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Biomedical subjects

R Clemente

Publications and source records attributed to R Clemente.

At least 19 recordsLinked to original sources

Differential redistribution of protein kinase C isoforms by cyclic AMP in HL60 cells.

In this study we have analyzed the distribution of protein kinase C isoforms in cytosol, membrane, and nucleus in HL60 cells. Furthermore, we have studied the redistribution of these isoforms after cyclic AMP treatment. Protein kinase C localization and cyclic AMP-induced translocation was demonstrated by Western blot analysis. Cytosol, membrane and nucleus in HL60 cells expressed the abundance of protein kinase C alpha, betaI, betaII, delta, lambda, and zeta isoforms. After cyclic AMP treatment, the amount of protein kinase C betaI and zeta increased only in the nucleus, while protein kinase C delta increased in the three fractions tested. These effects were dependent on the cyclic AMP concentration and duration of action. Our results suggest the existence of cross-talk between the cyclic AMP system and protein kinase C in HL60 cells. Taking into account the processes regulated by protein kinase C, these findings also suggest that cyclic AMP plays a regulatory role in various cellular responses in HL60 cells, such as differentiation and gene expression. The increase observed in PKC delta was due to cyclic AMP-dependent protein kinase C activation, and the synthesis of enzyme was probably activated by the nucleotide.

Biological Transport↗

Rifabutin-based 'rescue therapy' for Helicobacter pylori infected patients after failure of standard regimens.

BACKGROUND: The ideal treatment for patients who have failed eradication of Helicobacter pylori infection after standard proton pump inhibitor-based triple therapies has still to be determined. Although either a second course of triple therapy or a quadruple therapy (proton pump inhibitor plus bismuth-based triple therapy) has been proposed, the efficacy of these second-line therapies is relatively unknown. Therefore, alternative strategies are needed. AIM: To assess the efficacy and tolerability of rifabutin, a derivative of rifamycin-S, in patients who were still H. pylori infected after two or more courses of 1-week triple therapies. METHODS: Patients were given a 1-week regimen of pantoprazole 40 mg b.d. + amoxycillin 1 g b.d. + rifabutin 300 mg daily. Side-effects and compliance were determined at the end of therapy. Eradication rate was assessed with a 13C-urea breath test performed at 4 and 12 weeks after treatment. RESULTS: Forty-one patients (mean age 47 +/- 15 years) were studied. All patients took medications according to the proposed schedule. Side-effects were infrequent and mild. The eradication rates were 71% (95% CI: 57-85%) on intention-to-treat analysis and 74% (95% CI: 61-88%) on per protocol analysis. CONCLUSIONS: Rifabutin, in combination with pantoprazole and amoxycillin, is an effective and well tolerated regimen in patients who failed standard eradication treatments.

Adult↗

Fatal ulcerative panenteritis following colectomy in a patient with ulcerative colitis.

A 37-year-old man, previously submitted to colectomy for ulcerative pancolitis unresponsive to medical therapy, presented with nausea, vomiting, epigastric pain, and bloody diarrhea. An upper gastrointestinal endoscopy revealed mucosal friability, petechiae, and erosions throughout the duodenum, whereas prestomal ileum showed large ulcers and pseudopolyps. Histologically, a dense inflammation chiefly composed of lymphocytes and plasma cells with few neutrophils was detected. No bacteria, protozoa, and fungi could be detected. Despite intensive care, intra-1194 venous antibiotics and steroids, the patient died of diffuse intravascular coagulation and multiorgan failure. At post-mortem examination severe ulcerative lesions were observed scattered throughout the duodenum up to the distal ileum. The dramatic clinical presentation with fatal outcome, the widespread ulcers throughout the intestine, and the histological picture are peculiar features in our patient which can not be ascribed to any type of the ulcerative jejunoenteritis so far reported. Patients with pancolitis and diffuse ileal involvement do not necessarily have Crohn's disease but rather may have ulcerative colitis.

Adult↗

Serum tumour necrosis factor-alpha is increased in patients with Helicobacter pylori infection and CagA antibodies.

BACKGROUND: Helicobacter pylori causes gastric inflammation secondary to the mucosal release of cytokines and tumour necrosis factor-alpha. AIMS: To investigate whether serum levels of tumor necrosis factor-alpha correlate with Helicobacter pylori infection, CagA antibodies, 13C-urea breath test results, endoscopic, and histological findings. METHODS: Endoscopy (with gastric biopsies), 13C-urea breath test, and serological assay of CagA antibodies and tumour necrosis factor-alpha were performed in 172 dyspeptic patients. RESULTS: A total of 126 patients (73.2%) were infected; of the 126 patients, 84 with CagA antibodies (66.7%) showed a higher prevalence rate of duodenal ulcer (p = 0.03), more severe neutrophil infiltration (p = 0.03) and higher bacterial colonization (p = 0.03) than those without antibodies. CagA+ and CagA- groups differed also in 13C-urea breath test results (p = 0.03). A significant difference in serum tumour necrosis factor-alpha levels was observed between infected and uninfected individuals (p = 0.03) as well as between CagA+ and CagA- patients (p = 0.002). CONCLUSIONS: Helicobacter pylori infection is associated with increased serum levels of tumour necrosis factor-alpha. Subjects who harbour CagA positive strains have more severe mucosal damage, higher bacterial colonization, higher probability of developing duodenal ulcer and higher serum levels of tumour necrosis factor-alpha than those infected with CagA- strains.

Adult↗

Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of acute pancreatitis.

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.

Acute Disease↗

The 13C-urea breath test as a predictor of intragastric bacterial load and severity of Helicobacter pylori gastritis.

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.

Adult↗

Helicobacter pylori infection may undergo spontaneous eradication in children: a 2-year follow-up study.

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.

Adolescent↗

Intraduodenal lipase activity in celiac disease assessed by means of 13C mixed-triglyceride breath test.

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.

Adolescent↗

Patterns of symptoms in functional dyspepsia: role of Helicobacter pylori infection and delayed gastric emptying.

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.

Adult↗

Methodological problems and pitfalls of urea breath test.

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.

Adult↗

Relationship between the results of pre-treatment urea breath test and efficacy of eradication of Helicobacter pylori infection.

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.

Adult↗

13C-octanoic acid breath test: a reliable tool for measuring gastric emptying.

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.

Breath Tests↗

EC-IC bypass improves chronic ischemia in a patient with moyamoya disease secondary to sickle cell disease: an in vivo microdialysis study.

Patients with sickle cell disease may develop intracranial vascular disease, with the occlusion or obstruction of the large or small arteries, which may lead to the secondary development of moyamoya disease. In this report, we describe the neurochemical changes in the brain before, during, and after an extracranial-intracranial bypass procedure on a patient with sickle cell disease and a moyamoya disease like pattern on angiography. We used the in vivo microdialysis technique to measure the on-line pH, lactate and amino acid concentrations in the extracellular fluid. There were relatively high resting glutamate levels and a lower-than-normal pH in the extracellular fluid prior to the bypass, associated with chronic ischemia. During the bypass there was a short-lived increase in the glutamate levels. After revascularization, there was a rapid decrease in the glutamate levels and an increase in the pH value. The patient's preoperative neurological deficit improved post-operatively, corresponding to the biochemical changes towards normal values. These changes after revascularization suggest that chronic biochemical abnormalities due to brain ischemia may improve after cerebral revascularization.

Adult↗

Helicobacter pylori infection and growth delay in older children.

It is thought that Helicobacter pylori infection may influence growth rate in children. The aim of this study was to evaluate the prevalence of H pylori infection in healthy Italian children, and to look for differences in height between infected and non-infected subjects. Two hundred and sixteen children, aged 3 to 14 years, were tested for H pylori infection by 13C-urea breath test. Centile values for height were calculated. Composite indices for socioeconomic class and household crowding were also determined. Forty nine of 216 children (22.7%) were H pylori positive. The prevalence of infection increased with age. Eight of 49 H pylori positive children (16.3%) were below the 25th centile for height, compared with 13 of 167 H pylori negative children (7.8%). This difference became significant in children aged 8.5 to 14 years; in this group (n = 127), eight of 31 infected children (25.8%) were below the 25th centile for height, compared with eight of 96 non-infected children (8.3%). A significant correlation was found between socioeconomic conditions, household crowding, and H pylori status. By using stepwise logistic regression, only the centile value for height was significantly related to H pylori status in older children. Thus H pylori infection was associated with growth delay in older children, poor socioeconomic conditions, and household overcrowding. This finding is consistent with the hypothesis that H pylori infection is one of the environmental factors capable of affecting growth.

Adolescent↗

Hepatitis C virus infection and monoclonal gammopathies not associated with cryoglobulinemia.

A pathogenetic role of HCV has been recently postulated in some lymphoproliferative disorders and in particular in essential mixed cryoglobulinemia. To assess the relevance of HCV infection in multiple myeloma, Waldenström's macroglobulinemia and monoclonal gammopathy of undetermined significance in the absence of cryoglobulinemia (cryo-ve MG), 102 patients were evaluated for antiHCV, HCVRNA and HCV genotypes. A control group of 466 patients referring for acute trauma to the Orthopedic Division of our hospital was also studied. The overall prevalence of HCV was 15.6% in MG patients and 5.4% in the control group (P= < 0.001). Since only patients with MG older than 50 years had HCV infection, we compared the prevalence rate of infection in patients aged 50 and older: in cryo-ve MG HCV prevalence was 17.9%, while in patients with an acute trauma it was 10%; the difference was not statistically significant. In addition, occurrence of cryo-ve MG was investigated in 614 antiHCV+ patients with chronic liver disease and was found in 1.9%. Comparing all the 28 cryo-ve MG patients HCV+ with an appropriately matched control group of HCV+ patients without MG, no difference in severity of liver disease and genotype distribution was detected. These findings show that: (1) among cryo-ve MG, HCV infection is frequent as shown in the appropriately matched control population; (2) prevalence of cryo-ve MG in antiHCV patients with chronic liver disease is similar to the rate found in the general population; and (3) HCV infection and disease do not differ in patients with and without cryo-ve MG.

Adult↗