, iontophoresis or pressure injection
Different efficiency in labeling among different neuronal populatioins and species
Transganglionic tracing of sensory axons with CTB
PHA-L
Anterograde tracing with PHA-L
Gerfen et al. in:
Neuroanatomical tract tracing
FITC/RITC
Fluoresceine isothiocyanate (FITC): green Rhodamine isothiocyanate (RITC): emission >590 nm (red)
Anterograde and retrograde transport
Pressure injection of 1-3% aqueous solution
Lipophilic Carbocyanine Dyes
Lipophilic Carbocyanine Dyes
Labeling of radial glia
Thanos et al. 2000
Dextran amines
Biotinylated dextran amine (BDA)
BDA
Reiner et al. 2000
Anterograde tracing of corticospinal axons
Biocytin/Neurobiotin
Application: 5% solution, pressure injection or iontophoresis
Fast degradation-short survival time 2-3 days
Mostly anterograde transport
Requires glutaraldehyde fixation
Retrograde tracers
All anterograde tracers are partially transported retrogradely
Purely retrograde tracers:
Fast Blue (FB)
Diamidino Yellow (DiY)
Microspheres
Edmund Hollis, UCSD
Scale bar 100 µm
Fluorogold
Fluorogold
Naumann et al. 2000
Ling Wang, UCSD
Cell filling
Viruses
Choosing the Right Tracer
Transgenic “Golgi” stains

GENSAT
 Objective: generate BAC-transgenic mice expressing GFP or CRE under the control of a gene specific promoter
 In situ Hybridization
 Emulsion Autoradiograpy
 Double labeling

Blurton-Jones et al
Blurton-Jones et al

Multiplex mRNA detection
Dave Kosman (Ethan Bier and Bill McGinnis labs, UC San Diego)
http://superfly.ucsd.edu/%7Edavek/images/quad.html
Immunohistochemistry
 Detection Methods
 TSA

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The Athlete’s Knee



The Athlete’s Knee
Presentation by:
John R. (Trey) Green, III, MD
University of Washington
Sports Medicine Clinic
206-543-1552

Anterior Knee Anatomy
* Superficial fascia
* Quadriceps muscle group
* Patella
* Synovium / plicae
* Bursae

Anterior Knee Anatomy
* Quadriceps muscle group
o Rectus femoris
o Vastus medialis
o Vastus lateralis
o Vastus intermedius

Quadriceps Muscle Group
* Vastus medialis
o Larger, and more distal insertion than vastus lateralis
o Oblique distal fibers (VMO)

Patella Articular Surface

* Thickest articular cartilage in the body (5mm)
* 25% non articular (inferior pole)

Anterior Knee Anatomy

* Bursae
o Occur to assist tissue gliding
o Variable location

Patellofemoral Biomechanics

* Patella function
o Act as a fulcrum to increase the lever arm of the quadriceps muscle

Resultant Force on the Patella

* Compression
* 2-3 x body weight
* Maximum force at 70-80 degrees of flexion

Q Angle

* Angle between the quadriceps tendon and patella tendon in full extension

Anterior Knee Pain History
* Pain
* Instability
* Catching
* Crepitation
* Weakness
* Swelling

Physical Examination

* Gait

Physical Examination

* Limb length

Physical Examination
* Compartment assessment (crepitation)
* Observation
Effusion
Prepatellar Bursal Fluid
* Range of Motion (ROM)
* Anterior knee
* Patellar position
* Patellar tracking
* Muscle tone/bulk
* Thigh circumference
* Sitting
* Lying
* Hip abductor strength
* Prone quadriceps tightness

Radiologic Examination
Rosenberg View
Merchant View
Measuring Merchant’sView
Anterior Knee Pain Treatment
* Rehab with therapist
Anterior Knee Pain Treatment
* Refer to Orthopaedist

Assessment of Meniscus, Ligament and Articular Cartilage Injuries
* Most require orthopaedic consultation
History
Pain Location
Meniscus Tears
* Meniscus tears are common
* Rapid flexion with rotation is most common mechanism
* A history of mechanical symptoms and joint line pain and tenderness suggests meniscal tear
Meniscus Tear Types
Meniscus Tears
* Arthroscopy is the gold standard for diagnosis and treatment
* Basic principles of meniscus surgery are:
o Conserve meniscal tissue
o Remove abnormal tissue
o Prevent further tear propagation
o Repair when possible
Articular Cartilage Injury
* Limited intrinsic repair capability
* Likely to eventually progress to arthrosis
* History of pain with recurrent effusions may indicate cartilage lesion
Articular CartilageTreatment Options
Medial Collateral Ligament
Beware Co-existing ACL or PCL Injury
Lateral Sided Ligament Injury
ACL Tear
PCL Tears
Knee Physical Exam
Physical Examination
Collateral Ligament Testing

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Blood Brain Barrier: Structure, Function and Bypass by Microorganisms



Discovery
What is the Blood Brain Barrier?
Structure of Blood Brain Barrier
Integrity of BBB
Astrocyte end feet
Tight Junctions between BMEC
Claudin
Occludin
Barrier Function of Occludin and Claudin
Junction Adhesion Molecules:
BMEC intercellular space
Barrier function of JAM
Cytoplasmic accessory proteins
Membrane associated guanylate kinase-like proteins (MAGUKS)
Adherens Junction
Pericytes
Astrocyte end feet
Circumventricular organs
Circumventricular organ functions:
Normal BBB transport
Factors produced by astrocytes
Glutamate,
Aspartate
Taurine
ATP
Endothelin-1
NO
MIP-2
Tumor necrosis factor alpha TNF-α
Interleukin beta IL-β
Bradykin
5HT
Histamine
Thrombin
UTP
UMP
Substance P
Qionolonic acid
Platelet activating factor
Free radicals
E. Coli model
Physical damage of BBB
Ligand receptor interactions followed by host cell actin cytoskeletal rearrangements
Transcellular transport while maintaining integrity of BMEC
Physcial damage of BBB
Conclusion
References

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21 October 2010

Cool NUCLEUS 3D Medical Animation




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HIV Replication 3D Medical Animation



HIV Replication 3D Medical Animation 


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11 July 2010

Hematology Presentations



Monoclonal Gammopathies

Hypomethylation:Turning on silenced genes and silencing the critics?

Aurora Kinases As  Anti-Cancer Targets

Bleeding Disorders

Renal Disorders in Multiple Myeloma Hematology Grand Rounds

Management of AMI in old patient

Adjuvant Therapy for NSCLC

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05 July 2010

Procedures Consult of MDConsult



Procedures Consult of MDConsult

What's Procedures Consult?
A medical procedures reference that helps physicians reduce potential medical errors and complications by providing information and resources to high-risk/high-volume procedures as well as medical procedures performed infrequently, but are critical to a patient's safety.

Centered as a medical resource, Procedures Consult is tailored to address the needs of medical personnel. Its contents are:

1. High quality videos with accurate procedures
2. Developed in conjunction with the US’s top medical institutions
3. Edited by medical professionals from esteemed medical facilities

Who Requires Procedures Consult?
Medical procedures videos from Procedures Consult address the needs of:
1. Physician/Resident/Student
2. The Educator
3. The Purchaser

Launch Features
Procedures Consult launches with content targeted at 3 major medical fields, with more than 160 in depth medical procedure videos that are developed in conjunction with the US’s top medical institutions and leveraging on Elsevier’s leading reference texts.
1. Anesthesia Module (34 procedures)
2. Emergency Medicine Module (50 procedures)
3. Orthopaedic Module (39 procedures)
4. Internal Medicine Module (42 procedures)

And more.

http://www.proceduresconsult.com/medical-procedures/

Now free trial for 30 days.

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21 May 2010

Cutaneous Fungal Infections



Cutaneous Fungal Infections
* Dermatophytosis - "ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes.
* Dermatomycosis - more general name for any skin disease caused by a fungus.

THE SKIN PLANTS
* Etiological agents are called dermatophytes - "skin plants". Three important anamorphic genera, (i.e., Microsporum, Trichophyton, and Epidermophyton), are involved in ringworm.
* Dermatophytes are keratinophilic - "keratin loving". Keratin is a major protein found in horns, hooves, nails, hair, and skin.
* Ringworm - disease called ‘herpes' by the Greeks, and by the Romans ‘tinea' (which means small insect larvae).

Infections by Dermatophytes
* Severity of ringworm disease depends on (1) strains or species of fungus involved and (2) sensitivity of the host to a particular pathogenic fungus.
* More severe reactions occur when a dermatophyte crosses non-host lines (e.g., from an animal species to man). Among dermatophytes there appears to be a evolutionary transition from a saprophytic to a parasitic lifestyle.
o Geophilic species - keratin-utilizing soil saprophytes (e.g., M. gypseum, T. ajelloi).
o Zoophilic species - keratin-utilizing on hosts - living animals (e.g., M. canis, T. verrucosum).
o Anthropophilic species - keratin-utilizing on hosts - humans (e.g., M. audounii, T. tonsurans)

Clinical manifestations of ringworm infections are called different names on basis of location of infection sites
* tinea capitis - ringworm infection of the head, scalp, eyebrows, eyelashes
* tinea favosa - ringworm infection of the scalp (crusty hair)
* tinea corporis - ringworm infection of the body (smooth skin)
* tinea cruris - ringworm infection of the groin (jock itch)
* tinea unguium - ringworm infection of the nails
* tinea barbae - ringworm infection of the beard
* tinea manuum - ringworm infection of the hand
* tinea pedis - ringworm infection of the foot (athlete's foot)

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Hyponatremia and Hypernatremia



Hyponatremia and Hypernatremia
By:Conor Gough, HO – III

Hyponatremia
* Defined as sodium concentration < 135 mEq/L * Generally considered a disorder of water as opposed to disorder of salt * Results from increased water retention * Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia * Thus, in most cases, some impairment of renal excretion of water is present Causes * Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level * Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels * Causes of Hyponatremia can be classified based on either volume status or ADH level o Hypovolemic, Euvolemic or Hypervolemic o ADH inappropriately elevated or appropriately suppressed ADH suppresion ADH elevation

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Monocyte / Macrophage Disorders



Monocyte / Macrophage Disorders
Northeast Regional Medical Center/KCOM

Granuloma Annulare
* Localized
* Generalized
* Macular
* Deep
* Perforating
* In HIV
* In Lymphoma
* Common, Idiopathic, all races
* 50% patients IgM and C3 in vessels
* LCV changes sometimes seen
* Suggests Ab mediated vasculitis
* Common in HIV patients
* EBV sometimes found
* Occurs in resolved lesions Zoster

GA - Histology
Interstitial GA
* Upper dermis
* “Skip areas”
* Mucin
* Deep dermis, subQ
* No “skip” areas
* No mucin

Localized GA
* Young adults
* Acral
* Annular, scalloped
* White or pink flat topped papules spread peripherally
* 75% clear in 2 yrs
* 25% last 8 yrs
Diffuse GA

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30 April 2010

The BioArtificial Liver



The BioArtificial Liver
By:Susana Candia
Jahi Gist
Hashim Mehter
Priya Sateesha
Roxanne Wadia

Biology of the Liver
Left lobe
Right lobe
Kidneys
Gallbladder
Falciform Ligament
Inferior Vena Cava
Abdominal Aorta

What does the Liver do?
Among the most important liver functions are:
* Removing and excreting body wastes and hormones as well as drugs and other foreign substances
* Synthesizing plasma proteins, including those necessary for blood clotting
* Producing immune factors and removing bacteria, helping the body fight infection

Other important but less immediate functions include:
* Producing bile to aid in digestion
* Excretion of bilirubin

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Renal Replacement Therapy



Renal Replacement Therapy

* What is it?
* How does it work?
Where did it come from?
History of Pediatric Hemofiltration
Mechanisms of Action: Convection
* Hydrostatic pressure pushes solvent across a semi-permeable membrane
* Solute is carried along with solvent by a process known as “solvent drag”
* Membrane pore size limits molecular transfer
* Efficient at removal of larger molecules compared with diffusion
* Solvent moves up a concentration gradient
* Solute diffuses down an concentration gradient

Mechanisms of Action: Diffusion
Semi-permeable Membranes
o Urea
o Creatinine
o Uric acid
o Sodium
o Potassium
o Ionized calcium
o Phosphate
o Almost all drugs not bound to plasma proteins
* Allow easy transfer of solutes less than 100 Daltons

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Renal Replacement Therapy



Renal Replacement Therapy
Trauma Conference
By:Amanda Wheeler, MD

Principles
4 Main Modalities in ICU
* HD
* PD
* CVVH
* CVVHD

Definition of Terms
* SCUF- Slow Continuous Ultrafiltration
* CAVH- Continuous Arteriovenous Hemofiltration
* CAVH-D- Continuous Arteriovenous Hemofiltration with Dialysis
* CVVH- Continuous Venovenous Hemofiltration
* CVVH-D- Continuous Venovenous Hemofiltration with Dialysis

Indications for Continuous Renal Replacement Therapy
* Volume Overload
* Electrolyte Imbalance
* Uremia
* Acid-Base Disturbances
* Drugs

Hemodialysis vs Hemofiltration Membrane

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29 April 2010

Bacteria Pathogenicity Ability to Cause Infection



Bacteria Pathogenicity Ability to Cause Infection

Infectious Diseases
* Encounter-bug meets host (reservoir)
* Bug adheres to host
* Entry-bug enters host
* Multiplication- bug multiplies in host
* Damage to host
* Outcome- bug or host wins or
* Coexist- chronic infection

Reservoir
* Exposure to microbe
Virulence Factors
Adherence
* Prevent infection
* Influenza changes adhesions over time
* Neisseria gonorrhoeae -variety of adhesions

Portals of Entry
* Mucous membranes
* Conjunctiva
* Skin
* Bugs have preferred portal
* C. tetani spores in soil --- anaerobic wound

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Microbial Interactions with Humans



Microbial Interactions with Humans

Types of Interactions: Symbiosis
* Symbiotic Relationships

Overview of Human-Microbial Interactions
* Pathogens
* Pathogenicity
* Virulence
* Opportunistic Pathogen

Infection Versus Disease
* Infection
* Disease

Opportunistic Pathogens

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21 April 2010

Lipids



Lipids
By: Henry Wormser, Ph.D.

Introduction
* Definition: water insoluble compounds
+ Most lipids are fatty acids or ester of fatty acid
+ They are soluble in non-polar solvents such as petroleum ether, benzene, chloroform
* Functions
+ Energy storage
+ Structure of cell membranes
+ Thermal blanket and cushion
+ Precursors of hormones (steroids and prostaglandins)
* Types:
+ Fatty acids
+ Neutral lipids
+ Phospholipids and other lipids

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Inborn Errors of Metabolism



Inborn Errors of Metabolism
By:Namrata Singh M.D

Introduction to IEM
* Usually a single gene defect that causes a block in metabolic pathways.
* Problems are because of accumulation of enzyme substrate behind the metabolic block or deficiency of the reaction product.
* In some instances the substrate is diffusible & affects distant organs & in some there is just a local effect ( lysosomal storage disease ).
* Clinical presentation is varied  mild to severe forms ( mutations even in the same gene may be different in different people ).
* Can present at any time.
* Can affect any organ system.

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Complex Carbohydrates



Complex Carbohydrates

- Know the structural components and differences between the glycoconjugate types
- Know the general biosynthetic and catabolic strategies and molecules involved
- Know the general function of each class of glycoconjugate
- Know the general biochemical principles associated with diseases resulting from defects in the catabolic pathways of the glycoconjugates

* Marks, Marks and Smith Chapter 30, primary source, Harper’s Ch 56 supersecondary source. Review Ch. 15,16 for sugar and lipid structural properties

General Biosynthetic and Catabolic Themes for Glycoconjugates
* An initial sugar residue is attached to a core protein or lipid, usually through a serine or asparagine residue.

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Sphingolipid Disorders



Sphingolipid Disorders
by:Eric Niederhoffer
SIU-SOM

Sphingolipids (phospho- or glycolipids)

General Structure
Gangliosidoses
Generalized gangliosidosis
Tay-Sachs disease
Niemann-Pick disease
Metachromatic leukodystrophy
Krabbe’s disease
Gaucher’s disease
b-galactosidase

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11 April 2010

Infectious Diseases of the Respiratory System



Infectious Diseases of the Respiratory System

Infections of the Respiratory tract
* Most common entry point for infections
* Upper respiratory tract
* Lower respiratory tract


Protective Mechanisms
Normal flora: Commensal organisms
* Limited to the upper tract
* Mostly Gram positive or anaeorbic
* Microbial antagonist (competition)

Other Protective Mechanisms
* Nasal hair, nasal turbinates
* Mucus
* Involuntary responses (coughing)
* Secretory IgA
* Immune cells

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Anatomy of Respiratory System



Anatomy of Respiratory System

Organization and Functions of the Respiratory System
* Consists of an upper respiratory tract (nose to larynx) and a lower respiratory tract ( trachea onwards) .
* Conducting portion transports air.
- includes the nose, nasal cavity, pharynx, larynx, trachea, and progressively smaller airways, from the primary bronchi to the terminal bronchioles

* Respiratory portion carries out gas exchange.
- composed of small airways called respiratory bronchioles and alveolar ducts as well as air sacs called alveoli

Respiratory System Functions
* supplies the body with oxygen and disposes of carbon dioxide

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