Surgery – Diagnostic testing
Reexamination Certificate
2000-11-15
2003-01-28
Winakur, Eric F. (Department: 3736)
Surgery
Diagnostic testing
C128S898000
Reexamination Certificate
active
06511425
ABSTRACT:
The present invention relates to a new method for the diagnosis and evaluation of adverse reactions to food, so called food intolerance, in particular coeliac disease.
BACKGROUND OF THE INVENTION
Food intolerance is an adverse reaction to a food or food component that does not involve the IgE-mediated immune response seen in classic food allergies, e.g. cow milk allergy. Food intolerance reactions can be triggered by a physical reaction to a food or food additive. For example, people with lactose intolerance do not have enough of the enzyme lactase, to digest the lactose naturally present in milk. This is one of the most common food intolerances and can be managed through diet and the use of enzyme preparations, such as Lactaid® caplets or drops. Another ailment is coeliac disease, where the patient reacts to the gluten in cereal foods.
Further, certain food additives such as flavour enhancers (mono sodium glutamate) or preservatives (sulphates) used on foods may cause a food intolerance reaction in some people. The symptoms of food intolerance vary and can be mistaken for those of a food allergy or other ailments.
Coeliac disease or malabsorption syndrome is a syndrome mainly affecting children, but also adults, caused by a reaction to gluten which prevents the small intestine from digesting fat. In adult coeliac disease, the adverse reaction to gluten is known to cause atrophy of the intestinal villi, so that the surface available for absorption becomes smaller. The symptoms of coeliac disease include a swollen abdomen, diarrhoea, abdominal pains and anemia.
It is known that intolerance to wheat gluten is a major factor in the aetiology of the enteropathy observed in almost all children with coeliac disease and most adults with idiopathic steatorrhoea. Diagnosis has frequently been based on dietary changes, namely putting the patients on a gluten-free diet and observing the possible recovery
ormalisation.
The gold standard for the diagnosis of coeliac disease remains a jejunal biopsy showing typical mucosal lesions of the small intestine including villous atrophy. Biopsies may be taken before and after exclusion of gluten in the patient's diet. Following the introduction of a gluten-free diet, the intestinal mucosa will regenerate and the symptoms normally disappear.
Controlled reintroduction of gluten or a rectal gluten challenge combined with colonoscopy or the examination of a biopsy sample has been experimentally used to confirm the diagnose.
It has been suggested that coeliac disease can be diagnosed using jejunal biopsy, taken with a Watson/Crosby capsule before and after an oral FF3 challenge. FF3 (Frazer's fraction III) is a peptic-tryptic digest of gluten that is known to damage the mucosa of the small intestine in gluten-sensitive subjects. The biopsy samples are prepared and the number of intraepithelial lymphocytes is estimated. A result can be available within 24-48 h which prompts the authors to call this a “rapid confirmatory test of gluten sensitivity in patients already taking a gluten-free diet” (Loft, D. E. et al., Lancet, 335 (1990) 1293-1295).
It is known that nitric oxide (NO) is produced at many sites in the gastrointestinal tract and believed to participate in both physiological and pathological events (Whittle G. J. R., Physiology of the Gastrointestinal Tract, New York: Raven Press (1994) 267-94).
It is further known through WO 96/17244 (by Kjell Alving, Edward Weitzberg, Jan Lundberg and Jon Lundberg) that inflammatory states in the intestines can be detected by measuring the concentration of nitric oxide in a gas sample, taken from the intestinal lumen. This method has hitherto been implemented in the diagnosis of Crohn's disease and ulcerative colitis.
Further, a method and device for the diagnosis of allergies has been disclosed in U.S. Pat. No. 5,983,899, which method comprises analysing a sample that has been taken rectally from the large intestine of a patient who is suspected of being allergic, after having provoked the mucous membrane of the patient's large intestine rectally with an allergen against which the suspected allergy of the patient is directed. The method is illustrated by examples, where nine patients suffering from coeliac disease were examined using a rectal perfusion technique using a six-channel PVC hose having an inner diameter of 10 mm, an outer diameter of 16 mm and a total length of 38 cm. Three inflatable balloons were fastened to the hose, to obtain a rectal perfusion segment of 8 cm in length. Two rectal perfusions were performed on each individual on one and the same day: a basal perfusion and a perfusion three hours after introducing gluten. The participants were studied after having fasted for 17 hours and 4 liters of an oral laxative solution was used as an enema. The disclosure of U.S. Pat. No. 5,983,899 also comprises an instrument for rectal insertion in the rectum, having an expandable part which surrounds a central channel which opens out on each side of the expandable part, and a separate channel through which expansion of the expandable part can be controlled such that when the instrument is applied in the rectum; the outer wall of the expandable part will be in direct contact with the mucous membrane of the rectum; and wherein a diffusible allergen and a receptor for an inflammation marker are present on an outer defining surface of the expandable part.
In summary, it remains a problem to make available a simple, rapid, safe and reliable test for determining the occurrence of food allergy and food intolerance, and in particular a rapid method of screening patients exhibiting diffuse symptoms possible related to food allergy. Thus, there remains a need for a truly rapid, preferably non-invasive method of diagnosing food intolerance and in particular coeliac disease, not involving the need for taking biopsy samples, a preparatory cleaning of the intestines by an enema or other invasive and inconvenient steps, often very exhausting and sometimes even painful for the patient.
SUMMARY OF THE INVENTION
The present invention makes available a rapid and simple method for the diagnosis and/or evaluation of food intolerance, the evaluation of type and/or the degree of severity of a food intolerance condition, in particular coeliac disease, according to the attached claims. According to the invention, rectal NO is measured after provoking the patient rectally with the suspected food intolerance causing agent, and an increased concentration compared to values typical for healthy individuals, or for the same patient at an earlier occasion when said agent was avoided, and an increased value is taken as an indication of food intolerance. Further embodiments and advantages of the present invention will be evident from the description and examples, and the attached figure (
FIG. 1
) which shows the increase factor of a rectal NO response after rectal gluten provocation in 18 patients with diagnosed coeliac disease.
REFERENCES:
patent: 5983899 (1999-11-01), Hällgren
patent: 6183416 (2001-02-01), Alving et al.
patent: 6387890 (2002-05-01), Christianson et al.
patent: 95/32668 (1995-12-01), None
patent: 96/17244 (1996-06-01), None
patent: 98/41153 (1998-09-01), None
Loft et al, Rectal Gluten Challenge and diagnosis of Coeliac Disease, Lancet, vol. 335, Jun. 1990, pp. 1293-1295.*
Smith et al, Nitric Oxide Synthase Activity in Ulcerative Colitis and Crohn's Disease, Lancet, vol. 342, Aug. 1993, pp. 338-340.*
Holmgren Peterson K, et al., “Children with Celiac Disease Express Inducible Nitric Oxide Synthase in the Small Intestine during Gluten Challenge”, J Gastroenterol, vol. 33, 1998, pp. 939-943.
Forte P, et al., “Nitric Oxide Synthesis in Patients with Infective Gastroenteritis”, Gut, vol. 45, 1999, pp. 355-361.
Tomita R, et al., “Role of Nitric Oxide in the Colon of Patients with Ulcerative Colitis”, World J. Surg., vol. 22, 1998, pp. 88-92.
Raab et al., “A Technique for Seqmental Rectaland Colonic Perfusion in Humans”, The American Journal of Gastroenterology, vol.; 87, No. 10, 1992, pp. 14
Alving Kjell
Lundberg Jon
Nordvall Lennart
Weitzberg Edward
Aerocrine AB
Banner & Witcoff , Ltd.
McCrosky David J.
Winakur Eric F.
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