Scientific theories and reality in gastric pathology.
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Animals↗
Biomedical subjects
G Budillon
Publications and source records attributed to G Budillon.
Coeliac disease and unfavourable outcome of pregnancy.
BACKGROUND: Up to 50% of women with untreated coeliac disease experience miscarriage or an unfavourable outcome of pregnancy. In most cases, after 6-12 months of a gluten free diet, no excess of unfavourable outcome of pregnancy is observed. The prevalence of undiagnosed coeliac disease among pregnant women is not known. AIM: To determine the prevalence of untreated coeliac disease among women attending the obstetrics-gynaecological department. METHODS: Endomysial antibodies, which are specific and sensitive for coeliac disease, were evaluated in all women attending the obstetrics-gynaecology department of a large city hospital over a 90 day period. RESULTS: Of 845 pregnant women screened, 12 were identified as having coeliac disease. Three had previously been diagnosed but were not following a gluten free diet. The remaining nine underwent a small intestinal biopsy, which confirmed the diagnosis. The outcome of pregnancy was unfavourable in seven of these 12 women. Six healthy babies were born with no problems after the women had been on a gluten free diet for one year. CONCLUSIONS: Overall, 1 in 70 women was affected by coeliac disease, either not diagnosed (nine cases) or not treated (three cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for coeliac disease should be included in the battery of tests prescribed for pregnant women. Coeliac disease is considerably more common than most of the diseases for which pregnant women are routinely screened. Unfavourable events associated with coeliac disease may be prevented by a gluten free diet.
Abortion, Spontaneous↗
Quantitative analysis of aldolase A mRNA in liver discriminates between hepatocellular carcinoma and cirrhosis.
BACKGROUND: Chronic liver diseases can progress to cirrhosis and to hepatocellular carcinoma. Timely and unequivocal recognition of the neoplastic evolution of cirrhosis is critical. To this aim, we used a noncompetitive reverse transcription-PCR procedure to analyze aldolase A mRNA in liver tissue from patients with chronic liver diseases at different stages. METHODS: We studied 12 patients with hepatocellular carcinoma, 19 patients affected by chronic hepatitis C or cirrhosis, and 7 healthy controls. Aldolase A mRNA was reverse-transcribed to cDNA, which was then amplified by PCR. The amplified segments were "read" with a novel dot-blot procedure. A calibrator with the same sequence, synthesized in vitro using a T7 phage promoter, was processed at scalar dilutions in parallel to the target samples to generate a calibration curve and so quantify the target mRNA (detection limit, 0.03 amol; linearity spanning five orders of magnitude). RESULTS: Aldolase A mRNA was approximately 10-fold higher in liver biopsies from patients with hepatocellular carcinoma vs patients with chronic hepatitis C or cirrhosis, and healthy individuals. Furthermore, aldolase A mRNA concentrations were 1.2- to 21.3-fold higher in 12 liver biopsies compared with the paired surrounding cirrhotic tissue. CONCLUSIONS: The quantitative analysis of liver tissue aldolase A mRNA differentiates between nonneoplastic chronic liver diseases and hepatocellular carcinoma, which suggests that it has diagnostic potential.
Carcinoma, Hepatocellular↗
Cryptic epitopes on alpha-fetoprotein induce spontaneous immune responses in hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis patients.
To determine alpha-fetoprotein (AFP) immunogenicity in vivo, the presence of antibodies in sera of 60 hepatocellular carcinoma, 15 liver cirrhosis, and 15 chronic hepatitis patients was evaluated by Western blotting and immunoprecipitation analyses using purified human AFP. High titers of anti-AFP immunoglobulins were detected in 14 hepatocellular carcinomas (P = 0.0006), 3 liver cirrhosis (P = 0.0173), and 1 chronic hepatitis patient, but they were not detected in 40 healthy individuals. Therefore, spontaneous immune responses to AFP are significantly associated to liver diseases (P = 0.0015). Patient immunoglobulins recognized proteic linear epitopes that were cryptic in the native protein, as demonstrated by their restricted reactivity with denatured deglycosylated AFP. Thus, in pathological liver conditions, tolerance to this self-molecule is circumvented. The identification of AFP immunogenic epitopes may contribute to defining novel immunotherapeutic strategies targeting this antigen.
Adult↗
Manometric study of hiatal hernia and its correlation with esophageal peristalsis.
The pathogenesis of gastroesophageal reflux disease (GERD) is considered multifactorial, but alterations of the esophagogastric junction (EGJ) and hiatal hernia play a prominent role. The correlations between hiatal hernia and the other pathogenetic factors are as yet unclear, and they need to be investigated by a methodological approach based on new anatomic and functional criteria. Our aim was to study, by stationary manometry, the relationships between small reducible hiatal hernia, identified by endoscopy, and esophageal peristalsis, in patients with and without GERD. According to the absence or presence of esophagitis (E), and the absence or presence of hiatal hernia (H), 58 subjects were divided into four groups: controls 10; H 14; E 10; and HE 24. Stationary manometry was performed by the rapid pull-through (RPT) technique, with catheter water perfused, to study the lower esophageal high pressure zone [lower esophageal sphincter (LES) and diaphragmatic crura] and the parameters of esophageal peristalsis. In patients with hiatal hernia, the various combinations of peak and/or deflection of manometric line pressure identified five EGJ profiles, only one of which reveals (by one-peak profile due to superimposed LES and diaphragmatic crura) the reducibility of the hernia. The frequency of the five profiles was calculated in the HE and H groups: a two-peak profile was significantly more prevalent in these patients, although less so in the group with esophagitis. In E patients the distal amplitude and the distal propagation of esophageal waves were significantly lower than in the other three groups (P < 0.05 vs controls and group HE; P < 0.01 vs group H). Furthermore, the distal amplitude was significantly higher in the group H than in the HE (P < 0.01). Our results show a better definition of hiatal hernia morphology, via the RPT technique, disclosing five pressure profiles. In addition, a significant link was found between small reducible hiatal hernia without GERD and wave amplitude of the distal esophagus. The amplification of peristaltic clearing may be considered the initial protective process against acid reflux; the breakdown of this mechanism may trigger the pathological sequence of GERD.
Adult↗
The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract.
BACKGROUND: The treatment of angiodysplasia and watermelon stomach, vascular abnormalities implicated in gastrointestinal bleeding of obscure origin, is a major clinical problem. AIM: To determine the efficacy of octreotide in patients with long-standing gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, resistant to previous treatments and not suitable for surgery because of old age and/or concomitant disorders. PATIENTS AND METHODS: We treated 17 patients (seven had isolated angiodysplasia, seven had multiple upper and lower gastrointestinal angiodysplasia, and three had watermelon stomach) with octreotide (0. 1 mg subcutaneous t.d.s. for 6 months). Six of the patients had liver cirrhosis, one had Glanzmann-type platelet derangement, two had cardiovascular diseases and one had chronic uraemia. RESULTS: Octreotide treatment stopped bleeding in 10 patients. A transient improvement was observed in four, who needed subsequent cyclical retreatment to correct low haemoglobin levels. No effect was observed in three, probably due to the severity of the concomitant disorders. CONCLUSIONS: Octreotide is a safe drug that may be useful to control the recurrent gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, especially in patients who are not candidates for surgery due to old age and/or concomitant disorders.
Adult↗
Performance characteristics of an enzyme-linked immunosorbent assay for determining salivary immunoglobulin G response to Helicobacter pylori.
We evaluated the salivary immunoglobulin G (IgG) immune response to Helicobacter pylori in 70 subjects by enzyme-linked immunosorbent assay (ELISA). Subjects with a positive H. pylori culture showed significantly higher titers of antibodies than subjects with no detectable H. pylori: the overall sensitivity and specificity of the test were 84 and 90%, respectively. The detection of salivary anti-H. pylori IgG antibodies may be considered as an alternative to serum IgG detection for ease of sample collection or when blood samples are not available in screening of patients with dyspepsia.
Antibodies, Bacterial↗
Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis.
BACKGROUND: Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability. AIM: To evaluate the effect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression. METHODS/SUBJECTS: Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients with H pylori negative chronic gastritis, 53 with H pylori positive chronic gastritis, and 11 with gastric cancer. RESULTS: All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pylori infection. Atrophy was present in three of 10 patients with H pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients with H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whom H pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged. CONCLUSIONS: Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication of H pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability.
Adult↗
Does Helicobacter pylori play a role in inflammatory bowel disease?
The cause of inflammatory bowel disease is still unknown although several bacterial and viral agents have been implicated in their aetiologies. Helicobacter pylori infection, the main cause of gastroduodenal diseases, could, theoretically, be involved in the pathogenesis of inflammatory bowel disease. In fact, it induces permeability alterations and immunological derangements in the stomach similar to those detected in the colon of inflammatory bowel disease patients. However, epidemiological data do not support this hypothesis and recent evidence even points to a low prevalence of Helicobacter pylori in inflammatory bowel disease. These data are discussed in the light of possible confounding factors.
Adult↗
Effect of N-acetyl-cysteine on lymphomonocyte glutathione and response to interferon treatment in C-virus chronic hepatitis.
BACKGROUND/AIM: Much controversy exists concerning effect of N-acetyl-cysteine, a precursor of glutathione, on the response to interferon treatment in patients with C-virus chronic hepatitis. The aim of this study was to evaluate the efficacy of interferon therapy with and without oral N-acetyl-cysteine. We also measured glutathione concentrations in lymphomonocytes of 25 patients with chronic C-virus hepatitis before and after interferon treatment and correlated the results with treatment response. METHODS: Glutathione was extracted from lymphomonocytes and measured with a modified high performance liquid chromatographic method in the 25 hepatitis patients and 12 healthy controls. RESULTS/CONCLUSIONS: 1) Hepatitis patients and controls had similar basal concentrations of lymphomonocytic glutathione; 2) neither interferon nor N-acetyl-cysteine significantly affected glutathione concentrations in patients; and 3) N-acetyl-cysteine did not affect response to interferon.
Acetylcysteine↗
Pathogenic properties of Helicobacter pylori.
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Gastric Mucosa↗
Activation of fetal promoters of insulinlike growth factors II gene in hepatitis C virus-related chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
Increased prevalence of hepatitis C virus (HCV) infection has been found in patients with hepatocellular carcinoma (HCC). The expression of insulinlike growth factor II (IGF-II) has been linked to hepatocarcinogenesis in the experimental animal and in humans. Since reactivation of fetal IGF-II transcripts has been observed in human HCC, we have analyzed the levels of adult P1 and fetal P3 and P4 IGF-II promoter-derived transcripts in the liver of patients with HCV-related chronic active hepatitis (CAH), cirrhosis, and HCC by means of a semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) assay. Transcripts derived from adult P1 promoter were increasingly expressed from normals to patients with CAH and cirrhosis, but were undetectable in the tumorous area of 5 of 7 HCC patients and present at low levels in the nontumorous area of all HCC patients. Transcripts derived from fetal P3 promoter were not detectable in normal subjects, while they were expressed abundantly in most CAH and all cirrhotic patients. Transcripts from fetal P4 promoter were detected at high levels in 3 of 9 CAH patients and in the majority of cirrhotic patients. Increased expression of fetal promoter-derived transcripts was also found in the liver of HCC patients, although levels were lower than in cirrhosis. Also, the activity of fetal P3 and P4 promoters was higher in the nontumorous than in the tumorous area of the liver of HCC patients. The expression of IGF-II transcripts was correlated with the rate of cell mitotic activity by measuring the expression of the proliferating cell nuclear antigen (PCNA) gene. PCNA messenger RNA (mRNA) levels progressively increased from normals to CAH and to cirrhotic patients, and persisted at a high level in the tumorous and in the nontumorous area of HCC subjects, thus showing that the increase of IGF-II transcripts in CAH and cirrhosis is accompanied by an activation of cell mitosis in these samples. These data suggest that the activation of IGF-II gene expression from adult and fetal promoters may play a role in premalignant proliferation observed in HCV-related chronic liver disease.
Adult↗
Prognostic value of the galactose test in predicting survival of patients with cirrhosis evaluated for liver transplantation. A prospective multicenter Italian study. AISF Group for the Study of Liver Transplantation. Associazione Italiana per lo Studio del Fegato.
AIMS/METHODS: The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis, belonging to Child class B and C, for 2 years each. RESULTS: The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p = 0.005), creatinine (p < 0.001), varices (p = 0.001) and galactose elimination capacity (p < 0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the end-point was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival. CONCLUSIONS: The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.
Adolescent↗
Intravenous load of fructose and fructose 1,6-diphosphate: effects on uricemia in patients with nonalcoholic liver disease.
OBJECTIVES: The i.v. load of fructose causes a significantly higher adenosine triphosphate (ATP) degradation and uric acid production in cirrhotic patients than in healthy controls. Resynthesis of ATP from adenosine diphosphate (ADP) may be facilitated by the phosphorylated compound fructose 1,6-diphosphate, which is used as energy support in parenteral nutrition. The aim of our research was to evaluate: 1) The 1-h uricemic effect of i.v. fructose (0.5 g/kg body weight) in 10 healthy controls and in 78 patients with differenct stages of non-alcoholic chronic liver damage associated or not with malnutrition or hepatocellular carcinoma; and 2) the effect of fructose 1,6-diphosphate (5 g/50 ml) administered i.v. after fructose infusion on the induced uricemia in a subgroup of 13 patients with well compensated cirrhosis. RESULTS AND CONCLUSIONS: The increase of uricemia above the basal level after fructose infusion was significantly higher (p < 0.01) in cirrhotics (3 mg/dl) than in controls (1.2 mg/dl) and in patients with chronic hepatitis (1.9 mg/dl) and was completely reversed by fructose 1,6-diphosphate in the patients tested. Neither Child-Pugh classes of cirrhosis nor malnutrition (present in about 50% of the patients) or hepatocarcinoma significantly affected the fructose-induced uricemia. Therefore, the fructose test efficiently differentiates cirrhotics from chronic hepatitis patients and healthy subjects, but it does not distinguish the various stages of the progression of cirrhosis or its complications.
Adult↗
Differential diagnosis between hepatocellular carcinoma and cirrhosis through a discriminant function based on results for serum analytes.
We applied a multivariate analysis to a large series of serum biochemical tests in an attempt to identify a function that could efficiently discriminate cirrhosis from hepatocellular carcinoma (HC). We analyzed two successive temporal cohorts (1987-90; 1991-94) of HC and cirrhotic patients, all histologically classified (first cohort: 69 cirrhosis and 39 HC; second cohort: 66 cirrhosis and 38 HC). Using data from the first temporal cohort of patients, we obtained a discriminant function based on seven serum analytes: alpha-fetoprotein, the hepatic isoenzyme of alkaline phosphatase, lactate dehydrogenase isoenzyme 5, total gamma-glutamyltransferase (GGT), GGT isoforms complexed with low-density lipoprotein, aspartate aminotransferase, and copper. The same panel of analytes emerged when the second cohort was tested and also when both cohorts were tested together. In the two successive cohorts (total, 212 patients) with a prevalence of cirrhosis vs HC of approximately 2:1, the discriminant function correctly classified 93% of cases, the highest percentage of correct classification of the two diseases obtained so far by laboratory approaches. Validation with the jackknife reallocation statistical algorithm confirmed these results. In addition, of six patients with liver cirrhosis for whom we had the opportunity of following up and observing the evolution to HC, five were classified as HC at diagnosis by the multivariate discriminant analysis; i.e., discriminant analysis provided a diagnostic lead time of 6-12 months over histology. This discriminant function, based on easy-to-perform serum biochemical tests, may help solve a fundamental problem of differential diagnosis in the evolution of chronic liver diseases from cirrhosis to HC.
Alkaline Phosphatase↗
Gastric pathology by Helicobacter pylori: recent advances in physiopathology diagnosis and therapy. Naples, Italy, October 20, 1995.
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Animals↗
Ascitic pseudouridine discriminates between hepatocarcinoma-derived ascites and cirrhotic ascites.
Various biochemical indexes discriminate neoplastic from nonneoplastic ascites. However, within the latter group, the distinction between cirrhotic ascites and ascites caused by hepatocarcinoma (HC) is usually based on liver biopsy or cytology. HC-derived ascites is included in the group of nonneoplastic ascites because it is not associated with peritoneal spreading of neoplastic cells. In 54 cases of cirrhotic ascites and 17 cases of HC ascites, all histologically diagnosed, ascitic pseudouridine concentrations discriminated cirrhotic from HC ascites. For example, using the cutoff value of 4.25 mumol/L (obtained by ROC curve analysis) resulted in a diagnostic sensitivity of 88.2% and a diagnostic specificity of 90.8%. Moreover, in cirrhosis, the ascitic concentrations of pseudouridine were lower than serum concentrations, and the two sets of values were correlated; in HC, however, ascitic pseudouridine concentrations were higher than serum concentrations, and the two were unrelated. These findings strongly suggest that in cirrhotic patients ascitic pseudouridine derives from serum by diffusion, whereas in HC patients the mechanism appears to be more complex.
Aged↗
Nicotinamide methylation and hepatic energy reserve: a study by liver perfusion in vitro.
BACKGROUND/AIMS: The synthesis of pyridine nucleotides from nicotinamide requires adenosine triphosphate. In man when exogenous nicotinamide is poorly utilized in this synthesis, the excess follows a dissipative metabolic pathway and is excreted in urine as N-methylnicotinamide. In human cirrhosis N-methylnicotinamide serum levels are higher than normal, in basal condition and after nicotinamide oral load. The aim of this study was to verify N-methylnicotinamide production in relation to hepatic content of adenosine triphosphate during in vitro perfusion of rat liver, in normal conditions and after adenosine triphosphate depletion by metabolic stress. METHODS: "Stress" was obtained by pre-washing with saline for 15 min before the perfusion with nutritive medium. RESULTS: The adenosine triphosphate decrease in the stressed liver was 38% after pre-washing with saline and 80% at the end of nutritive perfusion. In control liver the corresponding decreases were 1% after pre-washing with nutritive medium and 65% at the end of perfusion with the same medium. The total nicotinamide adenine dinucleotide decreases were 44% and 56% in the stressed liver, and 19% and 52% in the control liver. The output levels of N-methylnicotinamide at 90 min of rat liver nutritive perfusion were 31.50 +/- 4.72 nmol/g for normal liver and 66.40 +/- 13.17 for stressed liver (p<0.001). Liver adenosine triphosphate was inversely related to N-methylnicotinamide production (r=0.93; p<0.001). CONCLUSIONS: These data suggest that nicotinamide methylation may be enhanced when there is hepatic adenosine triphosphate decrease and energy failure induced by hypoxia or metabolic stress, similar to that obtained in vitro by saline washing before perfusion with nutritive medium. This study shows that the evaluation of N-methylnicotinamide production in man (before and after nicotinamide load) might be useful to explore the energy state of diseased liver.
Adenosine Triphosphate↗