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Extract from Nutrition Therapy by Stephen J. Gislason, MD
In 1994 I was diagnosed with celiac disease, which led me to create Celiac.com in 1995. I created this site for a single purpose: To help as many people as possible with celiac disease get diagnosed so they can begin to live happy, healthy gluten-free lives. Celiac.com was the first site on the Internet dedicated solely to celiac disease. In 1998 I foundedÂ The Gluten-Free Mall, Your Special Diet Superstore!, and I am the co-author of the book Cereal Killers, and founder and publisher of Journal of Gluten Sensitivity.View all articles by Scott Adams
Foods derived from cereal grains (wheat, rye, barley, oats) are popular staples in our diet. In the past decade especially, a renewed enthusiasm for "whole grains", and increased dietary fiber, has lead to increased consumption of these cereals in relatively unrefined form, and often in combination, as with granola cereals, and whole wheat breads fortified with bran, coarse flours, and other additives. The argument in favor of whole grains is based on two considerations:
1) The nutrient content of whole grains and their unrefined flours is greater than refined flours. White flour has been considered by some an inferior food since it is missing some micro-nutrients. However white flours and light white bread are sometimes better tolerated than the whole grain foods.
2) The indigestible fiber in whole grains contributes to stool bulk, reduces the opportunity for constipation, and absorbs toxic or harmful molecules, which, escorted from the bowel by fiber, have less opportunity to do harm. The regulating and binding actions of grain fibber, it is argued, would reduce the incidence of bowel cancer, if eaten over a lifetime. The favorable fibers are probably better found in vegetables and fruit. While there favorable arguments for a high cereal grain intake there are major problems with these foods. Craving and compulsive eating of flour-based foods is common, especially the reward an dessert foods, containing sugar. These high-carbohydrate foods contribute the major caloric input to obese persons.
The diseases clearly associated with Cereal grains or "Gluten intolerance" are the bowel disorders bearing the names,"celiac Disease", "Non-Tropical- Sprue", or "Gluten-Enteropathy", and the skin disorder, dermatitis herpetiformis.
The clinical presentations of cereal-grain intolerance, which can be recognized from the history or pattern of illness alone include: Diarrhea, chronic with malabsorption, weight loss, micro-nutrient deficiencies, blood loss and anemia. Abdominal pain may be recurrent and associated with flutulence, distention, and intermittent bowel motility disturbance. Minor gluten-enteropathy may not involve diarrhea, and malabsorption may be inconspicuous or inconsistent. A nutritional anemia may be the presenting problem, although the patient will have an associated history of intermittent abdominal pain and distension. The anemia results from malabsorption iron, folic acid and/or vitamin B12.
Arthritic or Fibrositic Syndromes: Aching, stiffness, and fatigue are three common symptoms which occur together in a variety of disorders, and occasionally remit completely on an elimination diet which excludes cereal-grains and other allergenic foods.
Brain Disturbances: symptoms include deep, burning sensations in arms and legs, restless legs, numbness and tingling which comes on rapidly with sitting, squatting, and lying in bed; brain effects are manifest by a sense of confusion or "fuzzy-head, disorganization, irritability, and memory impairment. The occurrence of resting pain in joints, particularly the hands with slight swelling, and stiffness is the early prevention of rheumatoid arthritis; it can occur strictly as a manifestation of wheat (and other food) allergy. The activity of rheumatoid arthritis may be reduced in some patients by cereal grain and other allergenic food restriction.
There are at least four mechanisms involved at the bowel level for gluten intolerance:
3) Increased permeability of the bowel to macromolecules including the antigenic protein and its fragments.
4) Increased production and release of mediators such as histamine, seratonin, kinins, prostaglandins, and interleukins.
A wheat gluten-triggered mechanism has been studied in rheumatoid arthritis patients. The clinical observation is that wheat ingestion is followed within hours by increased joint swelling and pain. Little and his colleagues studied the mechanism, as it developed sequentially, following gluten ingestion. Platelet Seratonin Release in Rheumatoid Arthritis: A study in Food Intolerant Patients. Little C. Stewart A.G., Fennesy M.R. Lancet 1983.297-9.
The Gluten Proteins
Gluten is a mixture of individual proteins, classified in two groups, the prolamines and the glutelins. The most troublesome component of Gluten is the Prolamine, Gliadin. It is Gliadin in wheat that causes the major problem in celiac disease, and Gliadin antibodies are most commonly found in the immune complexes, associated with major systemic disease (Unsworth, D.J., et. al., IgA Anti-Gliadin Antibodies in Celiac disease, Clin Exp Immunol. 1981: 46:286-93.Keiffer M, et. al., Wheat Gliadin Fractions and Other Cereal Antigens Reactive with Antibodies in the Sera of of Celiac Patients, Clin Exp Immunol. 1982;50:651-60).
We eat the seeds of the grain plants. The seed has a bran casing, a starchy endosperm which contains 90 % of the protein, and a small germ nucleus which is the plant embryo, waiting to grow. Any flour made from the starchy endosperm contains prolamines and is potentially toxic to the grain intolerant person.
If we look at the different grains we find that each has its own prolamine. The following list gives the type of prolamine each grain contains, and the percentage of protein the prolamine has in relationship to the entire grain:
- Wheat - Gliadin - 69%
- Rye - Secalinin - 30-50%
- Oats - Avenin - 16%
- Barley - Hordein - 46-52%
- Millet - Panicin - 40%
- Corn - Zien - 55%
- Rice - Orzenin- 5%
- Sorghum - Kafirin - 52%
Celiac disease may serve as a model of wheat allergy. No-one should make the mistake of assuming this is the only form of wheat allergy. When wheat is the principle problem food, there is a consensus that barley, oats, and rye must be excluded as well. Millet, is intermediate in the list of offenders; corn and rice are usually tolerated when gluten prolamines are the chief and only food intolerance, although corn is a major food-allergen in its own right. Triticale is a new hybrid grain with the properties of wheat and rye, and is excluded on a gluten-free diet [Bell L., Hoffer M., Recommendations for Foods of Questionable Acceptance for Patients with Celiac Disease, J.Can. Dietetic Ass'n: 1981; 42:2; 143-15]. The identity and the amount of the prolamine decides the kind of reaction that is likely to occur. It should be noted that there is considerable variability in the prolamine content of various foods made from cereal grains, and this variability is one of the many reasons why food reactions are not consistent.
The usual definition of celiac disease links chronic diarrhea, with evidence of malabsorption, and changes in the surface of the small bowel. Most medical textbooks dogmatically state that an intestinal biopsy must be taken and must show typical changes before the diagnosis is made. The biopsy allows a pathologist to examine microscopically the surface of the small intestine. The surface of the small intestine is covered by a dense mat of projecting nipples called villi which shed cells containing digestive enzymes, and absorb food molecules. In long-standing celiac disease one expects the villi to be blunted and the surface to be smoothed out. While the biopsy is a useful procedure it has several drawbacks;
It is a procedure with a small incidence of dangerous complication, especially bowel perforation.
It is a small sample and may miss patchy or irregular bowel changes.
Significant protein intolerance, and increased bowel porosity may exist despite normal appearance of the bowel lining under the microscope.
Patients in remission or with intermittent symptoms may have normal biopsy results but remain exquisitely sensitive to some prolamine, or peptide fragment challenges. [Bjarnson, I., et. al., Intestinal Permeability Defect in Celiac Disease, Lancet. 1983 1284-85].
The most significant test of gluten intolerance is remission of symptoms when grains are eliminated for a trial period of 3-6 weeks. I have often reviewed the history of patients with chronic diarrhea, and associated abnormalities, who have been "thoroughly investigated" in an academic center and left untreated because their biopsy result was normal. Physicians, who make therapeutic decisions solely on the basis of biopsy results are being dogmatic, not scientific, and certainly not serving the best interests of their patients who simply want to be better. Investigations which do not lead to effective therapy are of no value to patients.
Diagnosis of gluten-sensitivity in all disorders may be facilitated in the near future by better immunological laboratory tests, including measurement of circulating serum antibodies directed against these proteins, and of circulating immune complexes which contain food antigens. [O'Farrelly, et. al., Alpha-Gliadin Antibody Levels: A Serological Test for Celiac Disease, 1983 Lancet; 286:2007-2010]. Better tests would permit the demonstration of increased GITPERM, and the entrance of abnormal macromolecules after test meals. Eventually the path through the body of such molecules may be studied by labeling them with isotopes, and tracking them with scanning methods like positron emission tomography.
Irritable Bowel Syndrome
An unexplained bowel disturbance, characterized by abdominal pain, gas, diarrhea, often alternating with constipation, is diagnosed as the "Irritable Bowel Syndrome" and too often attributed to "psychogenic causes". We recognize right away that the label "psychogenic causes" describes the lack of biological understanding more than it describes the patient's problem. The treatment usually offered includes bulk laxatives, tranquilizers mixed with antispasmodic drugs, and not infrequently, a trip to the psychiatrist, who is not likely to do a dietary history. The success rate with these methods in one study was only 12%! [Waller, S.L., Misiewicsz: Lancet 1969 ii: 753-6, Prognosis in Irritable Bowel Syndrome].Food studies are seldom undertaken in the assessment of patients with irritable bowel syndrome. Not a single patient whom I have seen with this disorder has had a food diary examined, nor any trial of exclusion diets. Dietary advice commonly-given includes "high-fibber" diets, usually increased cereal grains, which are contraindicated. Studies which allege to rule out food intolerance are poorly conducted, often basing negative results on limited, selected food challenges. Proper studies would utilize the complete methodology of diet revision therapy, and would observe patients in real-life conditions, ingesting real food over a significant period of time.
The irritable bowel syndrome is at least in part a food-intolerance disorder, and the program outlined in this book will generally be helpful. In a recent study by V. Alum Jones et al, food intolerance was shown to be a major factor in causing the irritable bowel syndrome in 25 patients. This study is of particular interest because it was arranged to reveal something of the mechanism of this disorder. The results indicate that this particular presentation of food intolerance was not the result of immune events, was not associated with high blood-histamine levels, nor circulating immune complexes. Rather the disturbance seemed to be related to increased levels of Prostaglandin E2 (PGE2), synthesized and secreted by the bowel itself. Prostaglandin production is inhibited by ASA, and all of the other anti-arthritic medications, and may prevent the irritable bowel effect if taken before meals. The foods causing the irritable-bowel symptoms were (in order of frequency)
- Corn .... 5
- Milk.... 4
- Coffee. 4
- Tea..... 3
- Citrus.. 2
All the patients found to be intolerant of wheat had normal results of intestinal biopsy. Not all wheat-induced bowel disorders are celiac disease! The important point, once again, is that the mechanisms of food intolerance are multiple and complex! The only practical way to study food intolerance is by trials of dietary revision, and challenges with real food. One interesting observation made by several of my patients is that they always got somewhat better while in hospital, having multiple tests done. Psychological factors? No. Hospital tests for gastrointestinal disorders always involve days of fasting. If you stop eating foods that are hurting you, your symptoms improve! Proper NP may avoid the waste, in terms of dollars and disappointment, that inappropriate medical investigation and treatment incurs, when a trial of appropriate DRT will often cure the "disease" under investigation.
This not to deny that emotions influence bowel function, since this is clearly the case. The "Gut Brain Axis" has become a subject of specialized study because of the complexity of interaction of these two life-determining organ systems. Food selection, emotional experiences, and eating behaviors interact complexly. Anger, frustration, fear will profoundly influence food selection, appetite, digestion, and metabolism; while food selection, digestion and metabolism will determine your emotional reactivity. There is a continuous loop of causal relationships, not a one-way vector. When patients are told they have bowel dysfunction because of stress, tension, or anxiety, this is only a half truth. The other half of the truth is that patients have stress, tension, and anxiety because of bowel dysfunction.
The more subjective mood-related symptoms are difficult to assess, and are attributed to "psychiatric causes" although no authority seems to know what that means! The brain effects are an expression of disorderly molecular flow through the brain. Specific nuero-active effects of grains include the circulating peptides, which have been described earlier in the book, as WMOD, and are further discussed in the last section of this chapter.
Indications for Trial of Gluten Restriction
NP advocates liberal gluten restrictions in a variety of circumstances, simply because the results are surprisingly good. The core diet developed by clinical trials, and described in subsequent chapters is initially free of cereal grains, since they are frequent offenders in food intolerance problems. Not only patients with bowel disorders benefit, but also people whose bowels function apparently well but suffer, fatigue, aching, swelling, and brain disturbances, expressed as mental and emotional upheavals.
The specific patterns of disturbance which should invite a trial of the food-testing plan, and gluten restriction specifically are: Diarrhea, prolonged over three weeks, not associated with infections, or evidence of parasites or pathogenic bacteria in stool samples.
Abdominal pain, especially if frequently recurrent, and associated with excess gas, and abdominal distensio (Irritable Bowel Syndrome).
Anemia from iron, folic acid, or nutrient deficiency which is unexplained by blood loss, or dietary inadequacy, especially if associated with abdominal symptoms.
Aching disorder, especially if the aching is generalized, associated with stiffness with inactivity, and dysethesiae ( odd burning, tingling sensations), and tender muscles. Any arthritic pattern, associated with diarrhea should be vigorously managed with gluten, milk, and egg restriction with careful testing of other foods for possible reactions.
Fatigue, especially if associated with irritability, confusion or fuzzy-headedness, headache, and abdominal discomforts.
Chronic asthma and rhinitis.
Neurological symptoms which are unexplained by recognized abnormalities in physical examination and laboratory investigations. These symptoms include the above mentioned, memory disturbances, sleep disturbances, visual distortions, muscle weakness, and fasiculations (wiggly, jerking movements within muscles). A trial of gluten restriction is also appropriate in children with learning disability, schizophrenics, alcoholics, and patients with refractory mood disorders.
Treatment of Grain Intolerance
Exclusion of wheat, rye, barley, oats, and millet are the initial steps when gluten intolerance is suspected. The exclusion includes all the foods made with the flours of these common grains - Durham flour, Triticale, and Bugler are all excluded. The bran of these cereals is also excluded. A trial of an elimination diet lasting 3-6 weeks is sufficient to experience significant improvement in most bowel conditions. Longer periods of exclusion are required in conditions with chronic tissue inflammation, especially arthritis, and the skin disorders, eczema, and dermatitis herpetiformis, which sometimes requires an exclusion of several months before the skin condition remits completely.
It is important to realize that multiple food intolerance are common and should be assumed, rather than assuming that single food intolerance's are the problem. NP does not consider it adequate therapy for a single food group to be eliminated, on the assumption that every other food will be well tolerated. Gluten restriction should be part of a more comprehensive dietary study, preferably in the form outlined in the food-testing plan. The best dietary plans are based on what is good to eat, more than what is bad to eat! No-one wants to be confronted with long lists of foods they must avoid. It is better to build a diet from scratch, emphasizing the positive. There is an entire universe of foods not related to milk, gluten-cereals, and eggs, the commonest problem foods!
If improvement occurs, gluten restriction is maintained for many months at least before any effort is made to re-challenge with gluten foods. There are two exceptions, millet and oats. Millet is occasionally acceptable, early in an exclusion program although few people find it an attractive food, and it is potentially a trouble-maker.
Oats is probably the best cereal to be re-introduced, and is often tolerated when wheat, rye, millet and barley are not. If gluten restriction is beneficial, oats may be tried after 2-3 months of abstinence. Some people, however, have specific and dramatic allergic reactions to oats, and acceptability must not be assumed. The major substitute for cereal grains is Rice The rice prolamine, orzenin, is different enough from gliadin to avoid immunological cross-reaction.
Rice: Desirable Staple Food
Rice is the staple food chosen for the core diet because it has low allergenicity, is versatile, widely available, and provides a carbohydrate caloric base to the diet. Rice comes in many varieties some of which are sufficiently different to be treated almost as separate foods.
Converted white rice is preferred at the start of a core-diet program. Brown rice does contain more nutrients, and some prefer it by taste and texture; however, the husk also contains more potential problems. Rice-eating peoples generally polish their rice, removing the husk, because empirically the result is better. Again the nutritional arguments based on the nutrient content of foods outside of the body may be misleading! Brown rice may be well-tolerated, but should be introduced after tolerance for converted white rice is established. There are definite exceptions to this rule, as with all rules, since some patients do report better tolerance of selected varieties of brown rice.
Rice can be utilized in a variety of forms, including rice cereals, rice pablum, puffed rice, rice-cakes, rice noodles, rice vermicelli, and rice flour (starch). Different rices vary sufficiently in taste, and texture to maintain culinary interest. Rice may be boiled with sunflower seeds, buckwheat, wild rice, other seeds, and legumes for added nutritional and culinary variety.
All foods, including rice have the potential to be allergenic, however, and are not exempt from suspicion when adverse food reactions continue on a substitution diet. The most typical symptoms of rice intolerance are heavy fatigue, and chilliness. Rice may also produce the total grain syndrome, although this is uncommon in my experience. Following the core hypoallergenic diet plan, you will simply not miss cereal grains for a while, and find the variety and diversity of other vegetables, sufficient to sustain your interest and nutrition. The biggest challenge is to make the effort to choose different foods, and to prepare them attractively.
Corn is less well tolerated than rice< and is implicated in non-immunological bowel disorders. Corn should be introduced cautiously in the third or fourth week of a food re-introduction program, in limited amounts. Corn appears in a multitude of products including snack foods, oils, margarine, cereals, and it is easy to overdose on this food.
Our packaged, fast-food, and restaurant-food industries rely heavily on wheat flour to produce their products. The person on a gluten-free diet must make an extra effort to avoid these products, and to eat instead primary foods, including fresh produce, meats, fish, and rice.
Most of my patients crave a carbohydrate food, if not a sugar food, then bread, buns, crackers, chips, nuts and so-on. Rice is a good alternative, being a starchy vegetable which turns sweet if you chew it for a while. Having rice available in a bowl in the refrigerator, mixed with vegetables, herbs, meats or fish offers an alternative to gluten-laden snack foods. Pasta is made with high gluten flour and is off our list of core diet foods. Again Rice is good alternative to pastas.
Buckwheat is an interesting grain-like food to add to your diet, especially if Rice is not acceptable because of an adverse response to it. Buckwheat is not a grain, but belongs to the Polygonaceae family which includes sorrel, rhubarb and dock. Buckwheat is a seed, however, and resembles the grains in having a starchy endosperm, and can be ground into a flour, or cooked as a cereal, or prepared as rice. Buckwheat is not toxic to the celiac bowel, although some people react adversely to it. Buckwheat flour is disappointing for baking since it lacks gluten, the elastic, chewy component of bread.
Other Alternatives to Cereal Grains
Other starchy vegetables may stand in for grains. The potato is a starchy tuber, and potato starch can be used as a weak imitation of flour. Other roots are available, including Cassava an African vegetable which produces Arrowroot flour Tapioca is made by heating and moistening arrowroot. Flour is also made from Taro, a Japanese tuber, which is common in Hawaii where POI is a staple paste made from Taro roots. Soya beans are versatile and highly nutritious seeds which can be utilized as a flour as well. Tofu is the protein fraction of Soya beans, and is an inexpensive, nutritious food, used widely in the orient as a protein staple. It must be mixed with corn or another legume to produce a full complement of essential amino acids. The main problem with tofu is learning how to cook with it. Other legumes including, chick peas, lentils, peanuts are useful foods, on a gluten restricted diet, but have their own problems which must be considered before regular use of these foods is entertained.
Each recommended food is still subject to testing, however, for each food may produce allergens or cause other problems. As with all foods in a sensitive person, the basic rule is - Find out how the food works in your body! Gluten-free diets specify food exclusions, including a variety of manufactured foods which contain Gluten. One generally can figure out what is not desirable by thinking of the probable origins of the food in question. Gluten exclusion does include malt, a barley product, and malt containing beverages (Postum, Ovaltine); beer and ale. Alcohol is usually excluded, although some tolerance may be found to selected wines, and distilled beverages. [Food for Celiacs; Campbell, J.A. : Journal of the Canadian Dietetic Ass'n., Jan '82 ; 43:1; 20-24; Gluten Free Cookbook: Leicht, L., RR#1 Box 54, Pender Island B.C. VON 2MO; Club House Foods 316 Rectory St. PO Box 788 London Ont. N6A 4Z2].
The focus of a gluten-free cookery is often on replacing gluten flour in baked goods with starches made from rice, arrowroot, potato, Soya beans, other legumes like chickpeas,and wheat starch (all the protein has been carefully removed). While baking can be done with these non-gluten "flours", the results are never as satisfying as with wheat flour. Gluten is the most desirable ingredient in flour for producing bread, and baked goods, and its absence is conspicuous. In many respects it is easier, kinder, and nutritionally wiser to forgo the baked goods in large measure and eat other foods. The task of changing your diet is very much like moving to another country and culture. You may try to bring all your old habits with you, and struggle to get all of the ingredients that you are used to forming into meals, or you can gracefully, and with a sense of adventure try the new cuisine. Certainly bakery foods are delicious and tempting, but so are creatively prepared rice, vegetable, fruit, fish, and meat meals. Even with multiple exclusions, an appealing, varied diet is within reach if you are willing to change your eating style. A book of recipes which de-emphasizes, cereal-grains, eggs, and milk is a great asset. The cookbook "Oriental Food Feasts" is full of recipe ideas from China, Japan, Indonesia, and India. One has to select recipes that utilize foods, appropriate to your dietary needs. The main thing is to be inspired to create and enjoy a new cuisine that will diminish your disturbances, sustain your interest in food, and provide balanced nutrition. [Shepard, S.M., Oriental Food Feasts, Arco Publishing, Inc. New York 1979]. Vegetable selection and preparation is one of the prerequisites of a successful diet revision. The Tassajara cookbook is my favorite introduction to the subject [Tassajara Cooking; 1973 Zen Centre; San Francisco; Shambala Publications, Inc. Boulder, CO.] .
Neuropsychiatry & Gluten Intolerance
We have recognized that Gluten intolerance may involve the absorption of complete proteins like gliadin, or its peptide- fragments; anti-protein antibodies circulating in the blood, which form immune-complexes with the food protein, and provoke the release of mediators which may cause multiple disturbances in all body systems, and even tissue damage. These circulating problems may also influence brain function in a variety of undesirable ways. There is vague circumstantial evidence of an adverse grain effect on metal status. A family history of psychiatric problems is more common in patients with celiac disease. Celiac disease is genetically determined involving two or more concurrent genes. The genes involved are part of the immune-recognition complex, which determine the "Self" identity markers, protecting one's own cells from attack by the immune system. Celiac patients have an increased frequency of the serum histocomptability antigens (self-markers) of the HLA-B8 and HLA-Dw3 types. This genetic marker may indicate a predisposition for bowel absorption abnormalities or immunologic propensities, which result not only in celiac disease itself but other contingent abnormalities as well.
Schizophrenia has been associated with gluten intolerance. The diagnosis, schizophrenia, describes a variety of differing individuals who belong to complex group of brain-disordered people. The schizophrenic brain distorts sensing, feeling, remembering, deciding, and acting. It is unlikely that schizophrenia is a single disease with a single cause. The milder, but similar brain dysfunctions which I observe commonly with gluten and other food intolerance, suggests that food allergy may play a role in schizophrenia, with gluten as a frequent triggering antigen. Dr. F.C.Dohan has consistently advocated a gluten-schizophrenia link for 20 years [Dohan, F.C., Cereals and Schizophrenia: Data and Hypothesis, 1966 Acta Psychiatr. Scand 42:125-42; Dohan, F.C. More, Celiac Disease as a Model for Schizophrenia, 1983 Biol. Psychiatry 18:561-4].
Dr. Dohan states:
[" Many diseases are caused by genetically-deficient utilization of specific food substances. Perhaps the best studied example is phenyketonuria... far more common disorders, for example, atherosclerosis, and coronary heart disease, are strongly suspected of being due to genetically defective utilization of certain food constituents. " Similarly, considerable evidence indicates that the major cause of schizophrenia is the inborn inability to process certain digestion products of some food proteins, especially cereal grain glutens..."]
Among Dr. Dohan's interesting an relevant recommendations is the idea of a "Gluten tolerance test". Such a test has not yet been developed, but is the sort of evaluation method that NP advocates in general. A gluten tolerance test could be initiated with routine evaluations before and after ingestion of grain foods. More sophisticated versions would measure gluten proteins and derived peptides in the blood, and would track the path of these molecules into organs, especially the brain. Finally the impact of these molecules would be evaluated by monitoring the function of the target organ in real time. I have been eager to do real-time monitoring of brain activity, topologically-computed in gluten-sensitive patients. These patients report changes in their PSYE, cognitive abilities, and emotional state which no researcher to date has documented objectively. The problem of adverse brain effects of molecules derived from food is a major under-recognized phenomenon of nutrition and molecular pathophysiology. Research in the next 10-20 years will, I am convinced, reveal a great deal about the extent, mechanisms, and importance of this consequence of eating to our mental status.
from "Nutrition Therapy" by Stephen J. Gislason, MD
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