13C-Octanoic acid breath test: valueless test for gastric emptying?
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Biomedical subjects
Publications and source records attributed to A Andriulli.
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BACKGROUND/AIMS: This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values. METHODS: A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included. RESULTS: We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis. CONCLUSIONS: These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.
An increasing body of evidence supports the concept of genetic heterogeneity within inflammatory bowel disease (IBD). In this study, a polymorphism of the motilin gene, which determines an amino acid substitution in the motilin protein, has been investigated in IBD patients. Fifty patients with ulcerative colitis (UC), and 52 with Crohn's disease (CD) were investigated for anti-neutrophil cytoplasmatic antibodies (ANCA) and the polymorphism in the second exon of the motilin gene. Sixty unrelated blood donors served as controls. ANCA were found in 30% of UC and 13% of CD. In controls the DNA polymorphism identified two alleles (1 and 2) at a frequency of 42% and 58%, respectively. Patients with either UC or CD showed a slight increase in the frequency of allele 2 (69% and 60%, respectively; P > 0.05 vs controls). This allele was predominant in ANCA-positive CD patients (86%; P < 0.04) while in UC it did not differ. All ANCA-positive CD patients had the disease confined to the colon. A polymorphism of second exon of the motilin gene, leading to a protein variant, is significantly more frequent in the subset of ANCA-positive CD patients. This subgroup of patients appears to share peculiar genetic and clinical features.
BACKGROUND: Autodigestion of the pancreas, secondary to the activation of digestive enzymes, is the pathogenetic mechanism of acute pancreatitis (AP). AIM: Clinical trials in which somatostatin (SS), octreotide (OCT) and gabexate mesilate (FOY) were used to treat patients with AP, were submitted to a meta-analytical evaluation. Five end-points were evaluated: early and overall mortality, patients with complications, complication rate, and patients who needed surgery. RESULTS: In mild AP, no agent proved of value. In severe AP, both SS and OCT were beneficial in improving the overall mortality: the odds ratios (OR) were, respectively, 0.36 (95% CI: 0.20-0.64, P = 0.001) and 0.57 (95% CI: 0.35-0.88, P = 0.006). FOY had no effect on either early or overall mortality, but was effective in improving complication rate (OR = 0.70, 95% CI: 0.56-0.88, P = 0.02), number of patients with complications (OR = 0.61, 95% CI: 0.41-0.91, P = 0.01), and number of cases submitted to surgery (OR = 0.60, 95% CI: 0.39-0.92, P = 0.01). SS and OCT had no effect on these latter outcomes. CONCLUSIONS: Antisecretory agents, such as SS and OCT, are able to reduce mortality without affecting complications, whereas antiproteases, such as FOY, have no effect on mortality but do reduce complications. A trial exploring the efficacy of combining antisecretory agents with antiproteases would be of great benefit in patients with severe AP.
BACKGROUND: The urea breath test (UBT) has been proposed as the most accurate test for diagnosing Helicobacter pylori infection. The aim of this work was to evaluate the accuracy of the UBT and to compare the results with histologic and endoscopic findings in H. pylori infected patients. METHODS: One-hundred-and-seventy-two consecutive dyspeptic outpatients were studied by means of endoscopy (with histology and culture), UBT (75 mg 13C-urea), and serology. Gastritis was classified in accordance with the Sydney criteria. In H. pylori positive patients, the bacterial load was assessed semiquantitatively, the number of bacteria in histologic specimens being counted. UBT results were expressed either as percentage cumulative dose of 13CO2 excreted at 1 h (CD60) or delta over baseline at 30' (DOB30). RESULTS: Of 172 patients, 126 (73%) were H. pylori positive on histology or culture. Using a cut-off value of 3.3/1000 for DOB30, the sensitivity, specificity and accuracy of the UBT were 96%, 93.5%, and 95.3%, respectively. A significant correlation was observed between DOB30 values and intragastric bacterial load (r = 0.32). Moreover, a significant difference in DOB30 values was found between patients sorted by the depth of inflammation (chi(2) = 4.36, p = 0.036). No correlation was observed between DOB30 and endoscopic findings in H. pylori positive subjects. CONCLUSIONS: The UBT is an accurate non-invasive diagnostic tool and can be used to predict both the intragastric bacterial load and the severity of related gastritis.
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BACKGROUND: Helicobacter pylori infection is generally acquired early in life. However, it is still unknown whether a spontaneous eradication can occur. The purpose of this study was to evaluate whether H. pylori infection can undergo spontaneous eradication in children. METHODS: Three hundred and four Italian children (age range, 4.5 to 18.5 years) were tested for H. pylori by means of 13C-urea breath test. Infected children were followed up every 6 months for as long as 2 years. Parents were instructed to record consumption of antibiotics. At each visit, children underwent a repeat 13C-urea breath test. RESULTS: Eighty-five out of 304 (27.9%) children were H. pylori infected. Forty-eight out of 85 infected children (56.4%) participated in the follow-up study. After 2 years, 8 (16.6%) infected children had negative results on 13C-urea breath tests; 2 of them were given antibiotics for concomitant infections. One child was negative at 6 months but became positive again at the next 6-month 13C-urea breath test. Forty children remained persistently positive; of them, 10 were treated with a short course of antibiotics. CONCLUSIONS: Our findings support the hypothesis that, at least during childhood, H. pylori infection may be a fluctuating disease with spontaneous eradication and possible recurrence.
BACKGROUND: In patients with celiac disease, the occurrence of exocrine pancreatic insufficiency has been related to an impairment of the gut-mediated stimulatory effect of the meal on the pancreas. The purpose of this study was to assess the intraduodenal lipase activity in patients with celiac disease by means of the 13C mixed-triglyceride breath test and to monitor pancreatic function after the institution of a gluten-free diet. METHODS: Seventeen untreated patients with celiac disease (mean age, 17.4 +/- 10.5 years) were studied. After an overnight fast, patients were given a standard test meal consisting of 100 g of white bread and 0.25 g of butter per kilogram of body weight, to which 16 mg di-stearyl-13C-octanoyl-glyceride (mixed triglyceride) had been added. Breath samples were taken twice at baseline and at 30-minute intervals for 6 hours after the meal. 13C enrichment in breath was determined by means of Isotope Ratio Mass Spectrometer (IRMS) (ANCA-NT; Europa Scientific, Crewe, UK). Results were expressed as the maximum percentage of 13C recovery per hour at any time, the time to reach peak excretion of 13C, and the percentage of 13C cumulative dose over 6 hours. RESULTS: Mixed-triglyceride breath test results were pathologic in three patients and at the lower limit of the normal range in another patient. In the remaining 13 patients, the results were within normal values. At the 6- and 12-month follow-ups, all patients showed normal intraduodenal lipase activity. CONCLUSIONS: In approximately 24% of patients with celiac disease, the intraduodenal pancreatic lipolytic activity is impaired. The mixed-triglyceride breath test could be used to assess fat maldigestion and to monitor the need for enzyme replacement therapy in such patients.
OBJECTIVE: Functional dyspepsia (FD) is a syndrome in which several causes are probably involved. Our aim was to investigate the association between specific dyspeptic symptoms and Helicobacter pylori infection or delayed gastric emptying. METHODS: Nine hundred thirty-five consecutive outpatients with unexplained dyspepsia were studied. After appropriate investigation, 304 patients were diagnosed as affected by chronic FD and were tested for H. pylori infection and gastric emptying of solids by means of 13C-urea and 13C-octanoic acid breath tests. Four dyspeptic symptoms (epigastric pain or burning, postprandial fullness, nausea, and vomiting) were scored as absent, mild, moderate, or severe (0-3) according to their influence on the patients' activities. Symptoms of irritable bowel syndrome and gastroesophageal reflux disease were also assessed. On the basis of symptom scores, three groups were identified: "prevalent pain" (10.5%), "prevalent discomfort" (32.6 %), and "unclassifiable" dyspepsia (56.9%). RESULTS: Of the 304 patients with FD, 208 (68.4 %) were H. pylori-positive on urea breath test. Gastric emptying was delayed in 99 subjects (32.6%). Patients with "prevalent pain" were infected significantly more often (81.2% vs 59.6%; p = 0.026) and less frequently had delayed gastric emptying (6.2% vs 40.4%; p = 0.0001) than those with "prevalent discomfort." H. pylori infection was independently associated with age > or =40 yr and epigastric pain or burning > or =2 (odds ratio [OR] and 95% confidence interval [CI] 4.09 [2.39-7.00] and 1.70 [1.04-2.77], respectively). Delayed gastric emptying was independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (OR [95% CI]: 3.13 [1.06-9.18]). H. pylori status had no influence on gastric emptying. Logistic regression analysis showed that delayed gastric emptying, female sex, and concomitant symptoms of inflammatory bowel syndrome were independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (p = 0.0281, p = 0.0387, and p = 0.0316, respectively). Moreover, concomitant symptoms of gastroesophageal reflux disease, female sex, and H. pylori infection were independently associated with epigastric pain or burning > or =2 (p = 0.002, p = 0.0001, and p = 0.0875, respectively). CONCLUSIONS: Two subsets of FD patients have been identified on the basis of symptoms. One subgroup is mainly characterized by "prevalent pain," H. pylori infection, and normal gastric emptying; the other one demonstrates "prevalent discomfort" and delayed gastric emptying. These findings shed some light on possible etiopathogenetic mechanisms of FD.
OBJECTIVE: Uncontrolled, retrospective clinical studies have recently claimed that HCV infection could trigger the onset of diabetes mellitus (DM). We sought to verify the association between DM and liver diseases of different etiology, stage, and severity in a prospective study including gender- and age-matched controls. METHODS: Two hundred forty-seven patients with liver cirrhosis (184 men, 116 with an associated hepatocellular carcinoma, 34% in Child-Pugh's class A) were evaluated (group 1). One hundred fifty-seven (63.5) of them were HCV positive, 38 (15.5%) HBV positive, 49 (19.8%) alcohol abusers, and three (1.2%) cryptogenic. Two control groups were also included. The first control group consisted of 138 patients with chronic hepatitis due to HCV infection (73.9%), HBV infection (15.9%), or alcohol abuse (10.2%) (group 2). The second control group included 494 patients with an acute osteoarticular trauma, age- and gender-matched with patients in group 1 (group 3). RESULTS: Diabetes mellitus was present in 32.3%, 3.6%, and 9.7% of patients in groups 1, 2, and 3, respectively. When compared with controls (group 3), DM was significantly less frequent in group 2 (p < 0.004) and significantly more frequent in group 1 (p < 0.0001). The prevalence of DM was not different among patients with HCV, HBV infection, or alcohol abuse. In group 3, the prevalence of DM appeared to increase steadily with age. On the contrary, in patients with liver cirrhosis (group 1) DM was detected in about 20-30% of cases in all decades of age. In group 2, diabetics were found only in the 7th and 8th decades of life. At multivariate analysis cirrhosis and age were the only two factors independently associated with DM; odds ratios were 12.5 (95% confidence interval [C.I.], 6.74-20.4) for cirrhosis, and 1.47 for age (95% C.I. 0.39-2.55). CONCLUSIONS: Our findings disprove HCV infection as a trigger factor for DM, which should not be listed among the various extrahepatic manifestations of this viral infection.
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Although several papers on the urea breath test have been published, some methodological questions are still unsolved: the dose of 13C-urea, the test meal composition, the breath sampling, the fasting or fed condition, the postural settings, and the cut-off points. Moreover, special conditions, such as those occurring in paediatric and uraemic patients or subjects with previous gastric surgery should be borne in mind when evaluating the 13C-urea breath test results. This review focuses on methodological problems and potential pitfalls which can affect the accuracy of the 13C-urea breath test.
Splenic abscess is a rare disease whose diagnosis is difficult, though the use of modern imaging methods has increased diagnosed cases in recent years. We report a case of splenic abscess whose aetiology is unusual, namely, a gastric ulcer penetrating into the splenic artery and causing arterial thrombosis and septic embolism. Ultrasonography and ultrasound-guided puncture resolved any diagnostic doubt, and subsequent surgery confirmed the diagnosis. Pathogenesis, clinical picture, diagnostic methods, and treatment are discussed with reference to the literature.
BACKGROUND: Several genetic and subclinical markers have been associated with ulcerative colitis. AIM: To determine whether a significant association with HLA class I and II antigens was present in Italian ulcerative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies. METHODS: HLA class I and II antigens were studied by serological typing techniques and related to the presence of anti-neutrophil cytoplasmatic antibodies detected by means of indirect immunofluorescence. RESULTS: Patients with ulcerative colitis (n = 45) had a significantly increased frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5 (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy controls (n = 252 for HLA class I and 173 for HLA class II). No significant difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252 controls (p < 0.001). After stratifying ulcerative colitis patients according to their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p = 0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones. CONCLUSIONS: We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subclinical marker (anti-neutrophil cytoplasmatic antibodies) which seems to be genetically determined as shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies +ve ulcerative colitis.
Dyspepsia is a major public problem. It occurs in 25-40% of the general population negatively affecting the quality of life. 2-3% of the patients visited by the GP and up to 30% of those visited by the gastroenterologist have dyspepsia. Both diagnostic procedure and therapy are expensive. Definition, aetiology and pathogenesis of the disorder are not clear cut. The aim of this review is to outline the main trends in the relevant area of the clinical practice. The authors choose the most comprehensive definition among the thirty of the medical literature. To rule out, the most commonly and frequently wrong opinions risk factors have been examined. The authors distinguished between symptoms of function and organic dyspepsia and those of Irritable Bowel Syndrome and Gastro-Esophageal Reflux Disease, which often overlap and make difficult the management of the patient. The aetiology and pathogenesis have also been discussed, with particular emphasis on Hp. Advantages and drawbacks of different diagnostic approaches have been investigated. An age and symptoms related approach of the cases with dyspepsia is proposed, which allows to manage the patient without the necessity of invasive procedures. It is finally suggested that are cases which can be managed by the GP and others for whom the gastroenterologist intervention is mandatory.
AIMS: This study was carried out to evaluate whether the 13C-urea breath test could assess the intragastric Helicobacter pylori load and predict the outcome of infected subjects undergoing short-term triple therapy. METHODS: A total of 108 infected patients underwent upper endoscopy with antral biopsies and histological grading of Helicobacter pylori density. These patients received omeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d., and amoxycillin 1000 mg b.i.d. or tinidazole 500 mg b.i.d. for one week. 13C-urea breath test (75 mg 13C-urea; results expressed as Delta Over Baseline values at 30') was performed before and after therapy. According to pre-treatment Delta Over Baseline at 30' values, patients were assigned to low (< 16/1000), intermediate (16-35/1000) and high (> 35/1000) Delta Over Baseline at 30' groups. RESULTS: A significant correlation was found between pre-treatment Delta Over Baseline at 30' values and the density of Helicobacter pylori (rs = 0.76). The eradication rates were 82%, 67%, and 17% in the low, intermediate, and high Delta Over Baseline at 30' groups, respectively (p = 0.0001). When classified according to the outcome of therapy, the median pre-treatment Delta Over Baseline at 30' value was 15.7 in eradicated subjects vs 21.6 in non eradicated patients (p = 0.002). In patients who failed eradication, a significant difference was also observed between pre- and post-treatment Delta Over Baseline at 30' values (21.6 vs 15.6, p = 0.019). CONCLUSIONS: The 13C-urea breath test can be used to evaluate the intragastric bacterial load and to predict the outcome of standard eradication treatment.
Non-invasive evaluation of gastric emptying is generally performed by scintigraphy which is, however, not always applicable and is not suitable for children and child-bearing women. Recently, a new method based on stable isotope breath testing has been introduced in clinical practice i.e., the 13C-octanoic acid breath test. An overview is made here of the current knowledge on this technique with special emphasis on the principle of the test, the mathematics used to analyse the results, and the physiological, pathological, and pharmacological aspects of gastric emptying studied with this new method. Possible pitfalls of the test are also reported.
The sera of 46 Italian patients with chronic hepatitis delta virus (HDV) infection were analyzed for HDV RNA by polymerase chain reaction (PCR) amplification. Genetic analysis of sequences amplified from two regions of the HDV genome indicated that all HDV RNA-positive patients (98%) were infected with HDV genotype I. In Italy, infection with this genotype appeared to be associated with a broad spectrum of chronic disease. No subtypes of HDV genotype I were identified, nor were genetic variations clearly associated with different disease patterns; however, clustering of some sequences suggested correlations with geography and transmission route. Italian HDV genotype I sequences were more diverse than those from east Asia and North America, suggesting that HDV genotype I was likely introduced to Italy earlier and/or from multiple sources as compared to those areas. All sequences analyzed were predicted to fold into the unbranched rod structure typical of HDV RNA. Within this structure, three conserved features were identified, including sequences around the RNA editing site and the polyadenylation signal site. We conclude that in Italy, where HDV infection has been endemic, the overwhelmingly predominant genotype of HDV is genotype I.