Psychiatric, somatic, and gastrointestinal disorders, and Helicobacter pylori infection in children with recurrent abdominal pain.

AIMS: To examine the utility of the Rome II criteria in children with recurrent abdominal pain (RAP) and compare them to those who met Apley's criteria and those who met neither criteria. METHODS: Prospective study in general paediatric clinics in Komagane, Japan. Children with abdominal pain were classified into those who met Rome II criteria, those who met Apley's criteria, and those who met neither. RESULTS: A total of 182 children with RAP participated; 45 children met Rome II criteria, 55 met Apley's criteria, and 82 met neither. Children who met Rome II criteria had a significantly higher prevalence of psychiatric and somatic disorders compared to the group met neither (36% v 6%, 22% v 10%, respectively). The overall prevalence of H pylori was 7%; prevalence increased with age from 3% at age < or = 10 to 10% for children >10 years. Children who met Rome II criteria had a significantly higher prevalence of H pylori infection than the reference group (18% v 4%). In a logistic regression model, all the study variables were included in the model specifying first the Rome II criteria group as the independent variable; psychiatric disorders, H pylori infection, and older age group were independent risk factors. CONCLUSIONS: More than half the children suffering from recurrent abdominal pain met neither Apley's nor Rome II criteria. Children who meet Rome II criteria should be evaluated for psychiatric disorders and should be tested for H pylori infection. Despite the overall trend for a fall in the prevalence of H pylori infection among children in Japan, there are subpopulations of sick children where the prevalence of the infection is relatively high.

[Helicobacter pylori infection in a group of symptomatic and asymptomatic children and adolescents in the Czech Republic]. / Infekce Helicobacter pylori u souboru symptomatických a asymptomatických detí a dospívajících v Ceské republice.

BACKGROUND: There exist only inconsistent results of studies on the relationship between Helicobacter pylori (H. pylori) infection and functional dyspepsia and/or recurrent abdominal pain in children and adolescents. The answer could bring a comparison of the epidemiological features of H. pylori infection between children and adolescents with dyspepsia and/or recurrent abdominal pain (symptomatic) and without these symptoms (asymptomatic), living in the Czech republic. METHODS AND RESULTS: Study includes children and adolescents (2-18 years) with upper gastrointestinal symptoms visiting paediatric gastroenterology department between 1994 and 1999. Age, sex, socioeconomic level matched control (asymptomatic) group consisted of children and adolescents visiting the general paediatric service with symptoms not related to the upper gastrointestinal tract. Demographic and socioeconomic factors, including parent(s) educational level, place of residence, living conditions, type of drinking water and pets in their household were evaluated. Serum of the children and adolescents was tested for H. pylori IgG by enzyme linked immunosorbent assay. In addition, the symptomatic children and adolescents underwent endoscopic examination and biopsies from gastric antrum and corpus were taken for the quick urease test, histology/histoscopy, and H. pylori cultivation. H. pylori infection in this group was stated when at least two tests were positive. Altogether 829 children and adolescents were examined, 624 cases were symptomatic and 205 represented controls (asymptomatic). The prevalence of infection was 33% among symptomatic children vs. 7.5% among controls (OR = 6.2, p.001) and was similar among boys and girls (32% vs. 34.5%, respectively). H. pylori prevalence increased with age among symptomatic children (10% for children below 6 years and 37% between 11 to 16 years) (p.001). In contrary, prevalence tended to fall with age among asymptomatic children (11% in children below 6 years vs. 6% in children over 10 years (OR = 2.0, 95% CI = 0.7-6.2). In both groups, an inverse correlation between H. pylori occurrence and mother's educational level was observed. The H. pylori incidence was 10% among asymptomatic children who drank water from municipal water supply or from a well vs. 3% among those who drank bottled water (OR = 4, 95% CI = 1.1 to 18, p.05). CONCLUSIONS: H. pylori infection was more prevalent among symptomatic children and adolescents vs. asymptomatic children and adolescents within the same population. H. pylori incidence increased with age among symptomatic children and adolescents and tended to fall among controls, showing deep differences between the two groups. With exception of the bottled water drinking, presence of any other factor studied represented significant risk for acquiring the H. pylori infection.

Simplified 13C-urea breath test for detection of Helicobacter pylori infection.

OBJECTIVE: The U.S. standard 13C-urea breath test (13C-UBT) has proven to be extremely reliable but entails several complicated performance requirements and a test period of approximately 1 h. The aim of this study was to compare the standard 13C-UBT with a simplified version embodying modifications of test meal, duration of fasting, amount of 13C-urea, method of breath collection, and duration of test. METHODS: This was a randomized, three-way, crossover study of the standard U.S. 13C-UBT, which contains 125 mg of 13C-urea and a pudding test meal. The final breath sample is taken 30 min after urea ingestion. This test was compared with a formulation containing 75 mg of 13C-urea, a 2.5-g citric acid test meal (UBT-Lite), and a final breath sample taken by direct exhalation into tubes 15 min after urea ingestion. We also compared the effect of prior meals versus fasting on the test outcome with the UBT-Lite. RESULTS: A total of 259 subjects were enrolled in the trial, and 249 completed all three urea breath tests. There was excellent agreement between the three versions of the UBT with >98% of subjects having concordant results. Using predetermined criteria, there was substantial equivalence between the tests. Neither solid and/or liquid food up to 1 h before performing the UBT-Lite affected outcome. CONCLUSION: The UBT-Lite formulation of the 13C-UBT proved to be an improved version of the U.S. standard 13C-UBT offering less expensive ingredients, shorter test duration, and a simplified breath test collection method, without sacrificing accuracy.

Pattern of primary resistance of Helicobacter pylori to metronidazole or clarithromycin in the United States.

BACKGROUND: Therapy for Helicobacter pylori is generally empiric despite the fact that resistance to metronidazole and clarithromycin compromise therapeutic efficacy. The aim of this study was to aid clinicians in choosing a course of therapy for H pylori infection in the United States. METHODS: The frequency of primary clarithromycin and metronidazole resistance among H pylori isolated from patients enrolled in US-based clinical trials between 1993 and 1999 was reviewed in relation to patient age, sex, region of the United States, and test method (Etest and 2 agar dilution procedures). RESULTS: Clarithromycin and metronidazole resistance rates were based on the results of 3439 pretreatment Etest determinations and 3193 agar dilution determinations. Sex and age were available on 900 and 823 individuals, respectively. Metronidazole resistance was 39% by Etest and 21.6% by agar dilution (P<.001). Clarithromycin resistance was 12% by Etest and 10.6% by agar dilution. Amoxicillin or tetracycline resistance was rare. Metronidazole and clarithromycin resistance was more common in women than men (eg, 34.7% vs 22.6% for metronidazole and 14.1% vs 9.7% for clarithromycin (P =.01 and P =.06, respectively). Antibiotic resistance increased gradually up to age 70 years, then declined significantly (P<.05) regardless of test method. Regional differences in antimicrobial resistance did not occur. CONCLUSIONS: While age and sex had significant effects on resistance rates, regional differences were not present. The high prevalence of resistance to metronidazole and clarithromycin may soon require the performance of antimicrobial susceptibility testing of H pylori isolates prior to initiating treatment.

Helicobacter pylori infection in preschool and school-aged minority children: effect of socioeconomic indicators and breast-feeding practices.

Helicobacter pylori infection was examined among 356 asymptomatic white Hispanic and black children aged 2--16 years attending 13 licensed day care centers in Houston. Demographic information and socioeconomic factors were evaluated. H. pylori status was determined by (13)C-urea breath testing. The prevalence of active H. pylori infection was 24% and increased with age. Prevalence was almost identical among white Hispanic and black children. Children living in the most crowded conditions were at the greatest risk for H. pylori acquisition, and an inverse correlation was seen between the mother's education and H. pylori positivity in children. Breast-feeding played a protective role against the acquisition of H. pylori infection. Understanding the epidemiology of H. pylori infection in childhood requires better understanding of the interactions between environment, ethnic group, and socioeconomic conditions.

Alendronate and naproxen are synergistic for development of gastric ulcers.

BACKGROUND: Both alendronate sodium use and nonsteroidal anti-inflammatory drug use are associated with gastric ulcers. The aim of this study was to investigate whether alendronate and naproxen are synergistic as causes of gastric ulcers. METHODS: We performed an endoscopist-blind, randomized, crossover, single-center comparison of 10 mg/d of alendronate sodium, 500 mg of naproxen sodium twice daily, or the combination taken orally for 10 days in volunteers aged 30 years or older. Videoendoscopy was used to evaluate the presence and degree of mucosal damage to the esophagus, stomach, or duodenal bulb before and after each treatment. There was a 1- to 4-week washout between evaluations. RESULTS: Twenty-six healthy volunteers participated (18 women and 8 men), aged 30 to 50 years. Gastric ulcers were present in 2 subjects receiving alendronate (8%), in 3 receiving naproxen (12%), and in 10 receiving both (38%) (P<.05 for the combination vs either drug alone). CONCLUSIONS: Both alendronate and naproxen can cause gastric ulcers. The combination appears synergistic. Alendronate should be used with caution in those who simultaneously require nonsteroidal anti-inflammatory drugs.

Balloon-type versus non-balloon-type replacement percutaneous endoscopic gastrostomy: which is better?

Percutaneous endoscopic gastrostomy (PEG) has been an established procedure for nearly 20 years. Caring for patients with a PEG has been incorporated into the practice of nurses in most gastroenterology settings. Several practice-related questions have arisen, particularly in relation to replacement PEGs. In an attempt to obtain relevant information for decisions relating to cost-effectiveness and providing optimum care for PEG replacement, two clinical research questions were studied: (1) is there a difference in patient (stomal) response related to two different replacement PEG tubes, and (2) is there a difference in the duration (life-span) between the two types of replacement tubes? A non-experimental, two-group descriptive study was conducted to answer the two clinical research questions. Two types of replacement PEG tubes were evaluated: a balloon type and a non-balloon type. Stoma response (recording skin and insertion site characteristics) and PEG life span were the measures of interest. Differences in the occurrence of skin and insertion site problems between the two groups were not statistically significant. Differences between the life spans of the two tubes were found to be statistically significant at three time intervals. Findings give information to the practitioner involved in making independent and interdependent practice decisions when planning care for patients with a PEG. Suggestions for additional research and replication are included.

An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae.

OBJECTIVES: The nitrogen-containing bisphosphonates alendronate and risedronate have been reported to have upper gastrointestinal (GI) safety and tolerability profiles comparable to those of placebo. Nevertheless, both agents have demonstrated similar potential for irritation of gastric mucosa at high doses in preclinical studies. The present study compared the potential for alendronate and risedronate to produce endoscopic upper GI mucosal irritation using the highest approved dosage regimens for the two agents. METHODS: This was a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial in which a total of 235 patients (men or postmenopausal women, aged 45-80 yr) with normal upper GI endoscopy at baseline received 28-day treatments with the following: alendronate 40 mg/day (N = 90), risedronate 30 mg/day (N = 89), placebo (N = 36), or placebo with aspirin 650 mg q.i.d. for the last 7 days (N = 20). Endoscopy was repeated on day 29 using standardized scoring scales. RESULTS: After 28 days of treatment, the alendronate and risedronate groups had comparable mean gastric and duodenal erosion scores that were significantly lower than those of the aspirin group. Esophageal scores were comparable in all groups. Gastric ulcers and/or large numbers of gastric erosions occurred in approximately 3% of alendronate and risedronate patients versus 60% with aspirin. Both bisphosphonates were clinically well tolerated. CONCLUSIONS: The potential for gastroduodenal irritation is similar for alendronate and risedronate and is markedly less than for aspirin. The findings of this study, together with the large placebo-controlled clinical trial experience with both agents and extensive epidemiological data for alendronate, suggest that the risk for clinically important gastric irritation with these bisphosphonates is very low, even at the highest available doses.

Helicobacter pylori infection in children of Texas.

BACKGROUND: Acquisition of the Helicobacter pylori infection usually occurs in childhood. The prevalence of infection differs among ethnic groups and in adults is inversely related to the socioeconomic status of the individual's family during childhood. This study investigates the seroprevalence of H. pylori infection in children of different ethnic groups in relation to socioeconomic class and investigates the prevalence of acute H. pylori infection among children who have had recent onset of abdominal pain. METHODS: Serum samples were collected from 797 children, aged 6 months to 18 years, of various socioeconomic and ethnic backgrounds, at a large urban children's hospital. H. pylori status was determined by an anti-H. pylori immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) validated for pediatric use. To determine the prevalence of acute H. pylori infection, children brought to the emergency center with abdominal symptoms without diarrhea and overt signs of acute abdomen were evaluated with both serology and the 13C-urea breath test. Acute H. pylori was defined as a positive 13C-urea breath test result and negative IgG serology for H. pylori. RESULTS: The overall seroprevalence of H. pylori was 12.2% and increased with age (e.g., 8.3% at 6-11.9 months and 17.9% at 13 years). The prevalence was inversely related to socioeconomic status (6.6%, moderate to high vs. 15%, low socioeconomic status). The difference in seroprevalence among blacks (16.8%), Hispanics (13.3%), and whites (8.3%; P < 0.01) could be accounted for by differences in socioeconomic status. Eighteen percent of children who were evaluated at the emergency center for recent-onset abdominal pain had acute H. pylori infections. CONCLUSIONS: Socioeconomic status, not ethnic group, is the more important risk factor for acquisition of H. pylori infection during childhood. Acute H. pylori infection was a relatively common cause of recent-onset, nonsurgical abdominal pain.

Helicobacter pylori infection and eradication in paediatric patients.

Helicobacter pylori is now recognised to be typically acquired during childhood. Studies also indicate that the infection is frequently lost in childhood; however, it is still unclear whether this is related to the use of antibacterials, the natural history of the infection, or both. H. pylori colonises gastric mucosa and is causally related to chronic gastritis and peptic ulcer disease in both children and adults. Successful eradication of H. pylori has resulted in the healing of duodenal ulcers and the lowering of the ulcer relapse rate in children. Therapy to cure the infection should be started in all children with peptic (duodenal or gastric) ulcer who are still infected. The ideal anti-H. pylori regimen should be safe, cheap, easy to comply with, well tolerated by children and able to achieve a high cure rate. Although US data are lacking, it is anticipated that the treatment regimen for children should be similar to that in adults (a triple therapy regimen that combines a proton pump inhibitor with 2 antimicrobial agents for 14 days). It is inappropriate to prescribe anti-H. pylori therapy without a firm diagnosis. The use of multiple antibacterials in a paediatric patient with an ulcer but without H. pylori infection cannot provide any benefit to the patient or the community. Such an approach only provides the possibility for adverse effects, for example development of antibacterial resistance among bystander bacteria. It is very important to confirm the diagnosis of H. pylori infection. The [13C]urea breath test is the noninvasive method of choice to determine H. pylori status in children and the ideal test for post-therapy testing. There is a need for post-therapy confirmation because of the likelihood of poor outcome for some treatment regimens, which is why post-therapy testing should be the standard of care. There is weak and inconsistent evidence of an association between H. pylori infection and recurrent abdominal pain (RAP) in children, in part because of the unclear definition of RAP in the literature. Therefore, there is still considerable debate regarding the treatment of infected children with RAP.

Helicobacter pylori infection in asymptomatic children: comparison of diagnostic tests.

BACKGROUND: Childhood is known to be a major risk period for acquiring Helicobacter pylori infection. Studies of the epidemiology of H. pylori infection depend on the validity of the diagnostic tools used to detect the infection in the pediatric setting. This study aims to conduct a combination of diagnostic tests on the same children, evaluate the sensitivity and the specificity of IgG antibody testing compared with the 13C-urea breath test, and examine the variability in the prevalence of H. pylori infection in asymptomatic children based on the use of different diagnostic tests. METHODS: 13C-urea breath test (13C-UBT), whole blood FlexSure (systemic antibodies), and OraSure (salivary antibodies) tests were conducted on 287 asymptomatic children (151 boys, 136 girls; ages 2-18 years). The three tests were conducted on each child during the same day. The prevalence was calculated using each test independently. RESULTS: H. pylori infection was detected in 32%, 22%, or 18% of the studied children, based on UBT, OraSure, or FlexSure, respectively. A total of 103 children tested positive for any one test (92 on UBT, 8 on FlexSure, 3 on OraSure), giving a prevalence of 35% based on the "parallel" method. Only 39 children tested positive in all three tests, giving a prevalence of 14% based on the "serial" method. Using the UBT as the gold standard, the sensitivity of FlexSure and OraSure were 48% and 65%, respectively, and the specificity of both tests was greater than 95%. When we applied the parallel method, the sensitivity and specificity of the combined antibody tests (FlexSure + OraSure) compared to the UBT were 71% and 95%, respectively. CONCLUSIONS: Among asymptomatic children, there is a wide variation in the prevalence of H. pylori infection based on the diagnostic test used. The study shows that antibody assays are less suitable than the UBT. However, under certain conditions, the IgG assays (combined systemic, salivary, or both) are less expensive alternative tools to the UBT for epidemiological studies in children.

Characterization of a culture method to recover Helicobacter pylori from the feces of infected patients.

BACKGROUND: Helicobacter pylori is difficult to culture from stool. Multiple efforts from multiple laboratories have been unsuccessful, and the optimal conditions to recover H. pylori from stool are still not known. Recovery of H. pylori from feces of infected individuals is important for the performance of molecular epidemiological investigations, especially in children, where their symptoms do not warrant endoscopy to recover the organism. METHODS: Fresh fecal specimens (noncathartic) were obtained from 19 known H. pylori-infected patients and were processed to recover the organism. Fresh fecal specimens (noncathartic) were also obtained from three known H. pylori-negative individuals (controls) to determine whether H. pylori could be isolated from stools seeded with known concentrations of the organism. Treatment of the fecal suspensions with cholestyramine, a basic anion exchange resin that binds bile acids, was used in an attempt to enhance recovery of H. pylori by sequestering bile acids that are inhibitory to H. pylori growth. H. pylori was identified based on colony morphology, cell morphology, Gram's stain, biochemical reactions, and polymerase chain reaction for two H. pylori genes. RESULTS: Among 19 patients, H. pylori was cultured at least once from 3 and three times from 2 (5 of 19). Feces that were seeded with H. pylori and obtained from three H. pylori-negative volunteer controls yielded positive recovery in all instances. CONCLUSION: We have confirmed that it is possible to culture H. pylori from human stool, but the procedure for optimal recovery has still not been defined.

Conservation of Helicobacter pylori genotypes in different ethnic groups in Houston, Texas.

This study was concerned with whether the Helicobacter pylori strains circulating among ethnic groups living in the same region differ. The polymerase chain reactions to genotype (cagA, vacA, and iceA) H. pylori isolates from healthy volunteers from 4 ethnic groups (black, n=35; white Hispanic, n=31; whites, n=30; Vietnamese, n=29) residing in Houston were examined. The Vietnamese volunteers had the "East Asian"-type cagA 3' repeat region structure, and the others had the "non-Asian" type. The most common genotypes were delineated as follows: blacks and Hispanics, cagA+, vacA s1b-m1, and iceA2; whites, cagA+, vacA s1a-m2, and iceA2; and Vietnamese, cagA+, vacA s1c-m2, and iceA2. Two Hispanic families were also examined. H. pylori isolates from the children and their mothers had the same genotype and were different from those associated with the children's fathers or brothers-in-law. Conservation of an H. pylori genotype within ethnic groups over the course of generations will prove useful for epidemiological study of the coevolution of humans and H. pylori.

Diabetes mellitus and Helicobacter pylori infection.

Alterations of glucose metabolism in diabetes have been suggested as promoting Helicobacter pylori colonization. We performed a cross-sectional sero-prevalence study of diabetic patients (insulin-dependent, or type 1, and non-insulin-dependent, or type 2, diabetes mellitus) with H. pylori and compared them with a control group. Consecutive diabetic outpatients aged 12 to 75 y and with disease duration of greater than 1 y were enrolled. Helicobacter pylori status was evaluated by using an enzyme-linked immunosorbent assay for anti-H. pylori immunoglobulin G. Demographic data were obtained from each individual, and socioeconomic class was assessed by occupation and education level. A total of 891 individuals participated (240 with type-2 diabetes, 145 with type-1 diabetes, and 506 control subjects). After controlling for age, there was no significant difference in the prevalence of H. pylori infection in any age group. In fact, the prevalence of H. pylori was numerically higher among children in the control group than among children with type-1 diabetes (25% versus 9%, respectively; P = 0.1). Previous associations of H. pylori and diabetes may have arisen from failure to consider socioeconomic status or age. Because childhood is the most common period for acquisition of H. pylori infection, the higher prevalence of infection among the normal children as opposed to those with type-1 diabetes confirms the lack of an association.

Evidence from a nine-year birth cohort study in Japan of transmission pathways of Helicobacter pylori infection.

We examined the longitudinal changes of Helicobacter pylori infection within 46 families with children and 48 couples without children living in Japan. The study cohort was monitored from 1986 to 1994. H. pylori status was assessed by the presence of anti-H. pylori immunoglobulin G antibodies. At study entry, H. pylori prevalence in children with positive mothers was 23% versus 5% in children with negative mothers (odds ratio = 5.3; 95% confidence interval = 0.6 to 42.8). Seroconversion (rate of 1.5%/year) was evident only among children living with positive mothers and did not differ among adults living with or without children. These data strongly support the cluster phenomenon of H. pylori infection among families, the key role of the infected mothers in the transmission within families, and the importance of adult-child transmission and not vice versa.

Are genetic influences on peptic ulcer dependent or independent of genetic influences for Helicobacter pylori infection?

BACKGROUND: Genetic factors play a role or roles in the etiology of peptic ulcer disease and the acquisition of Helicobacter pylori infection. OBJECTIVE: To evaluate the relative importance of genetic and environmental influences as well as the importance of H. pylori on peptic ulcer disease. DESIGN: Cross-sectional study on monozygotic (MZ) and dizygotic (DZ) twins, reared apart or together. PARTICIPANTS: Twins of the subregistry of the Swedish Twin Registry included in the Swedish Adoption/Twin Study of Aging. MEASUREMENTS: Peptic ulcer disease and H. pylori status were assessed in MZ and DZ twin pairs reared apart or together. A total of 258 twin pairs had information regarding H. pylori status and history of peptic ulcer. Helicobacter pylori status was assessed as the presence of anti-H. pylori IgG. RESULTS: The intraclass correlations for peptic ulcer disease for MZ twins reared apart and together and DZ twins reared apart and together were 0.67, 0.65, 0.22, and 0.35, respectively, which indicates that genetic effects are important for liability to peptic ulcer. The correlation coefficient for MZ twins reared apart (0.67) provides the best single estimate of the relative importance of genetic effects (heritability) for variation in liability to peptic ulcer disease, and structural model fitting analyses confirmed this result (heritability, 62%). The cross-twin cross-trait correlations for MZ and DZ twins were examined to determine whether genetic effects for peptic ulcer were shared with or independent of genetic influences for H. pylori. The cross-correlations for MZ and DZ twins were almost identical (0.25 and 0.29, respectively), suggesting that familial environmental rather than genetic influences mediate the association between peptic ulcer disease and H. pylori infection. CONCLUSIONS: Genetic influences are of moderate importance for liability to peptic ulcer disease. Genetic influences for peptic ulcer are independent of genetic influences important for acquiring H. pylori infection.

Normalizing results of 13C-urea breath testing for CO2 production rates in children.

BACKGROUND: The 13C-urea breath test detects the presence of Helicobacter pylori from an enrichment of breath 13CO2, which, in turn, is critically dependent on the amount of dilution by endogenous CO2 production. The production of CO2 differs according to age (adults > children), sex (male > female) weight, and height. The cutoff value of 2.4 delta%(delta over baseline, DOB) for the 13C-urea breath test, defined in adults, does not take into account actual CO2 production. Therefore, this cutoff value (2.4 delta%) may or may not be appropriate for children. The purpose of this study was to determine a cutoff value that would provide accurate results in pediatric patients, independent of their differences in anthropometric parameters. METHODS: Estimates of CO2 production were combined with DOB values to calculate the host-dependent urea hydrolysis rate. RESULTS: Calculated as urea hydrolysis rate, the cutoff range for adults was 10.4 to 10.9 microg/min. Individual ranges were concentric (men, 9.6-10.9 microg/min; women, 8.5-12.2 microg/min). Results in studies of 312 children show that a urea hydrolysis rate of more than 10 m microg/min may also be appropriate to predict H. pylori infection. CONCLUSION: Calculating 13C-urea breath test values as urea hydrolysis rate removes the effect of individual anthropometric differences on test outcome and provides a single cutoff value for pediatric patients of all ages.

Interaction of alcohol and hepatitis C virus infection on severity of liver disease.

Chronic alcoholics have a high prevalence of hepatitis C virus (HCV) infection. The present study was carried out to examine the association between HCV infection and alcohol abuse, and the influence of these factors on the severity of liver disease. Patients with history of heavy alcohol abuse (> or = 80 g of ethanol per day for > or = 5 years) were analyzed with respect to the amount of alcohol use, clinical evidence of liver disease, and laboratory tests. One hundred ninety-nine patients, 137 HCV positive and 62 HCV negative were included in the study. HCV-infected subjects had liver disease for a longer duration (P < 0.0001) and had higher incidence of symptoms of hepatic decompensation in the past compared to uninfected alcoholics. Several differences were noted between the two groups at the time of presentation to the hospital. Alcoholics with HCV infection had lower daily alcohol consumption (P < 0.001), were abstinent for a longer duration (P < 0.02) and had lower lifetime use of ethanol (P < 0.005) compared to HCV-negative subjects. Assessment of liver tests showed greater derangement in uninfected alcoholics compared to HCV-positive subjects. The present study shows that HCV-infected chronic alcoholics have lower alcohol consumption and, perhaps as a consequence, have less severe liver disease compared to HCV-negative individuals. These findings suggest that in chronic alcoholics, despite the presence of HCV infection, the severity of liver damage is related to the amount of alcohol consumption.

Citric acid as the test meal for the 13C-urea breath test.

OBJECTIVE: Test meals are used in the urea breath test to slow gastric emptying and to increase the area of contact with the substrate. Recently, citric acid has been suggested as an improved liquid test meal. The mechanism is unknown and could act by delaying gastric emptying, decreasing the pH at the site of the bacteria, or both. Our aim was to evaluate the effects of citric acid test meals on urea hydrolysis in vivo, to identify the possible mechanism for enhanced urea hydrolysis, and to identify the minimum effective dose. METHODS: We compared the U.S. commercial 13C-urea breath test with four liquid test meals (200 ml of water) consisting of citric acid, ascorbic acid, sodium citrate, and glucose polymer and also after the subcutaneous administration of pentagastrin. We studied healthy volunteers with and without proven H. pylori infection (by serology and histology). 13C-urea was administered orally simultaneously with the liquid test meals or immediately after the pudding had been ingested. Breath samples were taken before and after oral administration of the 13C-urea. RESULTS: A dose response in urease activity was evident as the amount of citric acid was increased from 1 to 4 g. Citric acid at 1, 2, or 4 g produced significant increases in breath 13CO2 activity, compared with the commercial pudding (p < 0.05). Ascorbic acid (p = 0.053), subcutaneous pentagastrin (to lower pH) (p = 0.199), and glucose polymer (p = 0.03) (to delay gastric emptying) all approximately doubled breath 13CO2, compared with the commercial kit. Nevertheless, the increases were all significantly less than with the 4 g citric acid test meal. CONCLUSIONS: The data are consistent with the marked effect of citric acid on gastric emptying and, possibly, distribution of the urea within the stomach being largely responsible for the enhanced urease activity with citric acid test meals. It should be possible to use a low dose of citric acid (e.g., 1 g per 200 ml) to enhance the simplicity and palatability of the test.

Alendronate gastric ulcers.

BACKGROUND: It appears likely that drugs other than NSAIDs may cause ulcers and ulcer complications (e.g. potassium chloride). Alendronate (Fosamax) is used in the treatment and prevention of metabolic bone disease and has also been associated with severe oesophageal damage and stricture. We have previously shown that the dose of alendronate used for Paget's disease (40 mg) causes gastric damage similar to NSAIDs. The usual dose for the treatment of postmenopausal osteoporosis is 10 mg per day. AIM: To investigate whether the 10 mg dose of alendronate causes gastric ulcers. METHODS: We performed an endoscopist-blind, crossover, randomized, single-centre comparison of 10 mg of alendronate/day and placebo in volunteers aged 40 years or more. Video-endoscopy was used to evaluate the presence and degree of mucosal damage to the oesophagus, stomach, or duodenal bulb after 7 and 14 days of treatment. RESULTS: Twenty-four healthy volunteers participated, including 15 women and nine men, ranging in age from 41 to 52 years. Visible gastric mucosal damage was present in nine (38%) who received alendronate compared to three (13%) in the placebo group. There was a marked difference in the severity of mucosal damage; there were no ulcers or large erosions in those receiving placebo. In contrast, potentially clinically significant gastric mucosal injury was seen in six subjects receiving alendronate (two developed antral ulcers and four had large (4-8 mm) superficial antral erosions) compared to none in the placebo group (P = 0.0219). One subject developed oesophageal damage in the form of multiple linear superficial erosions in the mid and distal oesophagus. Duodenal injury was not seen. CONCLUSION: Alendronate causes gastric ulceration, suggesting that alendronate use may be associated with ulcer complications such as acute upper gastrointestinal bleeding. The results of this study suggest the need for post-marketing surveillance to clarify the nature, frequency and magnitude of any potential gastrointestinal side-effects associated with the use of this drug.