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This information is designed for use by researchers and parents interested in autism and PDD. I have included numerous abstracts so you can judge for yourself the reasoning behind my approach to this very complicated disorder. Don't get bogged down in the details if you are not a clinical researcher. Glean the highlights and you will start to pick up some of our lingo as you become more familiar with the subject.
Parents of newly diagnosed children with severe development delay problems face a host of options. I have the perspective of being both a parent of an autistic child, a family practitioner, and an autism researcher. I have made the tough decisions we all have to make and lived with the consequences for my son. I take all these recommendations quite seriously. So you'll know where I am at with this I'll tell you our saga.
My son, Matthew, (currently 5 years old) was an obviously MMR injured child. We have the tests to substantiate this, but his history was typical. We now know he has antibodies to myelin (the insulation of the nerve cells), NAFP (brain cell structures), and a measles titer 15 standard deviations above normal vaccine levels. Within days of his MMR vaccine Matthew started crying all day long. He was awakened at night with terrors that took sometimes hours to calm down. He became detached, withdrawn and wild. He stopped responding to pain and couldn't tell when he hurt himself. He developed intractable diarrhea and become chronically ill. But now he is doing remarkably better. His behavioral therapists find him almost a typical child. He is still struggling with fine motor development, but has wonderful and complex speech. He is affectionate and plays with other children (once he gets to know them - which usually takes 30 minutes or so of silly behaviors until he calms down). He is hardly ever ill now and his stools are normal. He is potty trained except for nighttime wetness, which comes and goes. His treatment has been complex. He has had intense behavioral therapy, a gluten and casein free diet, IVIG, secretin, vitamins, allergy neutralization, sphingolin, auditory integration therapy, sensory integration, ear tubes for chronic otits media, physical therapy, occupational therapy, vision therapy, speech therapy, Tenex, amino acid therapy, and lots of love and prayers. I believe he needed every bit of it. Each treatment contributed some part of his progress and we are thankful to have been able to provide it for him.
Today, Matthew is full of energy and imagination. He plays with his sister. He asks me how he can help with my household chores - all spontaneously! Sometimes he still has a hard time attending to his lessons, but he is generally easily redirected. He is no longer dependent on Tenex to get through a day without meltdowns, and doesn't need anything to sleep at night. He still takes lots of vitamins, minerals and other supplements. Our hope for you is that you will see similar or better progress in your child, because of the lessons we have learned from Matthew and his care. God does work ALL things together for the good of those that love him, even a child's autism can be used to help countless others. Matthew was accepted to start kindergarten at Covenant Christian School, a private school for typical children, without autism. Praise God!
I do have to make an important disclaimer: these are general recommendations and do not constitute a doctor - patient relationship. Also, current medical knowledge is incomplete and you must keep up with new discoveries. Contact us frequently if need be. Write to the Autism Research Institute and subscribe to Dr. Rimland's monthly newsletter. It is one efficient way to stay current - they do all the work of researching the world's literature. Get a copy of the DAN! Protocol from them as well. Their address is 4182 Adams Avenue, San Diego, CA, 92116. Web Site: www.autsim.com/ari/ also www.secretin.com
The data (outcomes-based results) of all patients evaluated at the Good News Doctor center will be made available to the Autism Research Institute for research purposes only.
Part 1. How did our kids get into this mess?
While I do not have a complete answer, medical research is certainly giving us some significant clues. The State of California has been tracking autism for years and the incidence has increased by 400% in the past 12 years. Within the next few years I believe the immunological etiology (what causes it) of autism will be well documented. Here are a few clues:
1) Schizophrenia and autism have similar findings of blood and urinary opioid excesses. Reference Dr. Robert Cade, University of Florida. Schizophrenia is also associated with elevated levels of IL-2 (a chemical messenger of the immune system). I suspect autism also has increased IL-2.
2) In young children, autism is often cured or greatly helped by removal of casein and gluten: Shattock, Reichelt, Cade, Freidman. Gluten and casein have immune, as well as neurotransmitter impacts. Gluten and casein therefore have the ability to cause immune dysregulation and neurotransmitter imbalance. Fudenberg and Cade.
3) Many autistic children have a history of either frequent early ear infections or milk/formula intolerance. The frequent infections may affect sound input during critical phases in brain development. These infections may also influence the immune system in adverse ways making vaccine reactions more likely. They may further be caused by immune changes caused by vaccines. Lastly, the weakness in the immune system may be a sign of actual immune deficiency, as with IgA deficiency (seen in about 20% of autistics – Gupta). The problems with formula point to casein intolerance from an early age.
4) Many autistic children have ileolymphnoid hyperplasia or an inflammatory bowel-like disorder. Wakefield et al Lancet, Feb 28, 1997 - this seems correlated with an MMR vaccine reaction. The gut problems with autism are often extensive. Horvath at the University of Maryland has seen significant esophageal reflux problems. We know both constipation and diarrhea are common complaints in autism. Both may result from immune injury to the gut as well as neurological regulation problems. Diet also contributes to these symptoms. We do see other pathogenic causes of diarrhea on autism. Parasites, bad bacteria, and yeast may all account for GI distress. The GI neurohormones, like secretin are also important for brain function. See you really are what you eat – or maybe what your gut tells your brain after you eat.
5) Most autistic children are allergic to some foods, inhaled pollens or mold. These allergic reactions disrupt normal immune balance and alter interleukin 2 levels (again, one of my pet theories currently under investigation) exacerbating their symptoms. Interleukin-2 overproduction is implicated in schizophrenia type symptoms (as noted):
Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders.
Authors: Muller N , Ackenheil M Psychiatric Hospital, Ludwig Maximilian-University, Munich, Germany. Prog Neuropsychopharmacol Biol Psychiatry 1998 Jan;22(1):1-33
The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system. An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described. Cytokines, actively transported into the CNS, play a key role in this immune activation. It was recently observed that cytokines activate astrocytes and microglia cells, which in turn produce cytokines by a feedback mechanism. Moreover, they strongly influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. There are indications that the cascade of cytokines can be activated by neuronal processes. These findings close a theoretical gap between stress and its influence on immunity. Psychomotor, sickness behavior and sleep are related to IL-1; disturbances of memory and cognitive impairment are to IL-2, in part also to TNF-alpha. The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia, and IL-6, on depressive disorders. A characteristic pattern of cytokine actions in the CNS, including influences of the cytokines on the blood-brain barrier, seems to play a role in psychiatric disorders. This may have therapeutic implications for the future.
Food allergy and infantile autism.
Authors:
Lucarelli S , Frediani T , Zingoni AM , Ferruzzi F , Giardini O , Quintieri F Barbato M, D'Eufemia P , Cardi E
Department of Paediatrics, University of Rome La Sapienza, Italy.
Panminerva Med 1995 Sep;37(3):137-41
Article Number: UI97023009
Abstract:
The etiopathogenesis of infantile autism is still unknown. Recently some authors have suggested that food peptides might be able to determine toxic effects at the level of the central nervous system by interacting with neurotransmitters. In fact a worsening of neurological symptoms has been reported in autistic patients after the consumption of milk and wheat. The aim of the present study has been to verify the efficacy of a cow's milk free diet (or other foods which gave a positive result after a skin test) in 36 autistic patients. We also looked for immunological signs of food allergy in autistic patients on a free choice diet. We noticed a marked improvement in the behavioural symptoms of patients after a period of 8 weeks on an elimination diet and we found high levels of IgA antigen specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for casein. The levels of these antibodies were significantly higher than those of a control group which consisted of 20 healthy children. Our results lead us to hypothesize a relationship between food allergy and infantile autism as has already been suggested for other disturbances of the central nervous system.
6) Immunizations with live viruses seem to make many of our kids worse. Wakefield, Singh, Fudenberg and others. This is a hotly debated issue. It will be working through the medical literature and government preventive health folks for a long time to come. Clearly, more research on vaccine safety must be funded by the governments that mandate vaccines.
7) Yeast species like candida are known to induce immune changes, as well as produce neurotoxins, and most autistic children have yeast problems on sensitive testing. Yeast may also interfere with the production of serotonin, an important neurotransmitter that controls behavior - in part (Moniliasis, 'autoimmune' polyendocrinopathy, and immunologic family study Wuepper KD, Fudenberg HH Clinical Experimental Immunology 1967 Jan;2(1):71-82) The Wuepper-Fudenberg Syndrome. Yeast also produce serotonin and may interfere with normal neuroregulation. (Candida Albicans As a Producer of Serotonin. Sokoloff,etal., Growth, 1967;31,297-300.) So normal brain chemistry in the presence of yeast is unlikely. Clostridia (a harmful bacteria) – found in approximately 20% of our patients, also cause neurotoxic effects.
8) These immunological changes (altered interleukins, cytokines, histamine, neurohormones, and other immune factors) effect brain chemistry, especially in the cerebellar and sensory components of the brain, and most autistic children have altered sensory perception.
9) Researchers at Johnson & Johnson have found a very toxic compound in the urine of children with autism - dermorphin. Dermorphin is only found one other place in nature - the poison of the Amazonian Poison Dart Frog! It is 10 million times more potent and toxic than morphine (Alan Friedman, PhD at J&J). Other researchers have confirmed it is always present in children with autism that receive even tiny amounts of casein or gluten.
10) In conversations with Dr. Horvath at the University of Maryland, I have been informed that children with autism are generally deficient of native secretin. Skoglosa etal from Sweden have found PACAP, a secretin family neuropeptide, is necessary for hippocampus development. The hippocampus processes immediate acquisition of data into new skills and is important in language development. (Molecular Brain Research 1999 Feb.19;65(1):1-13.) So it may be that secretin is also part of this system of hippocampal development. MRI data does not, however, support any evidence of significant size difference in the hippocampus between autistics and controls, so it may be a subtle effect, yet enough to be symptomatic.
**** Don't Panic, Faint or Otherwise get Overwhelmed. With God all things are Possible. We will be helping you. *****
What caused the immune injury or alterations? A genetic weakness (C4B null allele) and/or predisposition, combined with one or more of the following:
1) Shortened or absent breast feeding, preventing the full development of transferred cellular immunity. (Fudenberg)
2) Early gluten (usually wheat) introduction prior to one year of age. Wheat has been genetically manipulated in the last 100 years to increase the gluten content.
3) Early use of cow's milk or casein based formulas. (Allergenic and altered)
4) Immunizations with live viruses. Especially MMR after 1990. There is frequent regression after the MMR vaccine observed and published (Wakefield). Other vaccinations and resulting effects on interleukin or autoimmunity. (Singh)
5) Use of antibiotics and resulting yeast and pathogenic bacteria infection or overgrowth. (Shaw, Fudenberg, Wuepper)
6) Maternal allergy, chronic fatigue syndrome, or leaky gut problems that caused the child to be pre-sensitized in the womb. (Fudenberg)
7) Leaky gut from any number of the above or also related to parasites or GI infections in the child which allow gluten and casein to leak into the bloodstream. Once in they are altered by the body to toxic substances. Sucrose (table sugar) also leaks in and it is an abnormal sugar in the blood stream which causes a host of problems.
8) Defect in the detoxification pathway of the brain; Phenol Sulfur-Transferase or PST enzyme defect. Inadequate intake of sulphur compounds.
9) They develop autoantibodies to Myelin Basic Protein (Singh, Fudenberg, Gupta) and other brain components. Measles is known to induce MBP antibodies. I'll talk about this a lot more later.
10) Defective cellular immunity especially in the NK cell activity towards self and pathogens. (Fudenbereg, Gupta). And the possible elevation of Interleukin-2; see below:
Tolerance and ways to break it.
Author:
Nossal GJ
Walter and Eliza Hall Institute of Medical Research, Royal
Melbourne Hospital, Victoria, Australia.
Ann N Y Acad Sci 1993 Aug 12;690():34-41
Article Number: UI93378331
Abstract:
The overall picture as regards cellular mechanisms in immunologic tolerance is thus clear. Thymic negative selection is an important and dominant mechanism for both CD4+ and CD8+ T cells for those antigens (and they may be very many indeed), the peptides of which get expressed within the thymus. The induction of anergy among peripheral T lymphocytes may represent an ancillary mechanism in some cases, but this is not as clear as it appeared 2 or 3 years ago. Evidently, in many cases, T cells simply ignore antigens present only within specialized organs, and these T cells, even if only of low affinity for the antigen in question, could be provoked into auto immunity if sufficient help is provided, for example, through localized production of IL-2 or through provision of cross-reactive help. (Recall as mentioned above that IL-2 hypersecretion is associated with schizophrenia and I postulate we will find increased IL-2 in autism when we look for it.)
Part 2. What do I recommend be done to adequately diagnose which one(s) of these are problematic for your child?
Starting our appointment with as much biochemical and immunological information as possible means the meeting will be more productive and more efficient for both of us. Having evaluated hundreds of children with autism, we see fairly clear patterns in many cases. More information also means we can both come to better conclusions about the right course of treatment. If you do not have a cooperating local doctor you will need to contact our office to arrange for these tests prior to consultation.
We are happy to arrange telephone consultations with your local physician. We can do this before and/or after testing is accomplished. Our fees for this are available on request. We can also make available a vast amount of research material for you and your doctor.
To help you and your doctor understand where we are coming from get Biological Treatments for Autism and PDD by Dr. Shaw (we keep it in stock). Get the Conference tapes from the Biological Treatments Conference Shaw -Orlando 99 (we keep them in stock). These serve as foundations for your understanding of the immunological disorder we call autism.
**** Don't Panic, Faint or Otherwise get Overwhelmed. With God all things are Possible. We will be helping you. It's all important or I wouldn't waste either of our time with it. *****
Optimal Pre-Eval laboratory and dietary/nutritional interventions before seeing me or any doctor serious about biological treatment of autism.
Please Note: I can spend our consultation time telling you what test your child needs (which may be important) or telling you what appears to be wrong with your child (that seems like a better option to me). Ideally, I would like to have every test done before ever seeing your child. I also know that isn't always possible for any number of reasons. But if you are able to do all 14 items listed below, I should be more effective in biological intervention for your child.
For simplicity and quality assurance so we are comparing apples to apples, we try to limit studies to just 3 labs. They are:
Great Plains Lab, phone # 913-341-8949 (Bill Shaw, PhD, Director),
Great Smokies, phone #800-522-4762 (Martin Lee. PhD, Director), and
Specialty Labs, Santa Monica, California: phone # 800-421-7110.
1) If you look at the available medical literature, there are at least three highly reputable sources for the benefits of removing certain dietary items (gluten and casein) from the diet of children with autism. In the studies of Cade, Reichelt and Shattock, approximately 80% of autistics are significantly improved (not synonymous with cured) by the STRICT removal of gluten and casein. So I recommend a 100% gluten and casein free diet. Sorry, but 99% free doesn't count. We do this ourselves so I know what this means to your lifestyle. This means no: milk products, wheat, barley, oats, spelt or rye flours. (It is tough to do because most autistic children are fully addicted to the stuff - but there is enough emperic data and clinical observation to justify the one year trial). Dr. Paul Shattock at the University of Sunderland in the UK has tracked the urine of children with autism and found it takes up to one year to remove all the caseomorphine and glaidomorphine. Get Lisa Lewis PhD book Special Diets for Special Kids to help you get started on the diet and check out Dr. Bradstreet's wife's information on the website www.AutismNDI@aol.com (Lisa's book available from our office). So if you see even tiny results in the first 12 weeks be encouraged and keep it up. They may lose a few pounds during the switch to rice and potatoes, but they won't starve. Eventually they will start eating something else. Observe behavior during the wash out. Be aware that many family members and well-intentioned friends or teachers have the idea that "just a little won't hurt". This is wrong and there is good data to support why this is true, but if you really want to know if this is what is making your child autistic, then you must really police this. If you want the documentation on urinary peptides in your child, you could follow the instructions on page 144 of Shaw's book and send the urine to Reichelt at the National Hospital of Norway in Oslo. (It's easier than it sounds to get it there and you'll get good results). Soon, Ortho Clinical Labs will have an ELISA test available in this country. DR. CADE IS NO LONGER TESTING URINE - THE STUDY IS COMPLETE. Digestive enzymes: Warning- do not give enzymes to children who are eating gluten and casein. It may raise levels of opioids in the child. There is research ongoing to develop a peptidase enzyme that will lower opioids, but it is not commercially available yet (still in research). Parents always ask me how long they need to be gluten and casein free. My answer today, without a specific enzyme to digest these items (presently under research, but not available) - is until their children are ready to graduate from Harvard (forever).
2) Urine organic acid test performed by Great Plains Lab, phone # 913-341-8949. Requires a doctor's request.
3) Comprehensive Digestive Stool Analysis and Parasitology x 3 by Great Smokies Lab for parasites, digestive errors and yeast. Phone # 800-522-4762. Requires a doctor's request.
4) Draw Anti-MBP test #1056 and Anti-Neuron Filament Protein antibodies test #1052 at Specialty Labs 800-421-4449 in Santa Monica, California. (blood test). This is a must test. It may also be performed at Dr. Singh's lab at University of Michigan. Fax him a request with your telephone number or address to see his availability to perform the tests. His fax is 734-647-1829.
5) Get plasma serotonin levels checked with either Dr Singh at the University of Michigan or Quest Labs in California.
6) Genetic Screening: Plasma amino acid profile for evaluation of inborn errors of metabolism (our insurance lab is fine). Also get a fragile X and chromosome test to look for obvious errors. (Autism is not associated with obvious chromosomal defects even though it is likely a genetically predisposed problem). Autism may co-occur with Down's Syndrome, or any other genetic disorder since it appears to be an autoimmune problem independent of those other genetic issues. Below is a table of important genetic disorders that are not autism but may look a little like autism:
- Smith-Magenis – Chr 17p11.2 deletion – Hyperactivity, innatention, abnormal face appearance, head banging, excess hugging, sleep disturbances, pulling out fingernails, object insertion in mouth, anus, vagina, poor growth, and self injury.
- Prader-Willi – Chr 15p11.2 deletion – Hypotonia, excessive eating, food craving, stealing, hoarding of food, skin picking, obesity, obsessive –compulsive behavior, stubbornness.
- Williams – Chr 7q11.23 – Hyperacusis (sound sensitive) poor balance, socially disinhibited, heightened social ability, anxiety, compulsions.
- Rett's – Chr X-linked (girls only) Dementia, loss of language, small head, hand wringing, lip smacking, hyperventilation, sleep disturbances. (Special note: amazingly in the one 21 year old girl we have tried secretin on – marked improvement in social function and cognitive awareness were observed. I have not published this data yet, because we are waiting on further testing, but I would like to encourage others to research this area.).
- Neurofibromatosis – Chr 17q11.2 – Verbal and social disinhibition, inattention, and social awkwardness.
Fragile X – This is a somewhat more common disorder. Second only to Down's Syndrome in occurrence. The incidence is estimated from 1 in 2000 to 1 in 4000 children. The carrier rate for women is high, at approximately 1 in 260. But despite testing hundreds of kids, we have yet to see our first fragile X syndrome. It mimics autism in many ways, except the children have a distinctive appearance and subtle differences from autism. Boys are more commonly affected than girls. They have hypotonia, short attention span and hyperactivity. They also have language delay, impulse control issues, hand flapping, hand biting, and poor eye contact. You can see why this looks so much like numerous children with autism. Distinct from autism however, is their desire for relationships despite shyness. Fragile X results from methylation of the FMR-1 gene which prevents the FMR-1 protein (FMRP) from being made. FMRP is found in most cells but its highest concentration is in the brain. This deficit results in a brain that is too large, especially in the areas of the hippocampus, thalamus and caudate. The disorder has a broad range of phenotypic expression (what symptoms are visible) from profound mental retardation to normal IQ. (We would love to evaluate these children for a variety of issues – especially to see if secretin impacts their symptoms. If you have a child with documented fragile X please contact us for possible inclusion in our research).
Other Ill-Defined Genetic Issues: We also see a variety of apparently genetically abnormal children where chromosome abnormalities cannot be identified.
7) It's best to clear yeast, pathogenic bacteria and parasites and reconfirm that they are gone by re-testing, before our first visit if this is possible. Your doctor may be willing to help you with this. Many parents are finding resistance to this from their local doctors so we may need to wait on this until you arrive for consultation. Most importantly, reconfirm that the infestations are cleared. Medications I use are listed below in that section.
8) If you do not have good local medical support, and if your child has had any antibiotics, start reconstituting normal bacteria (Lactobacillus and Bifobacterium). Do this AFTER the stool and urine samples are sent off to the labs. 10 to 60 billion bacteria per day in a milk free base. It must specify that it is dairy free. Or use one Culturelle cap per day or (4) Primal Defense caps per day. We carry these.
9) Have a sleep EEG performed which is adequate to rule out Landau Kleffner Syndrome (these seizures are generally not apparent unless tested with EEG). LKS is defined as acquired aphasia with multifocal spike and wave seizure activity on EEG. Sometimes the seizures only occur during sleep. The reference below is presented to help your doctor understand our rationale:
Autistic regression and disintegrative disorder: how important the role of epilepsy?
Author:
Rapin I Saul R. Korey Department of Neurology, Department of Pediatrics, Albert Einstein
College of Medicine, Bronx, NY, USA.
Semin Pediatr Neurol 1995 Dec;2(4):278-85
Article Number: UI98084280
Abstract:
At least a third of autistic toddlers regress in language, sociability, play, and often cognition. Many fewer children undergo a similar, unexplained regression after language is fully developed (disintegrative disorder [DD]). Epilepsy or a paroxysmal electroencephalogram (EEG) with/without clinical seizures, including electrical status epilepticus in slow wave sleep (ESES), may be associated, in occasional children, with either selective loss of language (Landau-Kleffner syndrome [LKS]) or with pervasive autistic regression. Fluctuation in language and behavior deficits should raise the suspicion of epilepsy. Review of the literature and of the author's experience suggests that epilepsy probably plays a relatively minor, although non-negligible, pathogenic role in autistic regression. Multidisciplinary, possibly multi-institutional, longitudinal studies that encompass the regression are needed to sharpen diagnostic criteria to devise more effective therapies.
A QEEG (5 minute computer enhanced EEG) may be substituted as a screening test and if it is normal LKS is very unlikely.
10) Comprehensive allergy profile for foods and inhalants from either Great Smokies or Great Plains Lab for foods and inhalants (Blood test). Allergies likely play an important role in your child's behavior, but are not the cause of autism.
11) Get IgG with all 4 subclasses from either Great Plains or Quest. Get IgA with 2 subclasses, IgM, IgE, CBC, CD Lymphocyte subsets and NK cell activity tested (Quest or Specialty Labs). Check Blood Type (A,B,O,AB).
12) TSH, T3, T4 (blood test). Any lab will do.
13) Toxic Metal Screen from Great Smokies. (blood test)
14) Fasting Red Cell Fatty Acid test from Great Smokies or Body Bio (Dr. Pat Kane's Lab). (blood test)
End of pre-visiting testing and treatment - Start of other important issues.
1) Phytonutrients: a broad based plant source diet and/or supplements of plant concentrates are required for long term neuroprotection. They may be benefical for autism especially since almost nothing green gets past these kids' lips. . UltraGreen designed by me to help constipated autistics also provides vital phytonutrients to help the gut heal. We keep it in stock.
2) Avoid all excitotoxins: MSG, glutamate, glutamine, caseinates, hydrolyzed vegetable protein, natural flavorings, texturized vegetable protein, Nutrasweet*, aspartame, soups (unless it is specified that it contains no MSG). Also be very cautious with all prepared or restaurant food. Assume the worst. Go for plain food, e.g.: grilled fish or chicken, plain rice, steamed vegetables at restaurants.
3) Avoid sucrose (table sugar). Substitute with fructose. These children may have leaky guts so sucrose, which is a disaccharide, gets into the blood where no disaccharide belongs and wrecks havoc on your child's immunity.
4) In his book Eat Right For Your Type, Dr. Peter D'Adamo presents a very interesting argument for the immunological benefits of 'avoid' foods that express lectins (surface coding) that are like conflicting blood groups. If your blood type is A, the hospital and doctor know not to give you type B blood because it can kill you. Foods from different animals and plants also have lectin markers on their surfaces that look like blood group lectins. Since many children with autism also have leaky guts, food lectins can be exposed to your immune system, in a fashion similar to transfusion reactions and tissue rejection problems. This places an extra burden on the immune system. Interestingly, almost all autistics in our study are either A or O. Both of these blood groups cross react with gluten and casein products. We are still trying to learn what effect (if any) blood groupings have in autism.
5) Concurrent Therapies: Once the basic detoxification of yeast, gluten, casein, PST, etc., is accomplished and preferably after allergy treatment and secretin are going- start an earnest therapy program of Auditory Integration Therapy (AIT), Sensory Integration, Vision Therapy, Speech - Language, Occupational, and Behavioral Modification evaluations and treatments. The who does it and how of this are available in other references that we can direct you to. Do every therapy you can afford and fit into the time budget. More is generally better in the therapy world.
This constitutes the basic starting program. Medications and more sophisticated approaches require a skilled provider.
Secretin (a normal GI hormone) is in experimental use for autism and it is an intravenous injection of a normal occurring digestive hormone that tells the pancreas to release bicarbonate to stop stomach acid. It appears a significant number of autistic children have a defect here and in approximately 70% of children (Dr. Sid Baker's and Dr. Rimland's data which compares to our own) IV secretin has greatly reversed autism symptoms. The mean improvement is a 35% reduction in the autism rating scores after one injection. My own son responded like Parker Beck, the first child to show radical improvement. Victoria Beck, his mother, discovered the relationship and convinced doctors at the University of Maryland that secretin was helping her child's autism. See below:
Improved social and language skills after secretin administration in patients with autistic spectrum
disorders.
Authors:
Horvath K , Stefanatos G , Sokolski KN , Wachtel R , Nabors L, Tildon JT
Department of Pediatrics, University of Maryland School of Medicine, Maryland, USA.
J Assoc Acad Minor Phys 1998;9(1):9-15
Article Number: UI98246761
Abstract
: We report three children with autistic spectrum disorders who underwent upper gastrointestinal endoscopy and intravenous administration of secretin to stimulate pancreaticobiliary secretion. All three had an increased pancreaticobiliary secretory response when compared with nonautistic patients (7.5 to 10 mL/min versus 1 to 2 mL/min). Within 5 weeks of the secretin infusion, a significant amelioration of the children's gastrointestinal symptoms was observed, as was a dramatic improvement in their behavior, manifested by improved eye contact, alertness, and expansion of expressive language. These clinical observations suggest an association between gastrointestinal and brain function in patients with autistic behavior.
A copy of her research and experience is available from the ARI for $15 (all proceeds go to fund secretin research). This requires special knowledge and medical personnel to administer, but it is very safe. Currently, physicians that are using secretin (only a handful at this time) feel it must be repeated at intervals of 4 to 6 weeks. Results occur within the first 2 weeks in more than 50% of cases. It takes only a few minutes, but many children need sedation first. Immunization to secretin or other components with possible allergic reaction to secretin is a real possibility from longer term treatment. Secretin is approved as a diagnostic agent. Its use to treat autism is experimental. No assurance of response related to secretin can be made, but it is hoped that the data collected from the procedure will point our therapy in a more specific direction.
We don't exactly know how secretin works in autism. It does increase bicarbonate output so it changes GI function and organisms. It also acts in the immune system and brain via the PAPAC, VPAC and similar G receptors. It increases Cyclic AMP and stimulates cell function in certain cells. It may increase serotonin levels. It may help heal the small intestine. We are getting closer to understanding its function as these two abstracts indicate:
Distribution of pituitary adenylate cyclase activating polypeptide mRNA in the developing rat brain.
Authors:
Skoglosa Y , Takei N , Lindholm D
Department of Developmental Neuroscience, Box 587 Biomedical Centre, S-75123, Uppsala, Sweden.
Brain Res Mol Brain Res 1999 Feb 19;65(1):1-13
Article Number: UI99157067
Abstract: PACAP is a member of the secretin/vasoactive intestinal peptide (VIP) family, isolated from hypothalamus. Recent studies have shown that PACAP is expressed in many parts of adult brain. We have studied the precise distribution of PACAP mRNA in developing rat brain, employing in situ hybridization. PACAP mRNA is expressed in distinct parts of the embryonic rat brain from embryonic day 13, with a robust expression in developing cortex, hippo campus, amygdala and hypothalamus as well as in spinal cord and dorsal root ganglia. The expression in hippo campus and cortex diminishes towards adulthood, compared to new-born rat brain. In the mature brain, PACAP mRNA is located in alternating layers of cerebral cortex (layers I, III and V), in the dentate gyrus, in CA4 and CA1 regions, but not in CA2 or CA3 of the hippocampus. The presence of PACAP mRNA in different structures of developing rat brain suggests an important function for this peptide during brain development.
Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine,
endocrine, and nervous systems.
Author:
Arimura A
Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Jpn J Physiol 1998 Oct;48(5):301-31
Article Number: UI99069597
Abstract :
PACAP is a pleiotropic neuropeptide that belongs to the secretin/glucagon/VIP family. PACAP functions as a hypothalamic hormone, neurotransmitter, neuromodulator, vasodilator, and neurotrophic factor. Its structure has been remarkably conserved during evolution. The PACAP receptor is G protein-coupled with seven transmembrane domains and also belongs to the VIP receptor family. PACAP, but not VIP, binds to PAC1-R, whereas PACAP and VIP bind to VPAC1-R and VPAC2-R with a similar affinity. Despite the sizable homology of the structures of PACAP and VIP and their receptors, the distribution of these peptides and receptors is quite different. At least eight subtypes of PACAP specific, or PAC1-R, result from alternate splicing. Each subtype is coupled with specific signaling pathways, and its expression is tissue or cell specific. Although PACAP fulfills most requirements for a physiological hypothalamic hypophysiotropic hormone, it does not consistently stimulate secretion of the adenohypophysial hormones, except for stimulation of IL-6 release from the FS cells of the pituitary. The major regulatory role of PACAP in pituitary cells appears to be the regulation of gene expression of pituitary hormones and/or regulatory proteins that control growth and differentiation of the pituitary glandular cells. These effects appear to be exhibited directly and indirectly through a paracrine or autocrine action. Although PACAP stimulates the release of AVP, the physiological role of neurohypophysial PACAP remains unknown. One important action of PACAP in the endocrine system is its role as a potent secretagogue for adrenaline from the adrenal medulla through activation of TH. PACAP also stimulates the release of insulin and increases [Ca2+]i from pancreatic beta-cells at an extremely small concentration. The stage-specific expression of PACAP in testicular germ cells during spermatogenesis suggests its regulatory role in the maturation of germ cells. In the ovary, PACAP is transiently expressed in the granulosa cells of the preovulatory follicles and appears to be involved in the LH-induced cellular events in the ovary, including prevention of follicular apoptosis. In the central nervous system, PACAP acts as a neurotransmitter or neuromodulator, which has been supported by IHC and electrophysiological methods. More important, PACAP is a neurotrophic factor that may play an important role during the development of the brain. In the adult brain, PACAP appears to function as a neuroprotective factor that attenuates the neuronal damage resulting from various insults.
We know secretin binds to the PACAP receptor when given in the doses currently being used IV. This means Secretin likely emulates PAPAC function as a neurotrophic/neuroprotective hormone.
Transdermal Secretin: Once again Bernie Rimland and Victoria Beck have led the way. While originally I was very skeptical about transdermal secretin's ability to have the same dramatic effects as the IV version - with Victoria's urging I have found an easy way to keep it stable, effective and easily delivered by parents. Transdermal secretin with our current delivery system seems to enter the blood stream very quickly. Parents and children can taste the solvent within seconds of its application to the wrists. The doses are variable and require frequent adjustments. I have been using between 50 to 400 Gaspretin units per month in divided doses. It stays stable at freezer temperatures without freezing. We use N-DMS (far less irritating than DMSO and without the stink factor) to dissolve and extract the secretin with a special emulsified base.
Secretin Forms: Ferring had been the market leader until they decided to stop manufacturing it. Currently all the legal forms of secretin come from Switzerland. Human synthetic secretin is legal for use only on FDA approved research protocols. Purified porcine secretin via Switzerland to Japan in the form of Gaspretin is available in this country. Some of it is permitted use and some of it is brought in without permit. Gaspretin is measured with Japanese units which compare at about 1/6th the value of Ferring. So, a 50 unit Gaspretin ampoule equals about 12.5 CU Ferring. Our experience is that many children respond to this dose (50 Gaspretin units) when given IV. As with any medication, we want to us the least amount that gets the job done. We are happy to announce our research permit has been approved. US Research Permit for Gaspretin #46355 expires 07/19/2000. While we have a gaspretin/secretin permit, I am not aware of any other form of secretin permitted for import.
Please be careful!
Weak Immune Systems: Autism has been shown to have numerous associated immune defects. I have included a few abstracts to help you understand this:
Immunogenetic studies in autism and related disorders.
Authors:
Warren RP , Singh VK , Averett RE , Odell JD , Maciulis A , Burger RA , Daniels WW , Warren WL
Utah State University, Logan 84322, USA.
Mol Chem Neuropathol 1996 May-Aug;28(1-3):77-81
Article Number: UI97025765
Abstract: The major histocompatibility complex comprises a number of genes that control the function and regulation of the immune system. One of these genes, the C4B gene, encodes a product that is involved in eliminating pathogens such as viruses and bacteria from the body. We previously reported that a deficient form of the C4B gene, termed the C4B null allele (no C4B protein produced) had an increased frequently in autism. In this study we attempted to confirm the increased incidence of the C4B null allele in autism and investigated the presence of a C4B null allele in two other childhood disorders, attention-deficit hyperactivity disorder and dyslexia (reading disability). In addition, we explored the relationship of autism to the DR beta 1 gene, a gene located close to the C4B in autism. We confirmed the finding of an increased frequency of the C4B null allele in autism and found that the related disorders also had an increased frequency of this null allele. In addition, two alleles of the DR beta 1 gene also had significantly increased representation in the autistic subjects.
Plasma increase of interleukin-12 and interferon-gamma. Pathological significance in autism.
Author:
Singh VK
Department of Psychiatry, University of Michigan, School of Medicine, Ann Arbor
48109-0656, USA.
J Neuroimmunol 1996 May;66(1-2):143-5
Article Number: UI96265367
Abstract:
Immune factors such as autoimmunity have been implicated in the genesis of autism, a neurodevelopmental disorder. Since autoimmune response involves immune activation, the plasma levels of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), interleukin-12 (IL-12), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured in autistic patients and age-matched normal controls.
The levels of IL-12 and IFN-gamma were significantly (P < or = 0.05) higher in patients as compared to controls. However, IFN-alpha, IL-6, TNF-alpha, and sICAM-1 levels did not significantly differ between the two groups. Because macrophage-derived IL-12 is known to selectively induce IFN-gamma in T helper type-1 (Th-1) cells, it is suggested that IL-12 and IFN-gamma increases may indicate antigenic stimulation of Th-1 cells pathogenetically linked to autoimmunity in autism.
Elevated serotonin levels in autism: association with the major histocompatibility complex.
Authors:
Warren RP , Singh VK
Center for Persons with Disabilities, Utah State University, Logan 84322, USA.
Neuropsychobiology 1996;34(2):72-5
Article Number: UI97060689
Abstract
: Two of the most consistently observed biological findings in autism are increased serotonin levels in the blood and immunological abnormalities (including autoreactivity with tissues of the central nervous system). The purpose of this investigation was to determine if any relationship exists between these two sets of observations. Our laboratory has found and confirmed associations of the major histocompatibility complex (MHC) with autism. Since the MHC is known to regulate the immune system and is also associated with autoimmune disorders, we studied serum serotonin levels in 20 autistic subjects with or without MHC types previously found to be associated with autism. A positive relationship was observed between
elevated serotonin levels and the MHC types previously associated with autism.
Opioid-immune interactions in autism: behavioral and immunological assessment during a double-blind treatment with naltrexone.
Authors:
Scifo R , Cioni M , Nicolosi A , Batticane N , Tirolo C , Testa N , Quattropani MC ,Morale MC , Gallo F , Marchetti B Servizio di Psichiatria, Istituto OASI per lo Studio del Ritardo Mentale e l'Involuzione Cerebrale, Troina (Enna), Italy.
Ann Ist Super Sanita 1996;32(3):351-9
Article Number: UI97179824
Abstract:
The emerging concept of opioid peptides as a new class of chemical messengers of the neuroimmune axis and the presence of a number of immunological abnormalities in infantile autism prompted us to correlate biological (hormonal and immunological) determinations and behavioral performances during treatment with the potent opiate antagonist, naltrexone (NAL). Twelve autistic patients ranging from 7 to 15 years, diagnosed according to DSM-III-R, entered a double-blind crossover study with NAL at the doses of 0.5, 1.0 and 1.5 mg/kg every 48 hours. The behavioral evaluation was conducted using the specific BSE and CARS rating scales NAL treatment produced a significant reduction of the autistic symptomatology in seven ("responders") out of 12 children. The behavioral improvement was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase of the T-helper-inducers (CD4+CD8-) and a significant reduction of the T-cytotoxic-suppressor (CD4-CD8+) resulting in a normalization of the CD4/CD8 ratio. Changes in natural killer cells and activity were inversely related to plasma beta-endorphin levels. It is suggested that the mechanisms underlying opioid-immune interactions are altered in this population of autistic children and that an immunological screening may have prognostic value for the pharmacological therapy with opiate antagonists.
Boosting the function of Lymphocytes: this is still the cutting edge, but there appears to be some natural ways to do this. Mitake Mushrooms, Fresh Aloe (cheap and grows like a weed), and certain really vine ripened fruits (pineapples as example, but not necessarily their juice) seem to be active in inducing beneficial changes in cellular immune responses. Infectious illnesses are not required as evidence for T-cell dysfunction – autism itself, may be the symptom of T-cell dysregulation. If you want to use fresh aloe, start with the gel or pulp of about 1-2 inches of young growth. Squeeze this into a cup, mash and mix with fructose and dilute with white grape or pear juice (preferable organic). If diarrhea occurs or if already present and worsens, use less aloe and slowly try to increase the dose. If you want to spend a lot more money, aloe extracts are available in the health food store and from a multilevel marketing company (Mannatech). Results will vary. IP-6 (inositol hexaphosphate) is available from us. It is proven and patented as a supplement to increase Natural Killer Cell activity in cancer patients. We are researching its function in autism and believe it may be effective. It is absolutely safe. We have reason to believe it may be helpful in autism. Glucosamine sulfate is also an essential sugar that is readily available in stable form from us or at health food stores. Glucosamine seems to play an important role in wound healing, cartilage development and probably the immune system.
Allergy Treatment: Evaluate allergy status of the child: screening testing (done well by Great Smokies) for foods commonly consumed along with dust mites, cockroach, pollens and mold are potential starting points. If your child has confirmed allergic problems, I recommend you consult with either: pediatric allergist, Dr. Richard Layton in Baltimore, phone #888-337-2707 for intradermal testing and provocation neutralization or PN (which blocks the allergies), or Dr. Mary Ann Block of Dallas/Ft Worth, Texas area also does PN on autistic children #1-888-DR BLOCK. Both Dr. Layton and Dr. Block can manage all aspects of your child's evaluation and care, and are knowledgeable about secretin. Neither do IVIG. Other parents are reporting results from EPD (enzyme potentiated desensitization). I find the controls on this too cumbersome for management in autism.
Detox: Phenol sulfotransferase is an enzyme known to be deficient or inhibited in many autistics (Dr. Rosemary Waring, University of Birmingham, England). It is responsible for cleaning old neurotransmitters out of the brain and works within the liver to help remove other toxins. If the child has an unusual odor at night or on their bed clothes, or if they sweat while asleep (PST defect), use MSM 1500 to 3000 mgs per day. In one study from England, 83% of autistic children were PST abnormal and MSM should help this. It did in our son's situation. Natrol brand is OK and is at most drug stores. Since many of us find B6 or pyridoxine-5-phosphate helpful in autism, this following abstract brings the importance of MSM to children also supplemented with P-5-P or B6:
Inhibition of phenol sulfotransferase by pyridoxal phosphate.
Authors:
Bartzatt R , Beckmann JD
Department of Internal Medicine, University of Nebraska Medical Center, Omaha
68198-5300.
Biochem Pharmacol 1994 Jun 1;47(11):2087-95
Article Number: UI94280442
Abstract:
The biologically abundant cofactor, pyridoxal-5-phosphate (PLP), is a potent inhibitor of bovine phenol (aryl)
sulfotransferase (PST). Preincubation of purified enzyme with as little as 1 microM PLP decreased PST activity by 50%. Excess 2-naphthol protected PST from inactivation by PLP, whereas 2-naphthyl sulfate and PAPS were not protective. Although PLP inhibition was apparently competitive with 2-naphthol, a steady-state kinetic Ki value could not be measured due to non-linear Lineweaver-Burk plots in the presence of the inhibitor. Kinetic progress curves revealed that this was due to progressive loss of activity during catalysis. The kinetics of inactivation of PST by PLP were pseudo-first-order and exhibited saturation. The derived KI value for the binding of PLP to PST in the initial reversible step was 23 microM, with a maximal rate of inactivation of 0.077 min(-1). Absorbance spectra of the PST/PLP complex indicated the formation of a Schiff base conjugate, and this is consistent with decreased electrophoretic mobility of the protein-PLP adduct in the presence of dodecyl sulfate only after reduction with borohydride. These results point to the possible regulation of an important detoxification enzyme by a ubiquitous cofactor.
This is not an argument against B6 or P5P since I use both and have seen helpful results in some children, but obviously it is an interesting bit of data, since we don't know why P5P or B6 benefit autistic symptoms. |
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