Screening for Helicobacter pylori.
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Biomedical subjects
Publications and source records attributed to M Miglioli.
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Sera from 30 patients with community-acquired, biopsy-proven chronic non-a,non-B hepatitis (NANBH) were tested for antibodies to the C100 protein of hepatitis C virus (HCV). The 20 patients who showed reactivity in this assay were followed prospectively for 6 months, during which time seven were treated with recombinant alpha-interferon. HCV RNA was detected by "nested" polymerase chain reaction (PCR) in 19 of the 20 anti-C100-positive sera taken at the onset of the study and also in five of the ten anti-C100-negative sera. Pretreatment viraemia levels ranged from 2 x 10(3) to 2 x 10(8) HCV genomes/ml. After 6 months of interferon, elevated serum alanine aminotransferase (ALT) levels had fallen to normal in four of the seven treated patients. In each case the response to interferon was accompanied by either a disappearance of or a decline (1 log to 8 log reduction) in viraemia. HCV genome titres in the three nonresponders and in the 13 untreated anti-C100-positive patients did not change significantly over this 6 month period. These findings confirm the aetiological role of HCV in community-acquired NANBH and suggest that quantitative PCR will become a valuable technique for monitoring the antiviral effect of interferon and other experimental treatments.
The in vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-ASA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2-.) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochrome c (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2-. generating systems, 5-ASA being the most powerful (greater than 50% of inhibition in the PMNs system and greater than 70% in the X/XOD system at 10 microM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.
The recent cloning of the genome of hepatitis C virus (HCV) has allowed the detection of antibodies to HCV (anti-HCV) in human serum. The presence of serum antibodies to HCV often indicates active infection with HCV. We have assessed the serological and histological features in a group of alcoholic patients with chronic liver disease and have evaluated the possible etiologic role of HCV infection in the development of liver damage. Serum samples and liver biopsy specimens were obtained from 41 consecutive patients, all having a definite history of alcohol abuse and evidence of chronic hypertransaminasemia. Fifteen patients (37%) were positive for anti-HCV by ELISA, and 13 (86.6%) of them were also positive by RIBA. Eleven of these patients had histologic features of chronic active hepatitis (CAH), a lesion which is not known to be induced by excessive alcohol intake. No other possible causes of CAH were found, and CAH was not present in any of the anti-HCV negative patients. In patients with CAH, mean AST to ALT ratio was less than 1 (0.6), a finding which is characteristic of viral rather than alcoholic chronic liver disease. In conclusion, our study suggests that sporadic hepatitis C virus infection plays an etiologic role in the development of chronic active liver disease in a subgroup of alcoholic patients.
The nutritional consequences of total colectomy and ileal pouch-anal anastomosis (IPAA) were assessed by evaluating 36 patients at the end of the defunctionalised stage (DS group) and 18 patients with recanalised IPAA (IPAA group). The changes in protein-calorie and zinc status occurring after the closure of the diverting ileostomy were evaluated also in 11 patients assessed both during the DS and the IPAA stage. The results were compared with those observed in 14 patients who underwent a Brooke-type permanent ileostomy (PI group). In the DS group there were protein-calorie malnutrition in 50% of cases characterised by body weight, TSF and AMC values lower than normal associated with normal serum protein levels; severe salt and water depletion with secondary aldosteronism in 90%; normal calcium-phosphorus balance in all but few cases, low values of parameters related to vitamin D and K, Fe, Zn and Cu status in 6-25% of cases and normal folate status. In the IPAA group all the anthropmetric parameters improved significantly after the closure of the protective ileostomy, but muscle mass (AMC) remained lower than normal in 40% of cases; mild salt depletion (urinary Na K ratio between 1 and 2) was observed in 1 3 of cases and of severe degree (urinary Na K < 1 ) in 20%; lower serum Zn occurred in 60% of patients probably due to greater requirements of the metal, secondary to increased muscle protein synthesis; parameters of calcium-phosphorus balance, vitamin D and K, folate, Fe and Cu status, were normal in almost all the cases. In the PI group, protein-calorie and salt and mineral nutritional status were similar to those of the IPAA group, whereas Zn status was normal in all the patients and erythrocytes folate levels and prothrombin time were significantly lower than in the IPAA group. These last two results might be explained by the different characteristics of the small bowel flora occurring in the two types of ileostomy.
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5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.
Although cell proliferation studies on gastric mucosa are relatively few compared to the results obtained in the large bowel, they brought important contributions to our knowledge of the mechanisms involved in the development and progression of neoplasia. In normal gastric mucosa, the proliferative zone is limited to the neck region of the glands. In diseases at risk for gastric cancer, such as chronic atrophic gastritis, two main features have been observed: an increased cell proliferation rate and expansion or upward displacement of the proliferative compartment. However, while a high cell turnover rate can be due to many stimuli such as inflammation or the effect of hormones (i. e. gastrin), the expansion of the proliferative compartment is more evident with the development and progression of neoplasia. It could be due to an error in the control of cell proliferation and maturation. This kinetic pattern is probably a marker of gastric cancer risk. Application of these observations in clinical investigations are the search for proliferative abnormalities and other phenotypical markers in order to define an individual profile of cancer risk, and to evaluate the effects of xenobiotics or dietary intervention in controlled trials.
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Constipation is commonly defined on the basis of the number of bowel movements in a week (greater than 3 week) or on the stool weight (less than 35 g/day) and on their consistency and expulsion capacity. A pathophysiological classification of constipation subdivides the patients into 2 groups. The first includes those patients in which a propulsion defect is prevalent (inertia coli) and the second one comprehends those in which a predominant expulsion defect is found. This second group consists of patients with myogenic, neurogenic or mechanical disorders. Moreover, we can consider in this group those patients with irritable bowel syndrome (IBS) who show a reduction of rectal compliance and those who produce "inappropriate stools". Finally, in this group we can find those patients having the so-called faecal impaction, that is an abnormality of either sensitivity or stimulus to defecate frequently observed in the elderly and in children.
Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis.
Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.
The relationship between intestinal permeability to an oral dose (100 mu Ci) of [51CR]EDTA and the inflammatory activity of Crohn's disease was studied in 63 adult patients (32 unresected and 31 resected) who underwent 162 evaluations. The results of the [51CR]EDTA test were compared with the serum levels of the acute-phase reactant proteins (APRP) and with the result of the [111In]leukocyte scanning, respectively, as an indirect and direct method to assess intestinal inflammation. In a group of healthy adult controls, the upper normal value for the 24-hr urinary [51CR]EDTA excretion was 3.61 (97.5% percentile) and the mean coefficient of variation was 21%. Sensitivity and specificity of the [51CR]EDTA test in identifying active inflammation expressed by increased serum levels of APRP were, respectively, 97% and 54% in the unresected group and 68% and 52% in the resected group of patients. The low specificity of the test was due to the presence of increased [51CR]EDTA urinary excretion in about half the cases with normal serum levels of APRP. The [111In]leukocyte scanning was performed in a subgroup of 11 patients (three unresected and eight resected) with normal serum levels of APRP, six with increased and five with normal [51CR]EDTA urinary excretion. All six patients with increased intestinal permeability had a positive 111In image of mild to moderate degree of activity. A positive 111In scan was present in two of the five patients with normal permeability; these were two resected patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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We evaluated the influence of age and sex on rectal cell proliferation of 69 hospital controls and 66 patients with colorectal adenomas, by means of incubation of rectal biopsies with tritiated thymidine and autoradiography. In particular, we evaluated the labeling frequency in the upper 40% of rectal crypts (0 h), actually considered as a reliable kinetic marker of colon cancer risk. A direct correlation between 0h and age was found in control subjects (P less than 0.02) but not in adenomas patients (P = NS). Moreover, control subjects over 65 years of age showed a shift of the proliferative compartment similar to that observed in the adenomas group. After adjusting for the age, we did not observe any significant effect of the sex of patients or controls on their cell kinetics parameters. Our results are in agreement with those previously reported on smaller series and with epidemiological studies which indicate a high risk for developing colorectal neoplasia in the elderly subjects.
We report two cases of pulmonary involvement in ulcerative colitis. The first patient, a 37-year-old woman, had bilateral basal bronchiectasis full of mucopurulent secretion, with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach. The second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection. In the second patient, a sulfasalazine reaction as an etiologic factor was excluded, while in the first this possibility seemed unlikely. Therefore, we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis.
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Clinical experience with mesalazine enemas in the treatment of ulcerative colitis is reviewed. After rectal administration, plasma mesalazine levels remain low, and 15% of the administered dose is recovered in the urine. Enemas containing 2 and 4 g of mesalazine have been shown to be effective, safe, and well tolerated by patients with mild and moderate ulcerative colitis. Patients who cannot tolerate sulfasalazine and patients who do not respond to other treatments have been successfully treated with mesalazine enemas. Suppositories of mesalazine are more suitable for patients with disease confined to the distal region of the colon, whereas mesalazine enemas should be used in patients with more extensive disease. Mesalazine enemas have also been used for maintenance therapy in ulcerative colitis.