Large vessel vasculitis (LVV)- Takayasu and GCA:-
1. Thorough clinical and imaging assessment of the arterial tree when a diagnosis of Takayasu is suspected-
• MRA/PET could assist in diagnosis and document of extent of involvement but has its limitations (not widely available, operator dependant).
• Conventional angiogram is gold standard
2. In Giant cell arteritis,
• Temporal artery biopsy should be performed
• 1cm tissue length is required
• skip lesions may lead to false negative HPE
• Don’t delay treatment while waiting for biopsy. Treat first.
• If CRP/ESR is not elevated, think of another diagnosis
• USG of the temporal artery looking for vessel wall oedema was 88% sensitive and 97% specific in diagnosing GCA
3. Start steroids early and at high dose for induction of remission of LVV
• Prednisolone- 1mg/kg (max 60mg) daily
• Maintain for 1 month then taper
• Taper should not be in the form of EOD therapy which is a/w higher relapse rate
• At 3 months, steroid dose should be at 10-15mg/d
• Steroid duration could be for several years
• Must give bone protection during this period
4. Immunosuppressive agents should be considered in LVV as adjunctive therapy
• Methotrexate (20-25mg weekly)
• Azathioprine (2mg/kg/d)
• Cyclophosphamide (in steroid resistant Takayasu)
5. Monitoring of LVV- clinical and inflammatory markers
6. Use low dose aspirin in all GCA pt
7. Reconstructive surgery for Takayasu should be performed during the quiescent phase at expert centres
Thursday, February 26, 2009
Monday, February 9, 2009
Equivalent anti-inflammatory doses of different oral corticosteroids
This table takes no account of mineralocorticoid effects, nor does it take account of variations in duration of action
Prednisolone 5mg
is equivalent to betamethasone 750 mcg
is equivalent to cortisone acetate 25 mg
is equivalent to dexamethasone 750 mcg
is equivalent to deflazacort 6mg
is equivalent to hydrocortisone 20mg
is equivalent to methylprednisolone 4mg
is equivalent to traimacinolone 4mg
Prednisolone 5mg
is equivalent to betamethasone 750 mcg
is equivalent to cortisone acetate 25 mg
is equivalent to dexamethasone 750 mcg
is equivalent to deflazacort 6mg
is equivalent to hydrocortisone 20mg
is equivalent to methylprednisolone 4mg
is equivalent to traimacinolone 4mg
Wednesday, January 21, 2009
Journal Club- 21/1/2009 CIMR
The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance
Alejandro Villagra1, Fengdong Cheng1, Hong-Wei Wang1, Ildelfonso Suarez1,2, Michelle Glozak3,4, Michelle Maurin1, Danny Nguyen1, Kenneth L Wright1,4, Peter W Atadja5, Kapil Bhalla6, Javier Pinilla-Ibarz1,4, Edward Seto3,4 & Eduardo M Sotomayor1,3,4
Antigen-presenting cells (APCs) induce T cell activation as well as T cell tolerance. The molecular basis of the regulation of this critical ‘decision’ is not well understood. Here we show that HDAC11, a member of the HDAC histone deacetylase family with no prior defined physiological function, negatively regulated expression of the gene encoding interleukin 10 (IL-10) in APCs. Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells. Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses. Thus, HDAC11 represents a molecular target that influences immune activation versus immune tolerance, a critical ‘decision’ with substantial implications in autoimmunity, transplantation and cancer immunotherapy.
Alejandro Villagra1, Fengdong Cheng1, Hong-Wei Wang1, Ildelfonso Suarez1,2, Michelle Glozak3,4, Michelle Maurin1, Danny Nguyen1, Kenneth L Wright1,4, Peter W Atadja5, Kapil Bhalla6, Javier Pinilla-Ibarz1,4, Edward Seto3,4 & Eduardo M Sotomayor1,3,4
Antigen-presenting cells (APCs) induce T cell activation as well as T cell tolerance. The molecular basis of the regulation of this critical ‘decision’ is not well understood. Here we show that HDAC11, a member of the HDAC histone deacetylase family with no prior defined physiological function, negatively regulated expression of the gene encoding interleukin 10 (IL-10) in APCs. Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells. Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses. Thus, HDAC11 represents a molecular target that influences immune activation versus immune tolerance, a critical ‘decision’ with substantial implications in autoimmunity, transplantation and cancer immunotherapy.
Thursday, January 15, 2009
Humoral Immunity
Slides have been intentionally made 'wordy' to enable better understanding of the topic.
Wednesday, January 14, 2009
Journal Club- 14th January 2009 (CIMR)
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease
Maria Florencia Delgado1, Silvina Coviello1, A Clara Monsalvo1, Guillermina A Melendi1,2, Johanna Zea Hernandez1,2, Juan P Batalle1, Leandro Diaz1, Alfonsina Trento3, Herng-Yu Chang4, Wayne Mitzner4, Jeffrey Ravetch5, Jose ́ A Melero3, Pablo M Irusta1,6 & Fernando P Polack1,2,7,8
Abstract:
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.
Maria Florencia Delgado1, Silvina Coviello1, A Clara Monsalvo1, Guillermina A Melendi1,2, Johanna Zea Hernandez1,2, Juan P Batalle1, Leandro Diaz1, Alfonsina Trento3, Herng-Yu Chang4, Wayne Mitzner4, Jeffrey Ravetch5, Jose ́ A Melero3, Pablo M Irusta1,6 & Fernando P Polack1,2,7,8
Abstract:
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.
Monday, January 12, 2009
Thursday, January 8, 2009
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