27 September 2009

From mice To Men



From mice To Men

Jumpstarting A Laboratory Research Career
December 6, 2007
By: Elizabeth M. Jaffee, M.D.
The Dana and Albert “Cubby” Broccoli Professor of Oncology


Issues to Consider
* Stay where you trained or go elsewhere
* Identifying mentors
* Deciding on a research focus
* Leveraging small grants, getting the big one
* Building a team to work for you
* Balancing the work versus home life

Should you stay where you trained or should you take your first job at another institution?
* Pros for staying
o Implies you have a supportive mentor
o Implies you have a project of interest to others in your institution
o Experience with the institutional systems
o Experience with who might be good colleagues
* Start Up Time Is Shorter
* Pros for leaving
o Cuts the apron strings so that you are not in competition with your mentor at same place
o Likely to get more space and resources due to negotiations
o Likely able to get good students with less competition in your field
* No Identity Complex

Identify a mentor(s) for the most difficult stage in your career

* Cheer leader, promoter, encourager
* Sounding board for fine tuning ideas
* Devil’s advocate whose not afraid to give you the opposite view
* Editor of paper’s, grants, and presentations
* Guidance counselor to help you navigate through tough issues
* Referral Agent who sends you qualified student/postdoctoral fellow applicants
* Introduces you to leaders in your field
Your parent in the workplace

Develop A Five-Year Plan
Time interval goal between Assistant and Associate Professor
* What research questions do you want to focus on?
* What do you need to get you to where you want to be at 5-years
* Is it feasible now? At 1, 2, 3, and 4 years later?
* Revisit each year with your mentor to make sure you are on track
* How many grants and papers do you plan to submit?

Considerations in choosing how to focus your research
* Choose areas that make you want to come to work
o Desire, Desire, Desire!
* Choose a 5-year plan that will help you develop an identity separate from your mentor’s
* Consider several related areas - one high risk and and one or more low risk
* Choose areas that have more than one funding source

Grants: If only it were the 1990’s Again!
* Apply for more than one
o Can submit same grant to several funding agencies or similar ones that overlap
* Apply for career development grants first
* Pursue institutional grants and foundations if appropriate
* Spend 3 or more months writing your first grant
o Have a draft available 1-2 months before due date
o Ask mentor and other colleagues to review
o Have a scientist in a related but different field read the grant for clarity of presentation of ideas
* Go for the R01 by the end of the 5-year plan

Building a Team That Works For You, Literally!
* Learn to lead
o You will make mistakes - learn from them
o Take leadership development courses
o Listen to your team
o Show trust and faith in your team members!
o Mistakes are made by all of us. Be forgiving and continue to trust.
o Don’t let emotions or sense of insecurity get in the way of doing the right thing for your team (we all have this starting at all stages of our career).
* Lead by example
* Identify individuals you can influence
o Make sure they have the personality to take direction from you
o Make sure they have qualities you value
o Make sure you can lead them to be the best they can be

Get the right people on the bus!
Key Point
* There are no special deals when it comes to people resources. Make sure they have the right experience to contribute to your team

* People resources are the single most important ingredient to success
* Develop a healthy work environment
* If you can’t do it on your own, hire someone to be your lab ambassador
* Get as many references as possible
* Ask everyone in your group and others with successful labs to interview candidates
* Reward valued team members with lunches, meetings, etc.
* Provide career development to your valued team members.

Healthy environments attract more good people to help you build and maintain a productive team!
Develop a reputation for leadership and fairness early!
You Are Your Best Advocate
* Promote yourself
o Discuss ideas with others
o Let colleagues know about your successes
o Offer to participate in meetings, etc
o Let colleagues know you are willing and available
* Let your boss know of your important successes
o Grant awards
o Accepted papers
o Abstract acceptances of high impact
* Develop a national reputation
o Get invited to national meetings by telling colleagues of interesting work
o Offer to present locally and at national meetings for visibility
o Get introduced to prominent individuals in your field

Senior scientists delight in interacting with enthusiastic, intelligient, honest, and creative young scientists who are the next leaders!

Women still have special issues (I can tell some stories!)
* My graduate student’s experience
* Women in science (am I the only one?)
* Postdoctoral fellows and junior faculty I know who get taken in by charming individuals disguised as mentors
* Our generation of men and women are making a difference

Pearls of Advise On How To Succeed in A Man’s World (from The Godfather)
* Just when I thought I was out, they pulled me back in!!!
* Keep your friends close, and your enemies closer!!!
* It ain’t personal, just business!!!

If you are going to fight for something, pick the right battles!
You can’t possible win them all!
If you don’t like someone, nominate them for something important!
If someone does something bad to you, don’t allow your emotions
to get in the way of how you deal with the situation!

HARDWORK
FOCUS
DETERMINATION
Don’t forget about a home life!
Physician-Scientist, Wife, and Mom
* Roadmap to successful

Inspiration
Role Models or Mentors
Hardwork
Focus
Determination
A balancing act!
Integrating a successful career with a home life
The road to success in anything is easier when you have a supportive partner!
Kids are the ultimate reminders of what is important in life!
Animals can be less demanding but loving substitutes!

Jumpstarting A Laboratory Research Career.ppt

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Insect Sting Allergy and Venom Immunotherapy



Insect Sting Allergy and Venom Immunotherapy
By: David B.K. Golden, M.D.
Johns Hopkins University, Baltimore


History of Reaction to Insect Stings (Skin Test Positive Patients)

No reaction
Large Local
Cutaneous Systemic
Anaphylaxis

Severe swelling 24 hrs after a sting should be treated with:
A. Antibiotics C. Antihistamine E. Epinephrine
B. Prednisone D. Venom immunotherapy

Venom immunotherapy:
A. Is not necessary (“He’ll outgrow it”) B. Is dangerous
C. is only partially effective D. Is forever E. None of the above

Diagnosis of Insect Sting Allergy (Indications for Venom Immunotherapy)
Symptoms and Signs of Insect Sting Anaphylaxis in Adults and Children
Symptoms or Sign
Cutaneous only
Urticaria/angioedema
Dizziness/hypotension
Dyspnea/wheezing
Throat tightness/
Hoarseness
Loss of consciousness

Epidemiology of Venom Allergy
* History of systemic reaction in 0.5%-3.0% of the population
* Positive venom skin test or RAST in 15%-25% of the population.
* Transient positive skin test or RAST may occur after uneventful sting.
* Presence of IgE venom antibody not necessarily predictive of clinical reactivity.

Correlation of Yellow Jacket Venom
RAST and Skin Tests
History Positive Patients with Negative Venom Skin Tests
Possible explanations:
Not true allergic reaction (no objective signs)
Allergy “outgrown”
Mastocytosis (~1 % of insect allergic patients)
Not detected:
Diagnostic Venom Test Reactivity after Systemic Sting Reaction
Venom Skin Test / RAST in History Positive Patients
Total history positive patients screened:
Diagnosis of Insect Allergy in Patients With Positive History (Systemic)
Skin test positive
ST negative /
Low Risk Sub-Groups of Patients With Positive Venom Skin Tests
Insect Sting Allergy in Children
Summary Of Sting Reactions
Natural History of Large Local Reactions
Repeat Systemic Reaction In Sting Allergic Patients
Risk of Systemic Reaction in
Untreated Skin Test Positive Patients
Controlled Trial of Venom Immunotherapy
Venom Immunotherapy Treatment Protocols
Dose Response of Venom Immunotherapy
Premedication During Venom Immunotherapy
Venom-IgE and Skin Test During
and After Venom Immunotherapy
Discontinuing Venom Immunotherapy:
Reported Studies and Criteria
Discontinuing Venom Immunotherapy

Insect Sting Allergy and Venom Immunotherapy.ppt

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Allergy Grand Rounds



Allergy Grand Rounds
By:Sarbjit S. Saini, M.D.
JHAAC

Chief complaint
* 13 yr old male referred in June 2004 for evaluation of severe chronic urticaria
* Referred by pediatric allergist in VA
* Significant illnesses:
o include Type I DM for 2.5 yrs
o ADHD
o mood disorder

History of Present Illness-I
History of Present Illness-II
History of Present Illness-III
Other atopic history
* No history of eczema or food allergy
* Allergic rhinitis symptoms
* Exercise-related asthma age 9 treated with prn albuterol prior to activity
* Reported qhs cough, but denied wheezing
Medications
* Zoloft, 50 mg qd**
* Oxcadazepine (Trileptal) 300 mg/600 mg **
* Adderall 30 mg bid
* Quetiapine (Seroquel) 200 mg qd
* Fexofenadine 180 mg qd ( off 1 wk)
* Cetirizine 10 mg qd ( off 1 week)
* Cyclosporine 100 mg bid (off 1 wk)
* Humulin 7 U/4 U, Humulin R 5 U/ 4 U
* Epipen, Albuterol

Past Medical History
* Type I DM for 2.5 yrs
* ADHD
* Mood disorder, possible bipolar
o exacerbated by steroids
o suicidal ideation due to urticaria
* Chicken pox as child
* Salivary gland surgery
* Normal birth history, negative history of other infections
Family History
* Younger Sister with eczema
* PGM with asthma
* Paternal cousins with asthma
Environmental Hx
* Apt dweller x 5 yrs
* Dog since 1999
* 3 hamsters

Social Hx
* 7th grader
* Lives with mom and sister
Physical Exam
* T-99.7, HR-121, BP-109/75, HT-5, WT-125,RR-22
* General: no obvious pubertal signs,central obesity, moon facies
* HEENT: “allergic shiners”,erythematous nasal mucosa, prominent turbinates
o Normal TMs, oropharynx, neck
* Resp: CTA, normal I:E ratio, CV: nl S1, S2 tachy
* Abdomen: benign Ext: no joint swelling
* Skin: urticaria on face, arms, feet, back, chest; no pigmentation

Recent labs
* CBC-WBC 7.3 HCT-41.2, Plts-331
* HbA1C-8.6 (4-6) Jan 2004
* Negative studies: ANA, H. Pylori Ab,anti-thyroid peroxidase antibodies, WESR
* Normal C3, C4, CH50; TSH, thyroxine, T3 and T4
* RASTS- negative for crab, lobster, fish garlic and insulin

Cyclosporine related labs
* Jan 2004 reduced Hct-12.1 HB- 37.2
o CsA: 37 ng/ml trough
* March 2004 Normal studies
* June 2004
o CsA: 46 ng/ml trough
o CBC, Mg, Cr, K normal
Impression/ Recommendations
* Severe CIU/angioedema h/o significant steroids requirements
o No clear drug (insulin), food or systemic etiology
o Avoiding NSAIDs
* Consider alternate diagnoses:
o Hx of autoimmunity with Type I DM
o Rheumatologic?-joint symptoms, bruising
o Obtain a skin Biopsy to verify urticaria vs. other
+ Consider immunofluorescence

Follow-up on Recommendations
* Rheum evaluation: Repeated ANA, RF, dsDNA, ANCA, Urine and SPEP- all normal
o showed IgA of < 20, no other etiology for joints
* October 04 -Csa 100 mg qd and fexofenadine with good control
* Prednisone used only single day since 6/2004
* No skin biopsy to date- attempted
* Glucose under better control
CU in children : association with thyroid autoimmunity
* 187 CU pts (6- 18 yr) followed 7.5 yrs
* Tests: CBC, sed, Chem, Antibodies to Hep B, HSV, EBV,CMV, mycoplasma, ASO, ANA, C3, C4, Thyroid function and antibodies,Ua, chest and sinus X-rays, food skin tests, ice cube test
* Results: 8/187 antithyroid Ab (4.3%), all girls
o 3x -1.27% rate seen in pediatric population
o Much less than 14 to 33% range in adults
o 5 +ANA, 4 + family Hx of autoimmunity
Cyclosporine in Urticaria
* CBC, Mg, K, renal function q 2 wks for first 3 months, CsA levels
* Gingival hypertrophy
* BP monitoring
* Dose: 2-6 mg/kg/d similar to RA and psoriasis (2.5 mg/kg/day)
* Tx dose 8 mg/kg/d; trough levels 100 ng/ml

CsA and Urticaria-RDBCT
* 30 subjects, severe CIU unresponsive to H1 tx and positive ASST ( +HRA)
o 4mg/kg CsA (n=20) or placebo (n=10) for 4 wks
o All subjects followed for up to 20 wks, all on daily 20 mg cetirizine
* Outcome: +< 25% of baseline UAS, relapse > 75% of UAS
* Results: 8/19 + at week 4, 6 relapse wk 6
o Noted reductions in HRA and ASST

CsA in CIU:Adults
* Open trial in 35 CIU with 3(0-3)
o Low dose CsA 3 mos, 68% response (13/19) with few SEs1
* DB trial :40 pts CsA 5 mg/kg x 8 wks, then 4 mg/kg x 8 wks vs. cetirizine 10 mg/d2
o All cetirizine crossed to active CsA
o 3 pts reduced CsA for Cr rise
o On tx- 22 had relapse, 10 resolved spon 12 with H1
o Off tx- 16/40 in remission at 9 mos

Immunosuppression in Adolescents: Cyclosporin
* 80% of liver, kidney, cardiac Tx > 5 yr survivors on CsA
* Nephrotoxicity: 4-5 % in cardiac and liver
o 10% in RA dosed > 4 mg/kg avg 19 mos
* HTN (20-30%)
* Hyperlipedemia (10% of cardiac)
* Post-tx lymphoproliferative disease:5-17%
* Cosmetic-Gingival hyperplasia, hirsutism

Allergy Grand Rounds.ppt

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