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Biomedical subjects

Dario Conte

Publications and source records attributed to Dario Conte.

At least 19 recordsLinked to original sources

The role of ultrasonography in patients with celiac disease.

The aim of the present review was to summarize the current evidence on the role of ultrasonography (US) and doppler-US in the diagnosis of celiac disease. Several ultrasonographic signs have been reported in the association with celiac disease in studies using real-time US. Firstly, case control studies identified some of these US signs and then in a prospective series some of these parameters, due to their high specificity, have been shown to be of value in confirming CD diagnosis, whereas others, due to their high sensitivity, have been demonstrated to be useful in excluding the presence of the disease. The pattern of splanchnic circulation in CD have extensively been investigated by several studies all of which reported similar results and identified a hyperdynamic mesenteric circulation that reverts to normal values after successful a gluten-free regimen. The last part of this review will deal with the possible role of US in identifying the most severe and common intestinal complication of CD, i.e. the enteropathy-associated T cell non-Hodgkin lymphoma.

Abdomen↗

Iron regulatory proteins 1 and 2 in human monocytes, macrophages and duodenum: expression and regulation in hereditary hemochromatosis and iron deficiency.

BACKGROUND AND OBJECTIVES: The functions of the iron regulatory proteins (IRP1 and IRP2), which control cellular iron homeostasis are similar but not identical. As an inappropriate up-regulation of total IRP activity has been found in the duodenum and monocytes of patients with hereditary hemochromatosis (HH), we investigated the respective roles of IRP1 and IRP2 in these settings. DESIGN AND METHODS: Specific antibodies were used in RNA-supershift, immunoblotting and immunohistochemistry assays to evaluate IRP1 and IRP2 separately in monocytes, macrophages and duodenum of control subjects, and patients with HH or iron-deficiency anemia. RESULTS: The activity of both IRP1 and IRP2 and the levels of IRP2 were: (i) higher in monocytes and macrophages of HH patients than in those of control subjects; (ii) increased in the duodenal samples of the patients with HH and iron-deficiency anemia. IRP2 levels increased when monocytes differentiated to macrophages. Under all of the examined conditions, IRP2 was induced to a greater extent. In the duodenum of HH and anemic patients, IRP1 was shifted from the aconitase form (present in controls) to the apoform, whereas the IRP1 in monocytes/macrophages was always in the apoform, in both the patients and controls. The RNA-bound fraction of IRP1 was small in all of the samples. Both IRP were expressed more in the villi than in the crypts of the duodenum, with no differences in localization or expression between the patients and controls. INTERPRETATION AND CONCLUSIONS: These findings of the first extensive investigation of the comparative expression of the two IRP in human tissues and blood cells indicate that IRP2 is the major regulator of intracellular iron homeostasis in humans.

Adult↗

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease.

OBJECTIVE: A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. MATERIAL AND METHODS: Twelve patients (7 M, age range 24-65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25-54 years). RESULTS: In the patients' group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)+/-6 (SEM) versus 86+/-6 and 232 min+/-16 versus 160+/-7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): -22 min (mean); -10 to -34 (95% CI) and -48 min; -10 to -85, respectively, decreased both percentage of time at pH < 4 (p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R2<0.005). CONCLUSION: The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.

Adult↗

Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review.

BACKGROUND AND AIM: In patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing hepatocellular carcinoma (HCC) has never been systematically assessed, and present systematic review was aimed at this issue. METHODS: Pertinent cross-sectional studies having as a reference standard pathological examinations of the explanted liver or resected segment(s), biopsies of focal lesion(s), and/or a period of follow-up, were identified using MEDLINE, EMBASE, Cochrane Library, and CancerLit. Pooled sensitivity, specificity, and likelihood ratios (LR) were calculated using the random effect model. Summary receiver operating characteristic (SROC) curve and predefined subgroup analyses were made when indicated. RESULTS: The pooled estimates of the 14 US studies were 60% (95% CI 44-76) for sensitivity, 97% (95% CI 95-98) for specificity, 18 (95% CI 8-37) for LR+, and 0.5 (95% CI 0.4-0.6) for LR-; for the 10 CT studies sensitivity was 68% (95% CI 55-80), specificity 93% (95% CI 89-96), LR+ 6 (95% CI 3-12),and LR- 0.4 (95% CI 0.3-0.6); for the nine MRI studies sensitivity was 81% (95% CI 70-91), specificity 85% (95%CI 77-93), LR+ 3.9 (95%CI 2-7), and LR- 0.3 (95% CI 0.2-0.5). The sensitivity and specificity of AFP varied widely, and this could not be entirely attributed to the threshold effect of the different cutoff levels used. CONCLUSIONS: US is highly specific but insufficiently sensitive to detect HCC in many cirrhotics or to support an effective surveillance program. The operative characteristics of CT are comparable, whereas MRI is more sensitive. High-quality prospective studies are needed to define the actual diagnostic role of AFP.

Biomarkers, Tumor↗

Computer-assisted evaluation of perianal fistula activity by means of anal ultrasound in patients with Crohn's disease.

OBJECTIVES: Assessment of the activity of perianal fistulas may be of clinical relevance in patients with Crohn's disease. Fistula activity is currently evaluated by means of magnetic resonance imaging; anal ultrasound can also be used, but its diagnostic performance in this setting remains to be defined. Our aims were to evaluate the agreement between clinical examination, magnetic resonance imaging, and anal ultrasound in assessing perianal fistula activity, and to apply computerized analysis to improve the assessment of ultrasound images. METHODS: Thirty-one consecutive patients with Crohn's perianal fistulas underwent clinical examination, and magnetic resonance and anal ultrasound imaging. Active fistulas were defined as the presence of active drainage or signs of local inflammation on clinical examination, and the definition was confirmed by surgical examination. Activity was assessed on the basis of T2 hyperintensity on magnetic resonance imaging and the degree of hypoechogenicity on anal ultrasound; the anal ultrasound images were also analyzed using dedicated computer image-analysis software. RESULTS: Twenty-five patients had an active fistula at clinical examination. The agreement between clinical examination and magnetic resonance imaging was good (k-value = 0.739), whereas that with anal ultrasound was only fair (k-value = 0.266-0.294); computer-assisted analysis of the anal ultrasound images improved the agreement from fair to good (k-value = 0.608-0.670). CONCLUSIONS: Anal ultrasound can be used to assess fistula track activity in patients with Crohn's disease. The diagnostic performance of the technique can be improved to values comparable with those of magnetic resonance imaging by using a computer-assisted evaluation of the anal ultrasound images.

Adult↗

Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C.

AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%, the model defined four levels of post-test probability of severe fibrosis/cirrhosis: <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute). The predicted probabilities were compared with the observed patientso distribution according to the histology (METAVIR). RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%) or low (<10%) probability of severe fibrosis, 33% with a probability ranging from 75% to 90%, and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to 74%). The observed frequency of severe fibrosis/cirrhosis was within the predefined ranges. CONCLUSION: The model can correctly identify 67% of patients with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.

Alanine Transaminase↗

Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis.

A 35-year-old male with an 11-year history of intestinal pseudo-obstruction associated with an idiopathic inflammatory insult of the myenteric plexus and the presence of circulating anti-Hu antibodies developed a neurological syndrome characterized by bilateral hearing loss, deteriorating balance, an unsteady gait and difficulty in estimating distances. A similar neurological syndrome has previously been described in older patients among the paraneoplasic syndromes associated with small-cell lung carcinoma and the presence of circulating anti-Hu antibodies, but never in the rare cancer-free patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction. The patient underwent a steroid treatment. No further episodes of functional intestinal obstruction were observed and, after an initial improvement, the neurological symptoms stabilized, leaving a permanent reduction in hearing function and an unsteady gait. The case shows that an idiopathic inflammatory insult of the myenteric plexus may precede (and perhaps lead to) central nervous system impairment in patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction.

Adult↗

"Pseudotumoral" hepatic areas in acute alcoholic hepatitis: a computed tomography and histological study.

Computed tomography (CT) findings in acute alcoholic hepatitis (AAH) have not been investigated and a "pseudotumoral aspect" of the liver parenchyma has rarely been reported as an exceedingly unusual finding. We observed 11 patients with AAH over a 1-yr period, five of whom underwent CT for concomitant clinical reasons. Arterial enhancement indicated areas of hypervascularized tissue in all cases, and the histological findings were fully consistent with AAH without any sign of malignancy. The present findings suggest that the above pattern is not uncommon in AAH and should be carefully considered in order to avoid diagnostic errors.

Adult↗

Role of US in detection of Crohn disease: meta-analysis.

PURPOSE: To evaluate the accuracy of ultrasonography (US) in the detection of Crohn disease in adults by systematically reviewing both cohort studies (those including patients whose clinical characteristics were consistent with those caused by an inflammatory bowel disease) and case-control studies (those in which patients with Crohn disease were compared with patients with other bowel diseases or healthy control subjects). MATERIALS AND METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were used to retrieve all the cross-sectional studies that assessed the diagnostic accuracy of US against that of one of several predefined reference standards (ie, radiologic, endoscopic, or histologic findings). The studies that fulfilled the inclusion criteria were identified, and their methodological quality was evaluated. Of the 2860 primary studies identified, two case-control and five cohort series fulfilled the inclusion criteria. Statistical analysis was performed by using the summary receiver operating characteristic (SROC) model. RESULTS: The ranges of US sensitivity and specificity for the diagnosis of Crohn disease reported for the included series were 75%-94% and 67%-100%, respectively; the heterogeneity of these values prevented the calculation of a cumulative value. The SROC curve revealed a clear cutoff effect that depended on the chosen bowel wall thickness threshold. Sensitivity and specificity of 88% and 93%, respectively, were achieved when a bowel wall thickness threshold greater than 3 mm was used, and sensitivity and specificity of 75% and 97%, respectively, were achieved when a threshold greater than 4 mm was used. CONCLUSION: US examination seems appropriate for confirming or excluding Crohn disease as a diagnosis in a clinical context characterized by a pretest probability of Crohn disease that ranges from 12% to about 60%. In particular, for Crohn disease limited to the ileum, US may represent a valid alternative to the small-bowel series, while for colonic involvement US may be useful in ruling out the diagnosis.

Adult↗

Erythrocyte ferritin concentration: analytical performance of the immunoenzymatic IMx-Ferritin (Abbott) assay.

Together with serum ferritin, erythrocyte ferritincan be a valuable diagnostic tool for evaluating the degree of impaired iron metabolism in different diseases. We collected peripheral blood samples from 64 subjects (22 healthy volunteers, 20 patients with hereditary hemochromatosis, and 22 patients on regular hemodialysis with secondary anemia) to evaluate whether an immunoenzymatic method generally used for serum ferritin can also be used to determine erythrocyte ferritin levels under various conditions of body iron status. Serum and erythrocyte ferritin levels were assayed in parallel using a microparticle enzyme immunoassay (MEIA) IMx-Ferritin kit and an IMx analyzer. The inter-assay imprecision of the serum and erythrocyte ferritin assays was 4.9% and 5.05%, the intra-assay imprecision was 2.2% and 2.3%, and the mean recovery was 102% (range 96-105%) and 101% (range 99-105%), respectively. Both serum and erythrocyte ferritin assays showed a detection limit of 1 microg/L and good linearity (R(2) = 0.99) in the intervals 13.9-443 and 3.9-135.6 microg/L, respectively. Our findings demonstrate that the IMx-Ferritin assay currently used to measure serum ferritin levels can also be adopted to measure erythrocyte ferritin insofar as it clearly discriminates high and low erythrocyte ferritin levels in cases of both iron overload and deficiency.

Adult↗

Adaptive changes of duodenal iron transport proteins in celiac disease.

Iron deficiency is a manifestation of celiac disease (CD) usually attributed to a decreased absorptive surface, although no data on the regulation of iron transport under these conditions are currently available. Our aim was to evaluate divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), ferroportin 1 (FP1), hephaestin, and transferrin receptor 1 (TfR1) expression, as well as iron regulatory protein (IRP) activity in duodenal biopsies from control, anemic, and CD patients. We studied 10 subjects with dyspepsia, 6 with iron-deficiency anemia, and 25 with CD. mRNA levels were determined by real-time PCR, protein expression by Western blotting or immunohistochemistry, and IRP activity by gel shift assay. Our results showed that DMT1, FP1, hephaestin, and TfR1 mRNA levels were significantly increased in CD patients with reduced body iron stores compared with controls, similar to what was observed in anemic patients. Protein expression paralleled the mRNAs changes. DMT1 protein expression was localized in differentiated enterocytes at the villi tips in controls, whereas with iron deficiency it was observed throughout the villi. FP1 expression was localized on the basolateral membrane of enterocytes and increased with low iron stores. TfR1 was localized in the crypts in controls but also in the villi with iron deficiency. These changes were paralleled by IRP activity, which increased in all iron-deficient subjects. We conclude that duodenal DMT1, FP1, hephaestin, and TfR1 expression and IRP activity, thus the iron absorption capacity, are upregulated in CD patients as a consequence of iron deficiency, whereas the increased enterocyte proliferation observed in CD has no effect on iron uptake regulation.

Adaptation, Physiological↗

Accuracy of ultrasonography in predicting celiac disease.

BACKGROUND: Various ultrasonographic (US) signs have been reported in overt celiac disease (CD). The aim of this study was to investigate the diagnostic accuracy of 6 US parameters in predicting CD. METHODS: One hundred sixty-two consecutive patients with chronic diarrhea (n=105), iron deficiency anemia (n=25), or dyspepsia (n=32) underwent anti-endomysial IgA antibody determination and duodenal biopsy. Moreover, US evaluation of 6 parameters (ie, fasting gallbladder volume, transverse diameter of small bowel loops, thickness of the small bowel wall, pattern of peristalsis, presence of free abdominal fluid, and diameter of the mesenteric lymph nodes) was done by 2 operators blind to the serological and histological findings. The pretest probability of CD was estimated to be between 5% and 10%. The percentage of agreement between US and histologic findings, the sensitivity, specificity, positive and negative likelihood ratios, and the posttest probability for positive and negative results were calculated. RESULTS: Celiac disease was diagnosed in 12 patients (7.4%). An increased gallbladder volume, the presence of free fluid in the abdominal cavity, and enlarged mesenteric lymph nodes showed a specificity of 96%, 96%, and 97%, respectively (95% confidence intervals [CIs], 92%-99%, 93%-99%, and 95%-99%), whereas the presence of dilated small bowel loops with increased fluid content and increased peristalsis had a sensitivity of 92% and 83%, respectively (95% CIs, 76%-100% and 62%-100%). Eleven (92%) of the 12 patients with celiac disease and 35 (23%) of the 150 patients who did not have the disease had at least 1 US sign (P=.001); all of the US signs were concomitantly present in 4 patients with CD (33%) and 1 patient without CD (0.6%) (P=.001). CONCLUSION: Ultrasonographic evaluation can accurately predict CD but its place in the diagnostic algorithm depends upon the probability of the disease in the considered population.

Adolescent↗

Epstein-Barr virus-associated lymphoma in Crohn's disease.

Although no increased risk of developing lymphoproliferative disorders has been observed in population-based studies of patients with Crohn's disease, the possibility has been suggested in the subset of patients previously treated with thiopurine metabolites and suffering from concomitant Epstein-Barr virus infection. A few cases of lymphomas have occurred in patients with Crohn's disease treated with infliximab, only one of whom showed the presence of the Epstein-Barr virus genome. We here describe the case of a patient with steroid-dependent ileal Crohn's disease treated with azathioprine and a single infusion of infliximab, who developed a diffuse large B cell ileal lymphoma. Epstein-Barr virus genome was detected in the neoplastic cells by means of polymerase chain reaction. Epstein-Barr virus may be detected in the neoplastic tissues of lymphomas of patients with Crohn's disease treated with immunosuppressants and infliximab. The identification of such cases may help to define the frequency of this association and how to manage the lymphoproliferative disorder.

Adult↗

Effects of modified sham feeding on ghrelin levels in healthy human subjects.

The mechanisms involved in the preprandial rise and postprandial fall of circulating ghrelin levels are as yet unknown. Many hormonal and metabolic responses to nutrient intake begin during the cephalic or preabsorptive phase and are mostly mediated by the autonomous nervous system. The aim of the present study was to investigate the effects of the cephalic phase on ghrelin response to feeding in human subjects. The modified sham feeding (MSF), a well established technique in which nutrients are smelled, chewed, and tasted, but not swallowed, was used. Sixteen healthy volunteers (seven men and nine women; mean age +/- sd: 31 +/- 8 yr; body mass index, 22 +/- 3 kg/m(2)) were studied after overnight fasting. Seven of them received a standardized mixed meal, and nine underwent MSF. Blood samples for ghrelin, insulin, and glucose were taken at time -30, 0, 15, 30, 45, 60, 120 min during both tests. Pancreatic polypeptide determinations were evaluated at all times as markers of vagal activity only during MSF. Ghrelin levels significantly increased from time -30 to 0 min before the two tests, then significantly decreased: after the real feeding from 933 +/- 479 pg/ml (277 +/- 142 pmol/liter) to 455 +/- 185 pg/ml (135 +/- 55 pmol/liter; P < 0.05), and after the sham feeding from 917 +/- 313 pg/ml (272 +/- 93 pmol/liter) to 519 +/- 261 pg/ml (154 +/- 77 pmol/liter; P < 0.05). There were no significant differences between the patterns of the responses as evaluated by ANOVA (P = 0.863). As expected after MSF, plasma pancreatic polypeptide concentrations promptly increased from 58 +/- 29 pg/ml (14 +/- 7 pmol/liter) to 113 +/- 38 pg/ml (27 +/- 9 pmol/liter) at 15 min (P < 0.01). Both insulin and glucose levels increased during the actual mixed meal, whereas they were not significantly modified by MSF. In conclusion, circulating ghrelin concentrations are decreased by sham feeding as they are by real feeding in humans. These findings underline the importance of the cephalic response to nutrient intake, i.e. the role of vagal activity, in the control of ghrelin secretion.

Adult↗

Severe liver fibrosis or cirrhosis: accuracy of US for detection--analysis of 300 cases.

PURPOSE: To determine the accuracy of various ultrasonographic (US) signs for assessment of the degree of liver fibrosis, with histologic results as reference standard. MATERIALS AND METHODS: Three hundred consecutive asymptomatic patients with at least 6 months of increased levels of aspartate aminotransferase and/or alanine aminotransferase underwent liver US and biopsy. The estimated pretest probability of severe fibrosis or cirrhosis was 35%. Three US parameters were investigated: liver surface nodularity, caudate lobe hypertrophy, and pattern of hepatic venous blood flow. US results were compared with histologic results obtained after liver biopsy, which constituted the reference standard for diagnosis of severe fibrosis or cirrhosis. The degree of fibrosis was graded according to METAVIR criteria, with stages 3 and 4 considered together. Data were analyzed with kappa and chi2 statistics. Sensitivity, specificity, positive and negative likelihood ratios, and posttest probability were calculated for each US sign. RESULTS: In 107 (36%) patients with severe fibrosis (n = 34) or cirrhosis (n = 73), liver surface nodularity had the highest diagnostic accuracy, with specificity of 95% and positive and negative likelihood ratios 11.6 and 0.51, respectively. When liver surface nodularity was considered alone, posttest probability of severe fibrosis or cirrhosis increased from 35% to 86%. When caudate lobe hypertrophy and hepatic venous blood flow were also taken into account, posttest probability increased by only 2% (ie, to 88%). CONCLUSION: US determination of liver surface nodularity is an accurate method for identifying the subset of asymptomatic patients with severe liver fibrosis or cirrhosis, which indicates a worse prognosis.

Adolescent↗