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Zollinger-Ellison syndrome. Clinical presentation in 261 patients.

We prospectively evaluated the initial presenting symptoms in 261 patients with Zollinger-Ellison syndrome (ZES) over a 25-year period. Twenty-two percent of the patients had multiple endocrine neoplasia-type 1 (MEN-1) with ZES. Mean age at onset was 41.1 +/- 0.7 years, with MEN-1 patients presenting at a younger age than those with sporadic ZES (p < 0.0001). Three percent of the patients had onset of the disease < age 20 years, and 7% > 60 years. A mean delay to diagnosis of 5.2 +/- 0.4 years occurred in all patients. A shorter duration of symptoms was noted in female patients and in patients with liver metastases. Abdominal pain and diarrhea were the most common symptoms, present in 75% and 73% of patients, respectively. Heartburn and weight loss, which were uncommonly reported in early series, were present in 44% and 17% of patients, respectively. Gastrointestinal bleeding was the initial presentation in a quarter of the patients. Patients rarely presented with only 1 symptom (11%); pain and diarrhea was the most frequent combination, occurring in 55% of patients. An important presenting sign that should suggest ZES is prominent gastric body folds, which were noted on endoscopy in 94% of patients; however, esophageal stricture and duodenal or pyloric scarring, reported in numerous case reports, were noted in only 4%-10%. Patients with MEN-1 presented less frequently with pain and bleeding and more frequently with nephrolithiasis. Comparing the clinical presentation before the introduction of histamine H2-receptor antagonists (pre-1980, n = 36), after the introduction of histamine H2-receptor antagonists (1981-1989, n = 118), and after the introduction of proton pump inhibitors (PPIs) (> 1990, n = 106) demonstrates no change in age of onset; delay in diagnosis; frequency of pain, diarrhea, weight loss; or frequency of complications of severe peptic disease (bleeding, perforations, esophageal strictures, pyloric scarring). Since the introduction of histamine H2-receptor antagonists, fewer patients had a previous history of gastric acid-reducing surgery or total gastrectomy. Only 1 patient evaluated after 1980 had a total gastrectomy, and this was done in 1977. The location of the primary tumor in general had a minimal effect on the clinical presentation, causing no effect on the age at presentation, delay in diagnosis, frequency of nephrolithiasis, or severity of disease (strictures, perforations, peptic ulcers, pyloric scarring). Disease extent had a minimal effect on symptoms, with only bleeding being more frequent in patients with localized disease. Patients with advanced disease presented at a later age and with a shorter disease history (p = 0.001), were less likely to have MEN-1 (p = 0.0087), and tended to have diarrhea more frequently (p = 0.079). A correct diagnosis of ZES was made by the referring physician initially in only 3% of the patients. The most common misdiagnosis made were idiopathic peptic ulcer disease (71%), idiopathic gastroesophageal reflux disease (GERD) (7%), and chronic idiopathic diarrhea (7%). Other less common misdiagnosis were Crohn disease (2%) and various diarrhea diseases (celiac sprue [3%], irritable bowel syndrome [3%], infectious diarrhea [2%], and lactose intolerance [1%]). Other medical disorders were present in 55% of all patients; patients with sporadic disease had fewer other medical disorders than patients with MEN-1 (45% versus 90%, p < 0.00001). Hyperparathyroidism and a previous history of kidney stones were significantly more frequent in patients with MEN-1 than in those with sporadic ZES. Pulmonary disorders and other malignancies were also more common in patients with MEN-1. These results demonstrate that abdominal pain, diarrhea, and heartburn are the most common presenting symptoms in ZES and that heartburn and diarrhea are more common than previously reported. The presence of weight loss especially with abdominal pain, diarrhea, or heartburn is an important clue suggesting the presence of gastrinoma. The presence of prominent gastric body folds, a clinical sign that has not been appreciated, is another important clue to the diagnosis of ZES. Patients with MEN-1 presented at an earlier age; however, in general, the initial symptoms were similar to patients without MEN-1. Gastrinoma extent and location have minimal effects on the clinical presentation. Overall, neither the introduction of successful antisecretory therapy nor widespread publication about ZES, attempting to increase awareness, has shortened the delay in diagnosis or reduced the incidence of patients presenting with peptic complications. The introduction of successful antisecretory therapy, however, has dramatically decreased the rate of surgery in controlling the acid secretion and likely led to patients presenting with less severe symptoms and fewer complications. (ABSTRACT TRUNCATED)

Abdominal Pain↗

The clinical relevance of lactose malabsorption in irritable bowel syndrome.

OBJECTIVE: The prevalence of lactose malabsorption (LM) in the Caucasian population of northern Europe is estimated to be low. Irritable bowel syndrome (IBS) is a very common diagnosis, and its symptoms are nearly identical to those of LM. Therefore we investigated the prevalence of LM among IBS patients in comparison with healthy volunteers. DESIGN: A double-blind clinical trial compared with healthy controls. SETTING: One out-patient gastroenterology clinic in the Netherlands. PATIENTS: 70 Caucasian IBS patients and 35 healthy volunteers (staff members). METHODS: All 105 underwent hydrogen (H2) breath and blood glucose tests, after an oral intake of 50 grams of lactose. The IBS patients were treated with a lactose-restricted diet for 6 weeks. They completed a lactose intake score before, and a symptom score scored by six separate criteria, before, during and after treatment. RESULTS: In 17 out of 70 (24.3%) IBS patients LM was detected, in comparison with 2 out of 35 (5.7%) controls (P < 0.009). There was no difference in the pre-entry mean lactose intake and symptom score between the LM positive and negative IBS patients. The mean symptom score of the LM positive group showed a marked decrease after 6 weeks of dietary therapy (P < 0.001). CONCLUSION: A substantial number of IBS patients showed a clinically unrecognized lactose malabsorption, which could not be discriminated by symptoms and dietary history, and which can be treated with a lactose-restricted diet. Therefore LM has to be excluded before the diagnosis IBS is made.

Adolescent↗

The effect of a lactose-restricted diet in patients with a positive lactose tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up study.

DESIGN AND METHODS: Prospectively, the effect of a lactose-restricted diet was evaluated among irritable bowel syndrome patients with lactose malabsorption. Lactose malabsorption was defined by a positive hydrogen breath test and a positive blood-glucose test. An analysis of symptoms was completed before, during, 6 weeks after and 5 years after starting the diet. In addition, the number of visits made by the patients to the outpatient clinic was scored during 6 years. RESULTS: In 17 out of 70 irritable bowel syndrome patients (24.3%), lactose malabsorption was detected. There was no difference in the symptom score between patients with a positive lactose tolerance test and patients with a negative lactose tolerance test. After 6 weeks of the lactose-restricted diet, symptoms were markedly improved in lactose malabsorption-positive patients (P < 0.001). After 5 years, one patient was lost for follow-up, and 14 out of the remaining 16 lactose malabsorption patients (87.5%) still had no complaints during the lactose-restricted diet. Two patients chose not to follow the diet continuously and accepted the discomfort caused by lactose intake. Only two out of 16 patients (12.5%) no longer experienced any benefit from lactose restriction. In the 5 years before their diagnosis of lactose malabsorption, these 16 patients visited the outpatient clinic a total of 192 times (mean 2.4 visits per year per person; range 1-7 visits). In the 5 years after diagnosis, they visited the outpatient clinic a total of 45 times (mean 0.6 visits per year per person; range 0-6 visits; P < 0.0001). CONCLUSIONS: In a large majority of irritable bowel syndrome patients with lactose malabsorption, which was previously clinically unrecognized, a lactose-restricted diet improved symptoms markedly both in the short term and the long term. Furthermore, visits by all patients to the outpatient clinic were reduced by 75%. We conclude that diet therapy is extremely cost- and time-saving. Therefore, it is strongly recommended that lactose malabsorption, which is easily treatable, is excluded before diagnosing irritable bowel syndrome.

Adolescent↗

The role of the intestine in bone homeostasis.

The intestine is critical for calcium absorption and skeletal mineralization. Nutritional factors affect the dietary intake of calcium and its bioavailability in the intestine. Individuals differ considerably in their ability to absorb calcium but the reasons for this physiological variation are not fully understood although much is now known about the effects of vitamin D metabolites and the molecular steps in calcium absorption. Bone changes are found in many intestinal disorders including lactose intolerance, coeliac disease, short bowel syndrome, small intestinal bacterial overgrowth and Crohn's disease.

Bone Density↗

Evaluation of a new DNA test compared with the lactose hydrogen breath test for the diagnosis of lactase non-persistence.

BACKGROUND AND AIMS: Recent publications have found that the CC genotype of the DNA variant -13910 T/C upstream of the LCT gene is associated with lactase non-persistence. We therefore compared the value of DNA testing for this variant (DNA test) with the lactose hydrogen breath test (H2 test), which is the clinical standard for the diagnosis of lactase non-persistence. PATIENTS AND METHODS: One hundred and twenty-three consecutive patients with suspected lactose malabsorption were tested for the presence of the -13910 T/C variant by polymerase chain reaction-restriction fragment length polymorphism analysis. These patients also underwent the H2 test after ingestion of 50 g lactose. RESULTS: Thirty-seven subjects had a CC genotype of the -13910 T>C polymorphism suggesting lactase non-persistence; 36 (97%) had also a positive H2 test. Eighty-six subjects had either a TC or a TT genotype suggestive of lactase persistence. Seventy-four (86%) of these tested negative on the H2 test, while 12 patients had a positive H2 test. In eight of these 12 patients duodenal biopsies showed no evidence of small bowel disease. One patient carrying a CC genotype had a negative H2 test. In this patient the rise in serum glucose after oral lactose was normal, furthermore H2 non-excretion was also excluded. CONCLUSIONS: An excellent correlation is observed between a CC genotype and a positive H2 test, whereas the correlation between a TC or TT genotype and a negative H2 test result is less strong. Analysis of the -13910 T/C variant can be considered a good test for predicting the presence of lactase non-persistence in a patient population with suspected lactose malabsorption.

Adolescent↗

Calcium and bone health in children: a review.

The recent national survey shows that dietary calcium intake is variable in children and adolescents, with about half consuming less than the intake recommended by the Recommended Dietary Allowances or the National Institutes of Health Consensus Panel on Optimal Calcium Intake. Osteoporosis is a major disease in adults, resulting in 1.5 million fractures and over $10 billion in medical expenditures annually. Osteoporosis is of growing interest in the research, public health, and health consumer-lay communities and to the many primary care and specialty physicians and other health care professionals who work directly with patients with osteoporosis. Treatment of osteoporosis to prevent fracture is improving with newly introduced medications and approaches, but it is not as effective as needed. Effective prevention strategies are critical to decreasing the morbidity and mortality of the disease. Peak bone mass, obtained during childhood and adolescent growth, is one of the major determinants for the risk of developing osteoporosis and fracture. Genetic potential, gender, ethnic origins, nutritional factors such as calcium and vitamin D intake, growth patterns, and physical activity influence the accretion of bone mineral during childhood and determine the peak bone mass. Randomized, placebo-controlled intervention trials conducted in healthy children who are consuming amounts of dietary calcium in accordance with the US recommendations show that bone mass can be increased by calcium supplementation. Retrospective studies in adults suggest that childhood calcium intake is associated with risk of later osteoporosis and fracture. In addition, common childhood clinical conditions, such as low calcium intake related to lactose intolerance or the use of glucocorticoid medications for chronic illness, are risk factors for the development of osteoporosis in childhood, not just in adulthood. An approach for physicians and other pediatric care providers for screening children for low dietary calcium intake, low bone density, and other osteoporosis risk factors using dual-energy X-ray absorptiometry and the use of calcium supplementation in clinical care are presented.

Adult↗

Soy protein infant formulae and follow-on formulae: a commentary by the ESPGHAN Committee on Nutrition.

This comment by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Committee on Nutrition summarizes available information on the composition and use of soy protein formulae as substitutes for breastfeeding and cows' milk protein formulae as well as on their suitability and safety for supporting adequate growth and development in infants. Soy is a source of protein that is inferior to cows' milk, with a lower digestibility and bioavailability as well as a lower methionine content. For soy protein infant formulae, only protein isolates can be used, and minimum protein content required in the current European Union legislation is higher than that of cows' milk protein infant formulae (2.25 g/100 kcal vs. 1.8 g/100kcal). Soy protein formulae can be used for feeding term infants, but they have no nutritional advantage over cows' milk protein formulae and contain high concentrations of phytate, aluminum, and phytoestrogens (isoflavones), which might have untoward effects. There are no data to support the use of soy protein formulae in preterm infants. Indications for soy protein formulae include severe persistent lactose intolerance, galactosemia, and ethical considerations (e.g., vegan concepts). Soy protein formulae have no role in the prevention of allergic diseases and should not be used in infants with food allergy during the first 6 months of life. If soy protein formulae are considered for therapeutic use in food allergy after the age of 6 months because of their lower cost and better acceptance, tolerance to soy protein should first be established byclinical challenge. There is no evidence supporting the use of soy protein formulae for the prevention or management of infantile colic, regurgitation, or prolonged crying.

Colic↗

Diagnosis and therapy of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most common gut functional diseases, affecting 10-20% of people worldwide. Although most patients do not seek medical help, the disease accounts for huge costs for both patients and health-care systems and worsens significantly patients' quality of life. Diagnosis is based on the identification of symptoms according to Manning, Rome I and Rome II criteria and exclusion of alarm indicators. IBS symptoms overlap with those of coeliac disease, lactose intolerance, food allergies and bile salt malabsorption. The treatment of IBS is centred on an excellent doctor-patient relationship along with drugs targeting the predominant symptom, especially during exacerbations. Current pharmacological remedies are unsatisfactory due to the high number of patients complaining of lack of response and/or symptom recurrence. Although useful in some IBS patients, the validity of psychotherapy deserves further investigation. A wide array of potentially useful drugs are currently under consideration in pre-clinical trials. A better understanding of the pathogenetic mechanisms underlying IBS may help to develop more effective drugs for this disease.

Anti-Bacterial Agents↗

Probiotics and their fermented food products are beneficial for health.

Probiotics are usually defined as microbial food supplements with beneficial effects on the consumers. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks or other fermented foods. Some of the beneficial effect of lactic acid bacteria consumption include: (i) improving intestinal tract health; (ii) enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients; (iii) reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals; and (iv) reducing risk of certain cancers. The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase. Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed. Recent scientific investigation has supported the important role of probiotics as a part of a healthy diet for human as well as for animals and may be an avenue to provide a safe, cost effective, and 'natural' approach that adds a barrier against microbial infection. This paper presents a review of probiotics in health maintenance and disease prevention.

Animals↗

Calcium absorption and calcium bioavailability.

Calcium is important for bone health. It has been customary to focus on dietary calcium intake, but of central importance for the body needs in the individual patient is the actual calcium absorption. This absorption consists of an active vitamin D-mediated component and a passive diffusional component. A number of different methods are available for the evaluation of calcium absorption. At present the calcium absorption tests using calcium isotopes (radioactive or stable) appear to be the most reproducible way of determining calcium absorption. The major nutrient sources for calcium are milk and milk products, whereas some of the green vegetables have a low bioavailability of calcium. When deciding whether an increased calcium intake is advisable, the following questions must be answered. What is the calcium absorptive status of the patient? How should the calcium supplement be dispensed? What calcium salt should be used? When should calcium supplements be taken? What is the compliance of the patient? When should the treatment be evaluated? The calcium supplement might be taken as milk (or milk products) or, in patients with lactose intolerance, as calcium supplements. Quite a number of calcium supplements are available on the market, and many of them are marketed without proper knowledge of the bioavailability of the actual preparation. For the benefit of our patients it is now reasonable to demand such investigations before marketing calcium supplements.

Biological Availability↗

Temproary intestinal lactase deficiency in light-treated jaundiced infants.

The intestinal lactase activity in six newborn jaundiced light-treated infants with diarrhea and in eight normal controls were compared by lactose tolerance test (LTT). The ability to hydrolyze lactose was minimal in the jaundiced infants during light-treatment compared to the controls which could absorb lactose very well. Peroral intestinal biopsies were taken from the newborn jaundiced infants during light-treatment. By histochemical technique no intestinal lactase activity was found in these intestines. When the jaundiced infants with diarrhea were given lactose-free diet, the stools normalized. The effect was reversed when breast milk was given while the baby was still jaundiced and light-treated. These findings indicate that the increased amounts of unconjugated bilirubin in the intestine of jaundiced infants during light-treatment inhibit the intestinal brush-border lactase. When the icterus fades the lactase is again active. The practical consequence is to give light-treated infants lactose-free diet if they get diarrhea, and to reintroduce breast milk or other lactose containing diet when the baby is no longer icteric.

Bilirubin↗

Gut transit time and lactose malabsorption during phototherapy. I. A study using lactose-free human mature milk.

Sixty newborn infants with normal birth weight suffering from uncomplicated hyperbilirubinemia were studied. They were fed human mature milk from which lactose had been eliminated, whereafter either sucrose ("sucrose milk") or lactose ("lactose milk") was added. 30 infants received ordinary phototherapy and 30 intensive phototherapy (blue double light). 15 in each group had "sucrose milk" and 15 "lactose milk". There was no significant difference between the increase in blood glucose (delta BS) by lactose tolerance tests performed before phototherapy (LTT1) and by those performed during phototherapy (LTT11), neither in infants treated with ordinary nor with intensive phototherapy. All infants had normal delta BS-LTT11, except one receiving ordinary phototherapy. There was no significant difference in gut transit time between infants having "sucrose milk" and infants having "lactose milk", neither in those treated with ordinary nor with intensive phototherapy. Gut transit time was significantly shorter in infants treated with intensive phototherapy than in infants treated with ordinary phototherapy without there being any significant difference in delta BS-LTT11. The infant with flat LTT11 may have developed lactose malabsorption during the phototherapy. Thus, lactose malabsorption is not the usual cause of the reduced gut transit time during phototherapy and must be a rare complication in phototherapy.

Bilirubin↗

Gut transit time and lactose malabsorption during phototherapy. II. A study using raw milk from the mothers of the infants.

Thirty newborn infants with normal birth weight suffering from uncomplicated hyperbilirubinemia were studied. 15 infants received ordinary phototherapy and 15 intensive phototherapy (blue double light). All infants received their mothers' milk or fresh milk from mothers of other newborn infants of the same age. All infants had normal lactose tolerance test during the phototherapy, except one infant receiving ordinary transit time was relatively long. The gut transit time was significantly shorter in the infants treated with intensive phototherapy than in those treated with ordinary phototherapy without there being any significant difference in the increase in blood glucose by lactose tolerance tests. It is concluded that lactose malabsorption is not the usual cause of the reduced gut transit time during phototherapy even if the infants receive their mothers' milk.

Bilirubin↗

The status of lactose absorption in Hong Kong Chinese children.

Lactose malabsorption was investigated in 169 Chinese children aged between two and 16 years using the breath hydrogen test. The challenge was either lactose solution (1 g/kg) or cow's milk (10 ml/kg). Overall, 68% of the children showed a significant increase in breath hydrogen following the lactose challenge while only 17% showed an increase after the cow's milk challenge and 13% after both challenges. The number of malabsorbers increased significantly (p less than 0.001) with age and no associated gastrointestinal symptoms or signs were found in any of the children following the challenges, suggesting a gradual and partial loss of intestinal lactase activity. We conclude that the prevalence of lactose malabsorption in Hong Kong children is very high using the standard lactose tolerance test but when a more realistic amount of lactose and a natural medium such as a glass of milk is used as the challenge, the number of malabsorbers becomes small and clinically insignificant.

Adolescent↗

Nutritional aspects of soy formula.

Soy formula is a commonly used alternative to cows' milk formula. While its primary use has been for infants with milk protein allergy and lactose intolerance, soy formula is used increasingly for infants with gastrointestinal discomfort. The nutritional composition of soy formula has been designed to cover the nutrient needs of the newborn infant; however, some aspects of its composition need further consideration. The protein level of soy formula is usually higher than that of milk-based formulae, partially because of differences in protein digestibility and partly because of differences in amino acid composition. The presence of phytic acid in soy formula presents a problem with regard to mineral and trace element bioavailability. Several steps can be taken to minimize this problem, either by reducing the phytate content of soy protein isolate or by changing levels of minerals/trace elements in the formula. Finally, the high levels of manganese in soy formula present a potential problem in that manganese absorption and retention are high during infancy.

Amino Acids↗