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Re: PSC blues.

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Yes - you're right Dave - I've had the PSC blues for a long time. I'm honoured that my message elicited a response on your well-known creative side in an artistic direction. A man of many parts! While your poem might not win a poetry prize it very neatly encapsulates most of the major questions in this very frustrating disease. I wouldn't be surprised if you could play the guitar and sing - in which case you could release PSC blues on a CD. (PSC Partners Medical Ditties Inc.). We probably have hidden talent in the group and could form a backing choir.

More seriously I wonder why any young hepatologist would want to be drawn into researching PSC and PBC. Fortunately there are some. What may not be realised is that much of the medical literature on PSC which we read today is a rehash of articles published in the 1980's and 90's which I was busy reading in that medical library. I made copious notes on cards - 200 of them, which I still have; and reading them again it's pretty clear that we haven't gone very far. One of the major themes of those decades was the great promise held out by Urso. We're still waiting for the fulfilment.

Ivor

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Hi Ivor;

Trust me, you would not want to either hear me sing or play the

guitar!

I think part of the problem with the lack of progress in PSC over

the last 20 - 3O years is that there hasn't been a large enough pool

of patients and non-affected family members to study in one

centralized database. Much of the recent progress in inflammatory

bowel diseases (in terms of its genetic basis at least) has been

because of large-scale projects with large numbers of patients,

facilitating genome-wide searches for susceptibility genes. They are

now beginning to identify sub-groups of IBD patients with different

susceptibility genes. This promises the opportunity to begin to

treat different patients with different therapies, based on genetic

information, see for example:

___________________

Expert Opin Pharmacother. 2006 Aug;7(12):1591-602.

Genetic variants and the risk of Crohn's disease: what does it mean

for future disease management?

Torok HP, Glas J, Lohse P, Folwaczny C.

Department of Surgery Innenstadt, Ludwig-Maximilians University,

Nussbaumstrasse 20, D-80336 Munich, Germany. Helga.Toeroek@...-

muenchen.de

Genetic research in inflammatory bowel disease, especially in

Crohn's disease, has made significant progress during recent years.

There have been > 10 total genome scans that have been performed,

and susceptibility loci on several chromosomes have been identified.

Together with candidate gene studies, these scans have led to the

identification of several susceptibility genes, with CARD15 being

the most important. These genetic data have already provided

important insights into the pathophysiology of inflammatory bowel

disease and are stimulating future research. On the other hand,

genotype-phenotype associations have illustrated the heterogenic

nature of the disease. Although the clinical application of this

knowledge is so far limited, there is significant optimism that an

individual management of patients based on genetic data will be

possible in the near future.

PMID: 16872262

_____________________

PSC will probably prove to be a mixture of different diseases with

different causes ... perhaps with different susceptibility genes,

different environmental triggers, and different autoimmune

involvement? Already we see sub-groups, for example with elevated

IgG4 (which may respond to corticosteroids?), with overlap with

autoimmune hepatitis, or with only small-duct involvement. This is

why I am excited about the STOPSC registry. It may eventually permit

identifying several different PSC susceptibility genes with

treatment taylored to each type. I am a firm believer that if IBD

has a genetic basis (albeit complex), then PSC/IBD must also have a

genetic basis, and understanding the genes involved will eventually

point to the underlying pathophysiology.

Best regards,

Dave " Muddy "

(father of (21); PSC 07/03; UC 08/03)

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Hi Ivor;

Trust me, you would not want to either hear me sing or play the

guitar!

I think part of the problem with the lack of progress in PSC over

the last 20 - 3O years is that there hasn't been a large enough pool

of patients and non-affected family members to study in one

centralized database. Much of the recent progress in inflammatory

bowel diseases (in terms of its genetic basis at least) has been

because of large-scale projects with large numbers of patients,

facilitating genome-wide searches for susceptibility genes. They are

now beginning to identify sub-groups of IBD patients with different

susceptibility genes. This promises the opportunity to begin to

treat different patients with different therapies, based on genetic

information, see for example:

___________________

Expert Opin Pharmacother. 2006 Aug;7(12):1591-602.

Genetic variants and the risk of Crohn's disease: what does it mean

for future disease management?

Torok HP, Glas J, Lohse P, Folwaczny C.

Department of Surgery Innenstadt, Ludwig-Maximilians University,

Nussbaumstrasse 20, D-80336 Munich, Germany. Helga.Toeroek@...-

muenchen.de

Genetic research in inflammatory bowel disease, especially in

Crohn's disease, has made significant progress during recent years.

There have been > 10 total genome scans that have been performed,

and susceptibility loci on several chromosomes have been identified.

Together with candidate gene studies, these scans have led to the

identification of several susceptibility genes, with CARD15 being

the most important. These genetic data have already provided

important insights into the pathophysiology of inflammatory bowel

disease and are stimulating future research. On the other hand,

genotype-phenotype associations have illustrated the heterogenic

nature of the disease. Although the clinical application of this

knowledge is so far limited, there is significant optimism that an

individual management of patients based on genetic data will be

possible in the near future.

PMID: 16872262

_____________________

PSC will probably prove to be a mixture of different diseases with

different causes ... perhaps with different susceptibility genes,

different environmental triggers, and different autoimmune

involvement? Already we see sub-groups, for example with elevated

IgG4 (which may respond to corticosteroids?), with overlap with

autoimmune hepatitis, or with only small-duct involvement. This is

why I am excited about the STOPSC registry. It may eventually permit

identifying several different PSC susceptibility genes with

treatment taylored to each type. I am a firm believer that if IBD

has a genetic basis (albeit complex), then PSC/IBD must also have a

genetic basis, and understanding the genes involved will eventually

point to the underlying pathophysiology.

Best regards,

Dave " Muddy "

(father of (21); PSC 07/03; UC 08/03)

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Share on other sites

Guest guest

Hi Ivor;

Trust me, you would not want to either hear me sing or play the

guitar!

I think part of the problem with the lack of progress in PSC over

the last 20 - 3O years is that there hasn't been a large enough pool

of patients and non-affected family members to study in one

centralized database. Much of the recent progress in inflammatory

bowel diseases (in terms of its genetic basis at least) has been

because of large-scale projects with large numbers of patients,

facilitating genome-wide searches for susceptibility genes. They are

now beginning to identify sub-groups of IBD patients with different

susceptibility genes. This promises the opportunity to begin to

treat different patients with different therapies, based on genetic

information, see for example:

___________________

Expert Opin Pharmacother. 2006 Aug;7(12):1591-602.

Genetic variants and the risk of Crohn's disease: what does it mean

for future disease management?

Torok HP, Glas J, Lohse P, Folwaczny C.

Department of Surgery Innenstadt, Ludwig-Maximilians University,

Nussbaumstrasse 20, D-80336 Munich, Germany. Helga.Toeroek@...-

muenchen.de

Genetic research in inflammatory bowel disease, especially in

Crohn's disease, has made significant progress during recent years.

There have been > 10 total genome scans that have been performed,

and susceptibility loci on several chromosomes have been identified.

Together with candidate gene studies, these scans have led to the

identification of several susceptibility genes, with CARD15 being

the most important. These genetic data have already provided

important insights into the pathophysiology of inflammatory bowel

disease and are stimulating future research. On the other hand,

genotype-phenotype associations have illustrated the heterogenic

nature of the disease. Although the clinical application of this

knowledge is so far limited, there is significant optimism that an

individual management of patients based on genetic data will be

possible in the near future.

PMID: 16872262

_____________________

PSC will probably prove to be a mixture of different diseases with

different causes ... perhaps with different susceptibility genes,

different environmental triggers, and different autoimmune

involvement? Already we see sub-groups, for example with elevated

IgG4 (which may respond to corticosteroids?), with overlap with

autoimmune hepatitis, or with only small-duct involvement. This is

why I am excited about the STOPSC registry. It may eventually permit

identifying several different PSC susceptibility genes with

treatment taylored to each type. I am a firm believer that if IBD

has a genetic basis (albeit complex), then PSC/IBD must also have a

genetic basis, and understanding the genes involved will eventually

point to the underlying pathophysiology.

Best regards,

Dave " Muddy "

(father of (21); PSC 07/03; UC 08/03)

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