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| Dr. James G. Colson, Research Director |
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PLE Symposium
In September we held the first ever Protein-losing Enteropathy Symposium at the Marriott Inn in Amherst, NY. This Symposium brought together, for a two-day meeting, Scientific and Clinical professionals to discuss the origins and possible cures for this dreadful syndrome.
A question on many minds is that it is rather amazing to the lay person that after thirty years of study, we still don't even know the cause of PLE, the site of initiation, or know of any reliable cure. Part of the problem is that most hospitals only see several new patients each year. But the real problem is that the human physiology is incredibly complex with feedback loops, most of which we are just beginning to understand.
Let me take, as an example of such a feedback loop, the flow of oxygen to all parts of the body when there is an injury. Evolution says that oxygen flow to the brain is more important than to the stomach. Under stress, thinking is the most important function. Our physiology reduces oxygen flow to the stomach and sends most of the oxygen to the brain by mechanisms just being postulate. Sounds good and very seductive, but could be completely wrong! Feedback lops are all throughout your body regulating most functions. Unfortunately, we truly understand few in the complex area of PLE.
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For starters, we ask a simple question: if protein is being pushed into the tissue and being returned by the lymphatic system every day in every person (sort of a sub-clinical PLE) why does it take a different path in about five percent of patients who have had the Fontan operation? Further, why does PLE go away in one quarter of all PLE Patients? Further yet, why does PLE start within weeks in some children and years in others? Unfortunately, there are only explanations and theories.
We laid out this symposium to try to answer some of the above questions or at least to see if some pathway can be safely ignored.
The Symposium was structured to have any of the current theories and explanations discussed in physiological terms by experts, first. Then we will over clinical studies. Finally, we will cover non-Fontan PLE and some activities to lead us into the future.
We started the flow of Lectures by discussing the Fontan opeation istelf, the Fontan blood circulation, flow through the microvascular system, cardiovascular barrier integrity, and genetic defects of glycosylation.
This latter area sparked interest. A discussion period which focused on seeing if any of these above concepts where light on the clinical picture. This was followed by clinical studies of the only current treatments; namely the use of heparin, octreotide, prednisone ( a steroid) and observations on mesenteric blood flow restrictions during PLE.
Each clinical method has strengths and weaknesses. More studies are needed for a true breakthrough. The possible role of nitric oxide and the immune system closed the day. Neither had hard enough data to support their case. Another day may lead to a different conclusion. The mesenteric flow changes, noted above, clearly are a solid clue. A discussion period on the previous day lectures trying to pull out any nuances or clues started the Saturday morning session. Two talks on the possible central role of the intestine in PLE, one on a genetic PLE in dogs and one on the pathology of PLE followed. Finally, two talks were given on how to carry out future studies and setting up a PLE registry.
A final wrap-up discussion led to the conclusion that work should be carried out in four areas:
1. Genetic errors in glycoprotein synthesis are clearly one potentially unique approach. Dr. Freeze found PLE in children with a measurable genetic defect, but had never had a heart surgery, particularly no Fontan operation. They stopped PLE by simple administration of a common sugar-mannose. Our PLE Board has funded this program.. Dr. Rychik will provide blood samples for analysis by Dr. Freeze.
2. Reduced cardiac flows after the Fontan is another worthy project. Dr. Rychik can provide a 50-60 patient cohort for careful analysis by a series of tests. Much work has been done on PLE patients, but never done in one institution. Data from different sites using different tests is fraught with danger. This testing will also be the first, which includes non-PLE Fontan patients as controls Our Board will fund this effort also.
3. Inflammation may be a cause, or at least "trigger" for PLE. The virtue of this work is that we are good at treating inflammations with antibiotics, etc. Some work has been done in Japan, but seems more word of mouth, but not published yet. Dr. Schmid-Schonbein will be contacted for a proposal.
4. Mesenteric resistance noted above is an observation, not a physiological mechanism. Micro vascular permeability is probably the fundamental site PLE. We need a better study to see if we can find the cause of the resistance. Dr. Baldwin is considering such a study.
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| International PLE Symposium, Buffalo, NY |
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PLE Symposium
March 28, 2003
Dr. James G. Colson
FRIDAY
8:00 Welcome/Symposium Flow Jean-Michel Roland, M.D. Children's Hospital Buffalo
8:30 The Fontan Operation Daniel Pieroni, M.D. Children's Hospital Buffalo
9:15 Errors in Glycosylation Hudson Freeze, Ph.D. Burnham Institute
9:45 BREAK
10:15 The Lymphatic circulation David Zawieja, Ph.D. Texas A&M College of Medicine
10:45 Current theories and Discussion Robert Gingell, M.D.et al. Children's Hospital Buffalo
12:00 LUNCH Marriott Hotel
1:30 Portal system and PLE Tain Yen Hsia, M.D. Johns Hopkins Hospital
2:00 Boston Study of PLE Andrew Powell, M.D. Children's Hospital Boston
2:30 New Investigations Jack Rychik, M.D. Children's Hospital Philadelphia
3:00 BREAK
3:30 PLE and the Immune system Attila Tarnok, Ph.D. Leipzig University Hospital
4:00 Immunology of PLE Stanley Schwartz, M.D. Buffalo General Hospital
4:30 Afternoon Discussion Robert Gingell, M.D.,et al. Children's Hospital Buffalo
6:30 DINNER Marriott Hotel
SATURDAY
8:00 Progress from Yesterday Jean-Michel Roland, M.D. Children's Hospital Buffalo
8:30 Pathology Studies of PLE Saeeda Siddiqui, M.D. Children's Hospital Buffalo
9:00 Statistics of finished studies Linda Duffy, Ph.D. Children's Hospital Buffalo
9:30 Inflammatory Bowel Disease Simon Murch Ph.D. University College London
10:00 BREAK
10:30 Final Discussion Period Robert Gingell, M.D.et al. Children's Hospital Buffalo
12:00 LUNCH Marriott Hotel
The SUNY at Buffalo (UB) School of Medicine and Biomedical Sciences
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