Serological tests to monitor treatment of Helicobacter pylori.
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Biomarkers↗
Biomedical subjects
M Plebani
Publications and source records attributed to M Plebani.
Theophylline inhibits late asthmatic reactions induced by toluene diisocyanate in sensitised subjects.
Toluene diisocyanate (TDI)-induced asthma is a frequent occupational airway disease. To determine whether a calibrated dosage of oral slow-release theophylline inhibits asthmatic reactions and the associated increase of airway responsiveness to methacholine induced by TDI, we examined six asthmatic subjects who developed a late or a dual asthmatic reaction after TDI inhalation challenge. We administered oral slow-release theophylline or placebo to each subject for 7 days according to a double-blind, randomized, cross-over study design. When the subjects received a placebo, TDI caused a late or a dual asthmatic reaction. When the subjects received theophylline. TDI caused significantly reduced late asthmatic reactions. Mean serum theophylline concentrations were within the therapeutic range. Theophylline neither modified the baseline airway responsiveness to methacholine, nor the increase of airway responsiveness to methacholine induced by TDI. These results suggest that slow-release theophylline may improve TDI-induced late asthmatic reactions, but it does not change the baseline airway responsiveness to methacholine and the increase of airway responsiveness to methacholine induced by TDI.
Administration, Inhalation↗
Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection.
Glutathione is one of the endogenous protective chemicals, like prostaglandins, in the gastric mucosa. Depletion of these agents aggravate the chemical- or stress-induced gastric erosions and ulcers. However, gastroprotection can be achieved even in the presence of low mucosal concentration of glutathione and prostaglandins, indicating the presence of other protective chemicals (e.g. polyamines, growth factors, neurotransmitters, steroids) in the stomach. Protein sulfhydryls were also implicated in the mechanism of action of gastroprotective drugs. We recently tested the hypothesis that cysteine proteases might be a target of gastroprotective and antiulcer agents, and decided to look for the presence of proteases and protease inhibitors (PI) in the gastric mucosa and juice. Protease activity and PI were measured with general substrates hemoglobin, azocasein and albumin at optimal pH (2.0, 5.6, 7.4) of aspartic, cysteine and serine proteases. Homogenates of glandular stomach mucosa and gastric juice from fasted rats were incubated in the presence or absence of specific inhibitors and gastroprotective SH alkylators such as NEM or iodoacetate. PI was measured after acid and heat inactivation of endogenous proteinases and addition of pepsin, cysteine proteinase papain, or trypsin. Our results indicate that of the proteases found in the stomach 98% was pepsin at pH 2.0, and up to 56% or 24% was SH-sensitive at pH 5.6 or 7.4, respectively. Intragastric administration of SH alkylators such as NEM or iodoacetate exerted a dose- and time-dependent gastroprotection against chemically induced acute erosions and ulcers. Thus, in addition to glutathione, proteinases and their specific endogenous inhibitors may also be involved in gastric mucosal injury and protection.
Animals↗
Measurement of tryptase in endoscopic gastroduodenal biopsies: distribution and relationship with ulcer disease.
Tryptase, a serine endoprotease, was determined in mucosal biopsies from fundus, corpus, antrum and corpus-fundus of the stomach and from the duodenum in 15 controls, 66 patients with duodenal ulcer, 22 with gastric ulcer and 9 with duodenitis. Intra- and inter-assay coefficients of variation ranged from 3.3% to 8.0% and from 3.5% to 8.6%, respectively. In controls, the highest values for tryptase were found in the fundus and progressively decreased in the corpus, antrum and duodenum. Analysis of variance of data from repeated measurements, performed in six subjects having multiple determinations, achieved statistical significance (F = 16.85, P less than 0.001). Data from the corpus-fundus area documented a significant difference among patient groups (F = 2.70, P less than 0.05). Patients with an active gastric ulcer had higher mean values when compared to controls and to patients with healed gastric ulcer. A similar trend was found in patients with active duodenal ulcer. Furthermore, corpus-fundus tryptase evaluated longitudinally in three patients with an active ulcer (point A) and after healing (point B), showed significant decrease from point A to point B. By contrast it remained elevated or showed only minor decrease in two patients with a persistent active ulcer.
Adult↗
Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis.
This study was performed to investigate modifications in the serum bilirubin forms, hepatobiliary enzymes, and some glycoproteic substances in patients during the course of extrahepatic cholestasis (stage A) and following its clinical resolution (stage B). The series consisted of 16 patients: 11 had main bile duct stones; two, benign stenosis of the main bile duct; and three, main bile duct cancer. Cholestasis resolved spontaneously in one case, under endoscopy in two, and following surgery in 13. Five patients with liver cirrhosis and a picture of intrahepatic cholestasis following anesthesia were also investigated. Serum bilirubin forms were measured using van den Bergh's method and the alkaline methanolysis-HPLC procedure; the mono- and di-conjugated forms were considered together in the overall evaluation of the results. The hepatobiliary enzymes (ALP, GGT, and AST) were increased at stage A and significantly decreased at stage B. Similar patterns were observed in total (TB), unconjugated (UB), and conjugated bilirubin (CB) and in the percentage of CB out of TB (% CB). In the majority of patients, % CB at stage B was lower than at stage A, whereas in subjects with a high initial UB value, a different % CB pattern was observed. The direct bilirubin percentage (% DB), on the other hand, had a different pattern, and the variations between stages A and B were not significant. The pathophysiological bilirubin pattern was similar in patients with intrahepatic cholestasis. At stage A, in a number of patients the levels of glycoproteic substances (CA 19-9, TPA and ferritin) were raised, but at stage B they tended to decrease towards the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Acute reflux pancreatitis in rats: a comparison between two experimental models.
This study was undertaken in order to compare the reliability of two acute reflux pancreatitis models in rats, one performed by positioning a silicon tube in the duodenum and the other by creating a gastro-jejunal anastomosis. In two groups (A = 10 and B = 10 rats) a silicon tube was positioned in the duodenum; in the remaining two groups (C = 12 and D = 6 rats) a latero-lateral antecolic anisoperistaltic gastro-jejunal anastomosis was performed 30 days before surgery. A closed duodenal loop was created for 12 hours in groups A and C but not in B and D. Rats in both groups A and C developed acute pancreatic inflammation of a mild degree. Sham operated rats with silicon tube placement had higher histological damage scores than those with gastro-jejunal anastomosis. The difference found between the two groups of rats which underwent gastro-jejunal anastomosis was more marked than that between the two groups which had silicon tube placement. It was concluded that the creation of a gastro-jejunal anastomosis is probably the safer procedure to allow gastro-intestinal flow in acute reflux pancreatitis in rats.
Amylases↗
Urinary phospholipase A2 excretion in chronic pancreatic diseases.
This study was performed to investigate the behavior of phospholipase A2 (PLA2) in serum and urine of patients with chronic pancreatic diseases and to ascertain whether any factors influenced the results. In 30 controls, 45 patients with pancreatic cancer, 54 with chronic pancreatitis, and 64 with extrapancreatic diseases, serum and urinary PLA2, pancreatic isoamylase and RNase, and urinary N-acetylglucosaminidase (NAG) were measured. Serum PLA2 levels were higher in patients with chronic pancreatitis than in all the other groups. In our patients, only occasionally was urinary PLA2 elevated, the increase occurring almost exclusively in the presence of an acute inflammatory disease, e.g., relapsed chronic pancreatitis or active inflammatory bowel disease. A correlation was found between serum PLA2 and serum RNase, an indicator of tissue damage, but not between serum PLA2 and pancreatic isoamylase. Urinary PLA2 output was correlated with its renal input and with RNase output. No correlation was found between PLA2 output and pancreatic isoamylase or NAG urinary excretion. In conclusion, (1) the determination of serum PLA2 activity may be an aspecific test of pancreatic disease; (2) PLA2 urinary excretion occasionally increases, especially in the presence of severe phlogosis, which occurs in chronic pancreatitis, in particular during relapse; and (3) irrespective of the tissue origin of urinary PLA2, its increased excretion may be accounted for in part by its increased circulating levels. It is, however, more likely the consequence of a renal tubular dysfunction, which is sometimes found in patients with pancreatic diseases.
Adult↗
Role of serum fasting gastrin in screening for hypergastrinemic syndromes in duodenal ulcer disease.
Basal serum gastrin levels were measured in 237 patients with endoscopically confirmed duodenal ulcer and were higher than normal in 16 cases. Protein meal gastrin stimulation was performed on this group of 16 patients and on a control group of 48 patients with normal basal gastrin concentrations but high rates of either ulcer recurrence or of complications (e.g., bleeding or perforation); 21 patients from the two groups were also tested for serum gastrin inhibition with secretin. Four cases (25%) of antral G-cell hyperfunction were found in the first group, plus 1 case compatible with Zollinger-Ellison syndrome (6.2%). Only 1 case (2%) of antral G-cell hyperfunction was found among the 48 controls. These results suggest the clinical utility of routine basal gastrin measurement in screening for hypergastrinemic patients with duodenal ulcer disease.
Adult↗
Tumour markers in gastrointestinal malignancies: an update.
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Biomarkers, Tumor↗
Extra-hepatic cholestasis determines a reversible increase of glycoproteic tumour markers in benign and malignant diseases.
This study was performed in order to assess the relative role of cholestasis in increasing some serum glycoproteic markers of malignancy (CA 19-9, TPA, CEA). 30 Patients with benign and 16 with malignant extra-hepatic cholestasis were studied on admission (stage A) and after the operative or spontaneous resolution of the cholestatic picture (stage B). CA 19-9 and TPA were found to be lower in stage B than in stage A benign diseases. A similar behaviour was found in malignant diseases, although findings were significant only for CA 19-9. In neither of the patient groups was CEA found to present a significant trend. Extra-hepatic cholestasis appears able to increase per se serum glycoproteic markers in benign diseases, with variations proportional to the severity of the clinical picture. The same considerations can apply to malignancies, even if in these situations the production of tumour markers by the neoplastic growth should also be considered. We should therefore be cautious in assessing the diagnostic usefulness of new tumour markers when cholestasis is present.
Adult↗
Antigliadin antibody classes in chronic liver disease.
Antigliadin antibody (AGA) subtypes (IgG and IgA class) were tested in sera from 67 patients with chronic liver disease of different aetiology (29 with primary biliary cirrhosis (PBC), 31 with chronic non-A non-B hepatitis, and 7 with autoimmune chronic active hepatitis (CAH) compared with 23 subjects with inflammatory bowel disease (IBD). Nineteen patients with coeliac disease served as positive controls. IgA-AGA alone were found in 3.4% of patients with primary biliary cirrhosis and in 3.2% of non-A, non-B CAH. IgG-AGA alone were found in 1.3% of patients with IBD, in 6.8% of primary biliary cirrhosis and in 14.2% of autoimmune CAH. IgA-AGA and IgG-AGA together were found in 6.8% of PBC and in 1 patient with autoimmune CAH. Jejunal biopsy, performed in 7 out of the 2 patients with both IgA and IgG-AGA, showed the characteristic features of coeliac disease in one subject with autoimmune CAH. The same patient had the highest titre of AGA. In conclusion, these results indicate that AGA (either IgG and IgA) can be present at low titre in chronic liver disease and their presence may be secondary to the liver damage per sè. High titres of AGA in chronic liver disease may suggest a real association with coeliac disease.
Adult↗
Pathophysiology of the gastric microcirculation.
Mucosal blood flow performs an extremely important role in microcirculation wherein alterations necessarily lead to severe gastric and duodenal mucosal lesions. The removal of back-diffused H+ ions through the adaptation of microcirculatory flow represents a valid defence mechanism. The blood flow's inability to contain H+ back-diffusion lies at the bottom of rapid-onset acute mucosal lesions; moreover, it probably contributes to the onset of chronic ulcer in certain areas already precariously supplied, because of the breakdown of the mucosal barrier or a further reduction in blood supply. Portal hypertension leads to altered blood flow in the gastric microcirculation. This haemo-dynamic condition brings about a series of endoscopically evident changes which are probably a consequence of the conspicuous increase in mucosal and submucosal vascular area. This haemodynamic situation may be an aetiopatho-genetic factor in the cirrhotic subject's marked sensitivity to gastric mucosal damage.
Animals↗
The natural history of duodenal ulcer disease.
With a view to describing the natural history of duodenal ulcer, currently linked with powerful and widely used drugs, we retrospectively reviewed all patients followed-up at our unit between 1978 and 1989. All DU subjects with at least 5 years of clinical-endoscopic follow-up were admitted to the study. Concomitant gastric ulcer, previous gastrointestinal surgery and treatment other than with H2-blockers (where necessary) were considered exclusion criteria. Forty-four patients (35 males, 9 females, mean age 44.5) proved eligible for this study. At monthly intervals in the patients' history of ulcer disease (starting from a baseline month 0 when ulcer symptoms first appeared), we compared all cases in which the duration of disease coincided, i.e. for each month of the clinical course of the ulcer there was a certain number of patients at the same point in time; patients' histories coincided variously over a period ranging from 0 to 15 years. We considered endoscopically-diagnosed relapses (both symptomatic and asymptomatic) and hemorrhages as marker events for the activity of DU disease. A year-by-year duodenal ulcer activity rate was obtained for both treated and untreated subjects, as follows: No. of events/mean No. of patients followed-up per month x 100. Fisher's exact test and multivariate analysis (stepwise logistic regression) were used to investigate risk factors of poor outcome. We found that the years between the 1st and 5th and between the 10th and 15th from the onset of duodenal ulcer disease had higher peaks of activity, mostly in untreated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Comparison of two newly identified tumor markers (CAR-3 and DU-PAN-2) with CA 19-9 in patients with pancreatic cancer.
We compared the diagnostic utility of DU-PAN-2 and CAR-3 with that of CA 19-9 in differentiating pancreatic cancer (23 patients) from chronic pancreatitis (16 patients) and various extra-pancreatic diseases (28 patients) mainly of the upper gastrointestinal and biliary tract. The influence of some pathophysiologic variables on the three markers was also assessed. The sensitivities of the three markers in detecting pancreatic cancer were: CA 19-9, 83%; DU-PAN-2, 56%; and CAR-3, 39%. In patients with chronic pancreatitis and extra-pancreatic diseases, CA 19-9 gave the highest number of false positives. Receiver-operating characteristic curves showed that the ability of CAR-3 to discriminate between pancreatic cancer and other diseases was similar to that of CA 19-9, whereas DU-PAN-2 was a less reliable discriminator. Correlations were found between the behavior of all three markers and that of the cholestasis indices (ALP and GGT). Our findings indicate that DU-PAN-2 and CAR-3 serum determinations do not provide any more information than does CA 19-9 alone. The latter remains the marker of choice in the differential diagnosis of pancreatic cancer, even though it cannot be considered a definitive aid. Serum levels of all three markers increase in the presence of extra-hepatic cholestasis, possibly due to interference with the hepatic clearance of glycoproteins and destruction of ductal biliary epithelium.
Adult↗
CA 50 determination in body fluids: can we screen patients at risk for gastric cancer?
CA 50 (a tumor-associated gangliosidic antigen) levels have been determined by an RIA test in serum, gastric juice and urine of patients undergoing upper gastrointestinal tract endoscopy: 22 control subjects (no macroscopic or microscopic lesions), 29 patients with chronic atrophic gastritis, 20 with epithelial dysplasia and 16 with gastric cancer entered the study. Gastric juices were also tested for pH, protein concentration and specific gravity, urines for protein concentration and osmolarity. Serum and gastric juices were also tested for CEA levels and the results obtained with the two markers compared. In patients with gastric cancer, CA 50 gastric juice levels were statistically higher than in controls; a wide overlap was however present among groups, and sensitivity and specificity were respectively 38% and 85% for serum and 69% and 82% for gastric juice. Sensitivity and specificity were respectively 23% and 89% for CA 50 determination in urines. In this case, no statistically significant difference was observed between gastric cancer and control patients. A trend toward higher median values was observed in advanced with respect to early gastric cancer. A correlation was found between gastric juice and serum CA 50 levels, as well as between serum and urine levels of the marker. A correlation was also observed between CA 50 values and protein concentration in gastric juice and with osmolarity in urines. Overall, CA 50 levels were statistically higher in patients with intestinal metaplasia than in those who did not present the lesion. Increased CA 50 gastric juice levels are also observed in patients with chronic atrophic gastritis and epithelial dysplasia. CA 50 gastric juice and urine levels appear to be dependent, at least in part, on the concentration of the fluid.
Adult↗
Biochemical markers of hepatic fibrosis.
Most liver diseases lead to a pathobiochemical reaction termed liver fibrosis. This is a dynamic process implying different rates of progression or regression. Thus, histological examination of a liver biopsy is essential for a diagnosis but biochemical tests are necessary for assessing the activity of the process and monitoring its evolution. We review the most important constituents of liver connective tissue and the biochemical tests developed for evaluating liver fibrosis. The aminopeptide of type III procollagen is the most widely used parameter: two different radioimmunoassays have been developed with different affinities for the two circulating forms of the molecule. The determination of serum P3P reveals an elevation of blood levels both in acute and chronic liver diseases. In the first, serum P3P is an index of hepatic necrosis and inflammation which correlates with other biochemical parameters. In the second it is an index of active fibrogenesis. Moreover, in primary biliary cirrhosis this parameter is an independent prognostic variable and an important predictor of survival. Other immunoassays exist for different collagen cleavage products, but their clinical value is not established. Laminin and fibronectin are the principal structural glycoproteins in liver. Fibronectin determination does not seem to be of clinical value in liver disease. In contrast, serum laminin correlates with the severity of portal venous pressure in advanced liver disease. Its concentration parallels the severity of varices and may indicate the risk of bleeding. Hyaluronate is a high molecular weight polysaccharide, raised serum concentrations reflect both its increased synthesis by activated fibroblasts and its impaired catabolism by the liver. Thus, it may be useful for evaluating and monitoring the progression of chronic liver disease. The measurement of the activity of prolyl 4-hydroxylase as well as that of lysine oxidase and other enzymes has been proposed, but their clinical value is not sufficiently demonstrated. A panel of tests (e.g., laminin, hyaluronate and the aminopeptide of type III procollagen) seems to be recommended for a biochemical assessment of liver fibrosis in clinical practice.
Biomarkers↗
Precipitation method for separating and quantifying bone and liver alkaline phosphatase isoenzymes.
We evaluated a method for quantifying bone isoenzyme of alkaline phosphatase (ALP) which utilizes wheat-germ lectin to precipitate this fraction. In precision studies, CVs ranged from 3.2 to 11.4% (within-day) and from 3.7 to 11.5% (day-to-day). The assay procedure was linear to 1100 U/L and was easily adapted to automated kinetic measurement. Comparison of the precipitation method with an affinity electrophoretic method, which utilizes cellulose acetate as a support, demonstrated a satisfactory coefficient of correlation (r = 0.886). The reference range was determined in sera from 188 healthy adult subjects. The distribution of bone ALP values was also studied in 73 healthy children and in 30 healthy adolescents. To evaluate the clinical applicability of the method, the bone isoenzyme was determined in samples from several groups of subjects (pregnant women, patients with hepatobiliary diseases, patients with hepatocellular carcinoma without skeletal involvement, and patients with bone, liver or lymph node metastases). We found the method suitable for routine determination of bone alkaline phosphatase and for the screening of bone metastases. Because of its technical simplicity and satisfactory analytical performance, it can be used instead of the heat-inactivation procedure.
Adolescent↗
Urinary kallikrein excretion in chronic pancreatic diseases.
Variations in urinary kallikrein in pancreatic diseases were ascertained, and possible influencing factors were investigated. Serum amylase and urinary excretion of glandular kallikrein, pancreatic ribonuclease (RNase), gamma-glutamyltransferase (GGT) and amylase were measured in 24 control subjects, 39 patients with pancreatic cancer, 49 with pancreatitis and 63 with extra-pancreatic diseases. Urinary kallikrein was found to be elevated in a substantial number of patients with pancreatitis. Higher levels were detected in patients with a relapse, which was diagnosed using clinical and biochemical examinations. RNase was also increased in a high number of patients with pancreatic diseases, but was not correlated with pancreatic damage. In patients with pancreatitis, a correlation was found between urinary kallikrein and RNase excretions. No correlations were found between kallikrein and serum or urinary amylase and GGT. We can conclude that urinary kallikrein excretion increases in pancreatitis, especially when a phlogistic involvement of the pancreas is present; this condition may lead to a release of this ultrafiltrable enzyme in the circulation. Renal tubular damage, which determines a reduced reabsorption of this enzyme, seems to play a concomitant but minor role in this process.
Adult↗