Here are just some notes from different topics dicussed in the conference, we can then discuss each speperatly in seperate posts.
1- Usage of Antisense Technology to restore correct splicing... this topic was discussed under the gene correction.
Actually i am trying to read in this topic but can not grasp it 100% so i will be great if Andy would shed some light on this. But we can say that in antisense technology, synthetically-produced complementary molecules seek out and bind to messenger RNA (mRNA), blocking the final step of protein production. mRNA is the nucleic acid molecule that carries genetic information from the DNA to the other cellular machinery involved in protein production. By binding to mRNA, the antisense drugs interrupt and inhibit the production of specific disease-related proteins.
This applies mainly to thal mutation that are related to the m(RNA) and not the beta or alpha globin
2- Thalidomide derivatives increases Hb
3- Oxidative stress oxidizes proteins, lipids and DNA leading to organ failure and antioxidants are
a) Vitamin E is safe upto 600mg
b) Curcumin up to 500mg
c) N-Acetyle Cytosine
d) Fermented Papaya preparation FPP
4- Usage of Nitric Oxide in thalassemia is best studied by Doctor Gladwin in the USA ( actually this was an advice from doctor Rachmilewitz but he couldn't give me the full name
5- Labile Plasma Iron is the blood test made to see how much free iron radicles are there in the body ( actually not availale in every country )
6- In answering one of my questions about any available information about iron being overloaded in the brain, Dr. Ali Taher said that there is an ongoing study measuring this through MRI on the brain.
7- Living with low Hb does not affect mental skills or IQ unless the ''normal for the person'' changes then transfusion is then required.
8- ECG can detect signs of Pulmonary hypertension and should be done every year. Then from the age of 10 years ferriscan and T2* should be made even if the patient does not transfuse.
9-
Very important note: Having gaps in chelation is not recommended at all because in the time of this gap all the iron tend to settle in the heart and not the liver so a patient who have lots of time gaps in chelation has to check the heart iron as the liver iron overload will not be a sufficient indicator
10- We can have iron overloaded in the heart and the liver is free of iron and vice versa, that is why T2* is important to do in addition to ferriscan.
11- We can not predict heart failure but there could be some signs
a) murmurs
b) JVP
c) Low Cardiac output (CO )
d) High BNP
Heart failure could be seen in both transfused and non transfused thal. In majors through ironoverload and in intermedia through increased CO . In certain cases heart failure can be reversible and L-Carnitine is advises tobe given to major and intermedias.
12- Ca2 ( Calcium 2 ) works as a blocker to iron in the heart
13- Splenectomy is not at all advised or we should keep it as long as we can
14- Partial splenectomy is no more done in the UK as the spleen grows again
15- Post splenectomy sepsis can not be prevented by education but infections can ( A comment that i liked from one of the doctors )
16- Ironoverload distribution usually in Parathyroid, Liver, Pancreas, Thyroid, Skeletal tissue, then the brain ( can not recall where does the heart fit )
17- Role of Hepcidine in iron overload
18- I asked many of the endocrinologist about this fact, the body of the thal is usually insensitive to the growth hormone and can not use it fully though it is there in the normal range '' they said that this is true and when i asked them should we give growth hormones in order to stimulate the body to use it , all of their answers was a clear NO
19- What is monitered in growth is
a) Height velocity (very important)
b) Height sitting and standing
c) Bone Age
20) Studies show that thal girls height tend to be in the normal range while thal boys tend to be short
21) Very important to measure the spinal growth because reduced spinal growth affects height in puberty.
22) Studies found that the usage of desferal before the age of two years of age cause the spinal cord vertebra to flaten leading to a short spine but the limbs are not affected and they grow normally. This problem was not seen in children who used desferal after the age of two. That is why spinal bones measurement is important.
23) Osteoprosis causes are multi factorial and most of them are not known to doctors. Intermedias and Majors both develop Osteoprosis. Though majors have high Hb but they too develop Osteoprosis. That was one of the lectures that had a negative impact on me cause the two doctors who talked about Osteoprosis said that you can not avoid cause the reasons are unknown multi factorials. But from the known causes
a) Bone expansion
b) Hypogonadism
c) Calcium, zinc, vitamin D definciency
d) Lack of exercises
So these lectures talked more on medications rather than preventation
24) Role of Glutamate in growth
25) Intermedias are prone to
a) Leg ulcers (shortage of bloood supply to limbs)
b) PHT
c) Thrombosis
Intermedias more than 20 years should have thrombophilia screening if they have family history or had previous thrombophilia. Intermedias even children should have anticogulante medications like asprin for example. When i asked Dr. Ali Taher that giving baby asprin is not allowed except after the age of 12or 13 years to any child. He said that this is true and the other fact of high risk of thrombophilia is true too so you have to make a balance between the two risks ( the concept of choosing the best of two worset cases
)
Causes of high thromophilia rate in intermedia:
a) increased number of platletes
b) the different nature of red blood cells caused by the presence of extra alha in the blood
c) Endothelial cells injury in splenctomy leads toan increase in the production of platletes
Generally speaking most topics concerning intermedias need further studies and investigation
26) Only thing mentioned about thal minors is that they have a high risk of Oligohydramnios in pregnancy
27) Though Hb F does not release oxygen, it was found that an old man around 65 years has a homozygous thal mutation 39 who has 100% of his blood HB F and was never transfused
28) The same mutation was found in two brothers, one of them is transfusion dependant and the other is not though they have the same mutation. This leads us to a big fact that each thal patient is a completely different and independant and you can not compare two patients togather cause ther are many other factors in the body that play a role in the manifestation of the disease even with the same mutation
Hope this hepls and we can choose any of these topics to discuss seperatly
Take care
Manal