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Biomedical subjects

R de Franchis

Publications and source records attributed to R de Franchis.

At least 55 records · Page 3Linked to original sources

Endoscopic treatments for portal hypertension.

Endoscopic treatments for bleeding gastroesophageal varices include injection sclerotherapy, variceal obturation with tissue adhesives, and variceal rubber band ligation. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from esophageal varices. Although few trials have been published so far, some evidence suggests that the early administration of vasoactive drugs (somatostatin, octreotide, or terlipressin) is safe and may increase the efficacy of endoscopic treatments. Banding ligation is the optimal endoscopic treatment for the prevention of rebleeding from esophageal varices. The use of tissue adhesives and thrombin as injectates to treat bleeding fundal gastric varices and esophageal varices not responding to vasoactive drugs or sclerotherapy is promising but needs further assessment by means of randomized controlled trials. As of today, endoscopic treatments are not recommended for the primary prophylaxis of variceal bleeding.

Acute Disease↗

Serum von Willebrand factor levels in patients with inflammatory bowel disease are related to systemic inflammation.

BACKGROUND: Increased levels of circulating von Willebrand factor (vWF) have been found in patients with inflammatory bowel disease (IBD); this increase may reflect either endothelial damage or systemic inflammation. Our aim was to evaluate serum vWF levels in patients with IBD and their correlation with clinical and biochemical disease activity. METHODS: We evaluated serum vWF levels in 32 patients with ulcerative colitis (UC) (10 active with increased acute-phase reactants (APR), 6 active with normal APR, 16 in remission), 27 with Crohn disease (CD) (10 active, 12 quiescent, and 5 quiescent with increased APR), and 31 healthy controls. RESULTS: Mean levels of vWF were 100.1 (standard deviation (s), 51.4) in IBD and 89.9 (s, 36.9) in controls (P = 0.33). Only five (8.47%) patients (three with active UC, one with active CD, and one with inactive CD but increased APR) showed circulating vWF levels higher than the upper limit of normal (150), compared with 1 (3.2%) of controls (P = 0.32). Among CD patients vWF levels were 80.0+/-25.4 in patients with quiescent disease and normal APR, 123.3+/-63.4 in patients with active disease (P = 0.04 versus inactive with normal APR), and 135.8+/-90.0 in patients with quiescent disease and increased APR (P = 0.059 versus inactive with normal APR). Among UC patients vWF levels were 82.7+/-35.6 in patients with quiescent disease and normal APR and 125.1+/-54.2 in those with active disease and increased APR (P = 0.002). Overall, mean vWF levels were significantly higher in patients with increased APR than in patients with normal APR (P = 0.0005) and controls (P = 0.009). CONCLUSIONS: Our data show slight but significant increases in serum vWF levels in patients with IBD, which are correlated with signs of systemic inflammation.

Acute-Phase Proteins↗

Emerging strategies in the management of upper gastrointestinal bleeding.

Variceal hemorrhage is the most serious complication of portal hypertension and is associated with a high mortality rate. The first stage of treatment is to stabilize the patient, followed by emergency diagnostic endoscopy to identify the source of bleeding. If active variceal bleeding is found, endoscopic intervention by sclerotherapy or band ligation is performed to induce hemostasis. Sclerotherapy achieves hemostasis through the induction of thrombosis and/or by external compression of the vessel; band ligation by physical constriction of the varix. Both techniques are difficult to perform during active bleeding. This has prompted the search for improved treatment protocols. Vasoactive drugs which lower portal pressure have been used for years as an alternative to endoscopic treatment. Recently, the combined use of such drugs and either sclerotherapy or banding has been proposed. Data from several trials have suggested that pharmacotherapy in combination with endoscopic intervention is more effective than endoscopic treatment alone. Furthermore, pharmacotherapy continued for 5 days following endoscopy significantly reduces the incidence of early rebleeding. Thus, therapeutic regimens combining vasoactive drugs and endoscopic therapy are likely to replace, in the near future, the usual approaches based on endoscopic or pharmacological treatment alone.

Endoscopy, Gastrointestinal↗

[The topical therapy of ulcerative colitis. A multicenter study with beclomethasone dipropionate foam].

BACKGROUND AND AIMS: The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis. METHODS: The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%). RESULTS: Endoscopic parameters showed an improvement after 28 days of treatment in 74.5% of patients; a clinical improvement was achieved in 65.2% of cases. In percentage terms of the mean value of all the improved parameters, histological parameters were altered in 56.9% of patients. With regard to tolerability 82% of patients judged the treatment to be good/excellent. CONCLUSIONS: In conclusion, in line with recent reports regarding other pharmaceutical forms of BDP, including the use of rectal foam, these data confirm the efficacy and tolerability of this molecule and emphasise the validity of its use in the treatment of ulcerative colitis and proctosigmoiditis.

Administration, Topical↗

[Topical beclomethasone dipropionate (BDP) in intestinal inflammatory diseases: the results of a multicentre trial].

The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas and suppositories and in a double-blind protocol vs mesalazine using rectal enemas. A total of 47 patients suffering from ulcerous rectocolitis were enrolled in the study and treated for 42 days while undergoing endoscopic, histologic and clinical controls. In conclusion, the authors affirm that BDP may represent a useful new therapeutic instrument in the treatment of slight to moderately severe forms of inflammatory intestinal disease.

English Abstract↗

The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms.

Cystathionine beta-synthase [CBS; l-serine hydro-lyase (adding homocysteine), EC 4.2.1.22] catalyzes the first committed step of transsulfuration and is the enzyme deficient in classical homocystinuria. In this report, we describe the molecular cloning and the complete nucleotide sequence of the human CBS gene. We report a total of 28,046 nucleotides of sequence, which, in addition to the CBS gene, contains approximately 5 kb of the 5' flanking region. The human CBS gene contains 23 exons ranging from 42 to 209 bp. The 5' UTR is formed by 1 of 5 alternatively used exons and 1 invariably present exon, while the 3' UTR is encoded by exons 16 and 17. We also describe the identification of two alternatively used promoter regions that are GC rich (approximately 80%) and contain numerous putative binding sites for Sp1, Ap1, Ap2, and c-myb, but lack the classical TATA box. The CBS locus contains an unusually high number of Alu repeats, which may predispose this gene to deleterious rearrangements. Additionally, we report on a number of DNA sequence repeats that are polymorphic in North American and European Caucasians.

Alternative Splicing↗

Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: a randomized multicenter trial. Gruppo Italiano Studio TIPS (G.I.S.T.).

Transjugular intrahepatic portosystemic shunt (TIPS), a new technique for the treatment of portal hypertension, has been successful in preliminary studies to treat acute variceal hemorrhage and to prevent variceal rebleeding. The purpose of this multicenter, randomized controlled trial is to compare the efficacy of TIPS with that of endoscopic sclerotherapy in the prevention of variceal rebleeding in cirrhosis. Eighty-one cirrhotic patients, with endoscopically proven variceal bleeding, were randomized to either TIPS (38 patients) or endoscopic sclerotherapy (43 patients). Randomization was stratified according to the following: if bleeding occurred < 1 week (stratum I); if bleeding occurred 1 to 6 weeks (stratum II); and if bleeding occurred 6 weeks to 6 months (stratum III) before enrollment. Follow-up included clinical, biochemical, Doppler Ultrasound, and endoscopic examinations every 6 months. During a mean follow-up of 17.7 months, 51% of the patients treated with sclerotherapy and 24% of those treated with TIPS rebled (P = .011). Mortality was 19% in sclerotherapy patients and 24% in TIPS patients (P = .50). Hepatic encephalopathy (HE) developed in 26% and 55%, respectively (P = .006). A separate analysis of the three strata showed that TIPS was significantly more effective than sclerotherapy (P = .026) in preventing rebleeding only in stratum I patients. TIPS is significantly better than sclerotherapy in preventing rebleeding only when it is performed shortly after a variceal bleed; however, TIPS does not improve survival and is associated with a significantly higher incidence of HE. The overall performance of TIPS does not seem to justify the adoption of this technique as a first-choice treatment to prevent rebleeding from esophageal varices in cirrhotic patients.

Aged↗

Long-term observation of the perinuclear anti-neutrophil cytoplasmic antibody status in ulcerative colitis patients.

BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) have been regarded as a possible immunogenetic marker of ulcerative colitis. If this were true, the p-ANCA status of a given patient should be constant over time; however, little information is available on this issue. METHODS: One hundred and forty-five sera collected from 40 ulcerative colitis patients during a mean follow-up period of 50.6 months were tested for p-ANCA reactivity by indirect immunofluorescence. RESULTS: At base line 24 patients (60%) were p-ANCA-positive, with no relationship to gender distribution, age at diagnosis, disease activity, or extension. During follow-up, changes in p-ANCA status occurred in 10 patients (25%). P-ANCA positivity during follow-up was associated with more aggressive forms of disease, whereas p-ANCA negativity was associated with stable remission. CONCLUSIONS: Changes in the p-ANCA status over time occur in some ulcerative colitis patients. P-ANCA behaviour is associated with different clinical patterns of disease.

Adolescent↗

Recognition of bactericidal/permeability-increasing protein by perinuclear anti-neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients: prevalence and clinical significance.

BACKGROUND: The aim of this study was to evaluate a) the role of bactericidal/permeability-increasing protein (BPI) as a possible antigen determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI antibodies in patients with ulcerative colitis on the basis of their p-ANCA status. METHODS: p-ANCA and anti-BPI antibodies were evaluated by means of indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a group of 112 ulcerative colitis patients (including 42 patients subjected to proctocolectomy) well defined as far as their clinical features and p-ANCA status. RESULTS: Anti-BPI antibodies were detected in 24% of non-operated patients and were significantly more frequent in p-ANCA-positive patients (32% versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI antibodies was similar in non-operated and operated patients and was high in men, in patients with an extensive and aggressive disease, and in patients developing pouchitis after surgery. CONCLUSIONS: These data indicate that BPI is a neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis sera. The presence of anti-BPI antibodies appears to identify further immunologic and clinical heterogeneity in ulcerative colitis.

Adolescent↗

Longer treatment with vasoactive drugs to prevent early variceal rebleeding in cirrhosis.

Bleeding oesophageal varices (BOV), resulting from portal hypertension, can prove fatal. Not only is it important to stop the initial bleeding, which may lead to hypovolaemic shock, but also to treat this condition in the longer term, and, consequently, the prevention of rebleeding needs to be addressed. This review highlights the current findings on the haemostatic drug, terlipressin, focusing particular attention on the potential for longer-term treatment strategies in the prevention of rebleeding. The efficacy of terlipressin in treating acute BOV, its low incidence of severe side-effects (comparable to those of somatostatin) and its favourable comparison with sclerotherapy in the prevention of early rebleeds, all indicate the potential for terlipressin administration to be extended to 5 days in the longer-term treatment of BOV. In addition, terlipressin administration, in conjunction with sclerotherapy, can significantly reduce the likelihood of rebleeding compared with sclerotherapy alone and further supports its potential use in the longer-term treatment of BOV.

Acute Disease↗

The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy.

OBJECTIVE: To estimate the risk for spina bifida associated with the common mutation C677T of the MTHFR gene in a country with a relatively low prevalence of NTDs. DESIGN: Case-control study. SUBJECTS CASES: 203 living patients affected with spina bifida (173 myelomeningocele and 30 lipomeningocele); controls: 583 subjects (306 young adults and 277 unselected newborns) from northern and central-southern Italy. SETTING CASES: three spina bifida centres; young adult controls: DNA banks; newborn controls: regional neonatal screening centres. MAIN OUTCOME MEASURES: Prevalence of the C677T genotypes in cases and controls by place of birth; odds ratios for spina bifida and estimated attributable fraction. RESULTS: The prevalence of T/T, T/C, and C/C genotype was 16.6%, 53.7%, and 29.7% in controls and 25.6%, 43.8%, and 30.6% in cases, respectively. We found no differences between type of defect or place of birth. The odds ratio for spina bifida associated with the T/T genotype v C/C plus T/C was 1.73 (95% CI 1.15, 2.59) and the corresponding attributable fraction was 10.8%. No increased risk was found for heterozygous patients (OR=0.79, 95% CI 0.53-1.18). CONCLUSION: This study, as well as the meta-analysis we updated, shows that homozygosity for the MTHFR C677T mutation is a moderate risk factor in Europe, and even in Italy where there is a relatively low prevalence of spina bifida. The estimated attributable fraction associated with this risk factor explains only a small proportion of cases preventable by periconceptional folic acid supplementation. Thus, other genes involved in folate-homocysteine metabolism, their interaction, and the interaction between genetic and environmental factors should be investigated further.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

High prevalence of hyperchomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications?

BACKGROUND AND AIMS: Why patients with inflammatory bowel disease are at increased risk for thrombosis is unknown. Since they may have impaired absorption of vitamins that regulate the metabolism of homocysteine, we tested the hypothesis that they have hyperhomocysteinemia, an established risk factor for arterial and venous thrombosis. METHODS: The concentrations of total homocysteine (tHcy), folate and cobalamin were measured in blood samples from 61 consecutive patients with inflammatory bowel disease and 183 age- and sex-matched healthy controls. RESULTS: The mean (+/- S.D.) concentration of plasma tHcy was higher in patients (12.2 +/- 7.7 micromol/l) than in controls (10.5 +/- 4.6, p = 0.045). Eight patients (13%) had concentrations of tHcy higher than the 95th percentile of distribution among controls, as compared with 9 healthy controls (5%, p = 0.04). The prevalence of folate deficiency was higher in patients (15%) than in controls (5%, p = 0.02). Oral administration of folate, cobalamin and pyridoxine to 15 patients for 30 days decreased their mean tHcy levels from 20.3 +/- 9.9 to 9.5 +/- 3.4 (p <0.001). CONCLUSIONS: In patients with inflammatory bowel disease there is an increased prevalence of hyperhomocysteinemia, which can be corrected by the administration of folate, cobalamin and pyridoxine. The high prevalence of hyperhomocysteinemia may account for the thrombotic risk of IBD patients; whether or not its correction will decrease the thrombotic risk should be tested in properly designed clinical trials.

Adult↗

Endoscopic treatments for portal hypertension.

Endoscopic treatments for bleeding gastro-oesophageal varices include injection sclerotherapy, variceal obturation with tissue adhesives and variceal rubber band ligation. Today, endoscopic treatments are not recommended for the primary prophylaxis of variceal bleeding. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from oesophageal varices. Its efficacy may be improved by the early administration of vasoactive drugs. Banding ligation is the optimal endoscopic treatment for the prevention of rebleeding from oesophageal varices. The use of tissue adhesives and thrombin as injectates to treat bleeding fundal gastric varices and oesophageal varices not responding to vasoactive drugs or sclerotherapy is promising but needs further assessment by means of randomized controlled trials.

Acute Disease↗

Controlled trial of oral 5-aminosalicylic acid for the prevention of early relapse in Crohn's disease.

BACKGROUND: Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrollment. AIM: To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease. METHODS: Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal. RESULTS: Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 +/- 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference +0.095; 95% CI = -0.085 to +0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease. CONCLUSIONS: Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.

Adolescent↗

High prevalence of Helicobacter pylori infection in patients with colonic adenomas and carcinomas.

In some uncontrolled studies, a high prevalence of Helicobacter pylori infection unexpectedly has been found in patients with colorectal cancer. The purpose of the study was to investigate the prevalence of H. pylori infection in patients with colonic polyps or cancer. We reviewed 50 consecutive patients with either colonic adenomas or cancer who entered a preliminary case-control study. For each patient, 2 age- and gender-matched control subjects were selected (72 males; mean age, 63.1 years). A further 44 consecutive patients (30 with polyps and 14 with cancer) subsequently were enrolled. The H. pylori prevalence in patients with either polyps or cancer was compared with that in control subjects. Anti-H. pylori immunoglobulin G antibodies were assayed by an immunoenzymatic method. The prevalence of H. pylori antibodies was 49 (49%) of 100 in control subjects, 40 (71.4%) of 56 in patients with polyps (p < 0.006 vs. control subjects), and 21 (55%) of 38 in patients with cancer (not significant). Among patients with colorectal cancer, H. pylori prevalence was 9 (69.2%) of 13 for patients evaluated at the time of diagnosis and 12 (48%) of 25 for patients evaluated 1 to 9 years after surgery. We conclude that colonic neoplastic lesions, especially adenomas, are associated with an increased prevalence of H. pylori infection. The mechanisms underlying this association need to be elucidated.

Adenoma↗

Portal hypertensive gastropathy: reproducibility of a classification, prevalence of elementary lesions, sensitivity and specificity in the diagnosis of cirrhosis of the liver. A NIEC multicentre study. New Italian Endoscopic Club.

OBJECTIVE: To classify elementary endoscopic lesions of portal hypertensive gastropathy, assess their reproducibility, prevalences, sensitivity and specificity in the diagnosis of cirrhosis of the liver. METHODS: 1) A classification of portal hypertensive gastropathy elementary lesions was defined. 2) Thirty-two endoscopists evaluated videotapes of endoscopic examinations of patients with liver cirrhosis to assess beyond-chance agreement (kappa). 3) Fifteen centres enrolled consecutive patients with or without cirrhosis of the liver and recorded portal hypertensive gastropathy pattern according to its location. RESULTS: 1) Four elementary lesions (Mosaic-Like Pattern, Red Point Lesions, Cherry Red Spots, Black-Brown Spots) were identified, and graded. 2) A fair to good beyond-chance agreement was obtained for all 4 lesions. 3) portal hypertensive gastropathy prevalence was higher in patients with cirrhosis of the liver (0.63, sensitivity) than in controls (0.17). Mosaic-like pattern was the most prevalent sign (0.54). Specificity of portal hypertensive gastropathy was 0.83. Portal hypertensive gastropathy was tentatively classified as mild or severe when mosaic-like pattern alone or red marks of any kind were present, respectively; this classification led to a further improvement in reproducibility. CONCLUSIONS: Our results suggest that a sufficient degree of agreement can be achieved in recording portal hypertensive gastropathy. Therefore, the New Italian Endoscopic Club classification should be used to evaluate the natural history of this condition.

Diagnosis, Differential↗