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Biomedical subjects

R de Franchis

Publications and source records attributed to R de Franchis.

At least 19 recordsLinked to original sources
PubMed2001

Natural history of portal hypertension in patients with cirrhosis.

All patients with cirrhosis will eventually develop portal hypertension and esophagogastric varices. Bleeding from ruptured esophagogastric varices is the most severe complication of cirrhosis and is the cause of death in about one third of patients. The rate of development and growth of esophageal varices is poorly defined but in general seem to be related to the degree of liver dysfunction. Once varices have formed, they tend to increase in size and eventually to bleed. In unselected patients, the incidence of variceal bleeding is about 20% to 30% at 2 years. Variceal size is the single most important predictor of a first variceal bleeding episode. Several prognostic indexes based on endoscopic and clinical parameters have been developed to predict the risk of bleeding; however, their degree of accuracy is unsatisfactory. Death caused by uncontrolled bleeding occurs in about 6% to 8% of patients; the 6-week mortality rate after a variceal hemorrhage is 25% to 30%. There are no good prognostic indicators of death caused by uncontrolled bleeding or death within 6 weeks. Untreated patients surviving a variceal hemorrhage have a 1- to 2-year risk of rebleeding of about 60% and a risk of death of about 40% to 50%. The risk of bleeding is greatest in the first days after a bleeding episode and slowly declines thereafter. All patients surviving a variceal hemorrhage must be treated to prevent rebleeding. Varices can also be found in the stomach of cirrhotic patients, alone or in association with esophageal varices. Gastric varices bleed less frequently but more severely than esophageal varices. Portal hypertensive gastropathy is a common feature of cirrhosis, and its prevalence parallels the severity of portal hypertension and liver dysfunction. Portal hypertensive gastropathy can progress from mild to severe and vice-versa or even disappear completely. Acute bleeding from portal hypertensive gastropathy seems to be relatively uncommon, and less severe than bleeding from varices.

Esophageal and Gastric Varices↗
PubMed2001

Reduced free protein S levels in patients with inflammatory bowel disease: prevalence, clinical relevance, and role of anti-protein S antibodies.

We evaluated free plasma levels of protein S, a natural anticoagulant factor, the prevalence of anti-protein S antibodies, a possible cause of protein S deficiency, and their correlation with anti-phospholipid antibodies in 53 patients with inflammatory bowel disease (IBD) and 53 age- and sex-matched controls. Mean free plasma protein S levels (+/- SD) were significantly lower in IBD patients (0.98+/-0.32 IU/ml) than in controls (1.06+/-0.28 IU/ml) (P < 0.05); only one patient showed protein S deficiency. Specific antibodies to protein S were found in four IBD patients (7.5%) and in one control (1.9%) (P = NS). Five IBD patients (9.4%) and none of the controls showed anti-phospholipid antibodies (P < 0.06). No correlation was found between free protein S levels and anti-protein S antibodies or between anti-protein S and anti-phospholipid antibodies. In conclusion, free plasma protein S levels are slightly but significantly decreased in IBD patients. The prevalence of anti-protein S and antiphospholipid antibodies is increased in IBD patients. Anti-protein S antibodies do not appear to determine low protein S levels or to overlap with or belong to anti-phospholipid antibodies.

Adult↗
PubMed2001

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study.

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.

Administration, Oral↗
PubMed2000

Folate pathway gene alterations in patients with neural tube defects.

Periconceptional folate supplementation reduces the recurrence and occurrence risk of neural tube defects (NTD) by as much as 70%, yet the protective mechanism remains unknown. Inborn errors of folate and homocysteine metabolism may be involved in the aetiology of NTDs. Previous studies have demonstrated that both homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, and combined heterozygosity for the C677T and for another mutation in the same gene, the A1298C polymorphism, represent genetic risk factors for NTDs. In an attempt to identify additional folate related genes that contribute to NTD pathogenesis, we performed molecular genetic analysis of folate receptors (FRs). We identified 4 unrelated patients out of 50 with de novo insertions of pseudogene (PS)-specific mutations in exon 7 and 3'UTR of the FRalpha gene, arising by microconversion events. All of the substitutions affect the carboxy-terminal amino acid membrane tail, or the GPI anchor region of the nascent protein. Furthermore, among 150 control individuals, we also identified one infant with a gene conversion event within the FRalpha coding region. This study, though preliminary, provides the first genetic association between molecular variations of the FRalpha gene and NTDs and suggests that this gene can act as a risk factor for human NTD.

3' Untranslated Regions↗
PubMed2000

Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection.

No data are available about the amount of hepatitis B virus (HBV) genomes in liver of patients with chronic HBV infection. The aim of this study was to quantify the intrahepatic HBV DNA in hepatitis B surface antigen (HBsAg)-positive patients with either active or suppressed viral replication and in HBsAg-negative subjects with occult HBV infection. We optimized the Roche "Amplicor HBV Monitor" kit for quantifying liver HBV DNA and analyzed hepatic DNA extracts and serum samples from 19 HBs-Ag-positive and 43 HBsAg-negative individuals. Eight of the HBsAg carriers had active HBV replication, and for 3 of them we analyzed samples obtained before and at the end of 1 year of lamivudine treatment. Five hepatitis Delta virus (HDV) coinfected patients and 6 healthy HBsAg carriers had inhibited HBV activity. Among the HBsAg-negative subjects 21 had occult HBV infection and 22 had no evidence of HBV infection. The median of HBV genomes per microgram of liver DNA milliliter of serum was 34,500 to 2,620,000 in patients with active viral replication, 20,000 to 3,900, 000 before and 10,000 to 2,800 at the end of therapy in lamivudine-treated individuals, 9,800 to 600 in HDV-infected individuals, and 7,450 to 17,400 in healthy HBsAg carriers. These data indicate that cases with suppressed HBV activity, despite the very low levels of viremia, maintain a relatively high amount of intrahepatic viral genomes. This virus reservoir is likely involved in HBV reactivation, which is usually observed after stopping lamivudine treatment. Finally, the analysis of cases with occult HBV infection showed that the assay we used was able to specifically detect and quantify as few as 100 copies of viral genomes per microgram of liver DNA.

Adult↗
PubMed2000

Prevalence and risk factors of Helicobacter pylori-negative peptic ulcer: a multicenter study.

Peptic ulcer disease (PUD) has been described in the absence of Helicobacter pylori (Hp) infection, suggesting that different factors are involved in its etiopathogenesis. We investigated prevalence and characteristics of Hp-negative (Hp-) PUD in an area of Northern Italy and calculated the rate of Hp-positive (Hp+) patients with PUD in whom Hp might be coincidental and not causal. Four hundred nine consecutive patients with endoscopically diagnosed PUD were enrolled in seven hospitals. Hp infection was assessed by rapid urease test and histologic examination. The attributable risk percentages in different age groups were calculated by appropriate formulas. Of 409 patients, 31 (7.6%) were Hp- (gastric, 8.3%; duodenal, 7.6%). Age, nonsteroidal antiinflammatory drug (NSAID) consumption, and complication rates were significantly higher in Hp-than Hp+ patients with duodenal ulcers (DUs). Of the Hp-patients with DU, 58% did not use NSAIDs. In patients with Hp+ DU, the attributable risk percentage for Hp infection in patients aged <40 years, 40-60 years, or >60 years was 98%, 88%, and 66%, respectively. The prevalence of Hp- PUD was about 8%, mainly unrelated to any known etiologic factor. In about one-third of Hp+ patients with PUD aged over 60 years, Hp infection might be coincidental and not causal.

Adult↗
PubMed2000

The natural history of ulcerative proctitis: a multicenter, retrospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII).

OBJECTIVE: The aim of this study was to evaluate the clinical features and the long term evolution of patients with a well defined initial diagnosis of ulcerative proctitis. METHODS: Patients with an original diagnosis of ulcerative proctitis who had been seen at any of 13 institutions from 1989 to 1994 were identified. Data on disease onset and subsequent evolution were recorded. In addition, 575 patients with more extensive disease, treated in the same centers, were used as controls. RESULTS: A total of 341 patients satisfied the inclusion criteria. The percentage of smokers in these patients was slightly lower than in controls; no differences were found in the other clinical/demographic variables evaluated. A total of 273 patients entered long term follow-up (mean, 52 months). Proximal extension of the disease occurred in 74 of them (27.1%). The cumulative rate of proximal extension and of extension beyond the splenic flexure was 20% and 4% at 5 yr and 54% and 10% at 10 yr, respectively. The risk of proximal extension was higher in nonsmokers, in patients with >3 relapses/yr, and in patients needing systemic steroid or immunosuppressive treatment. Refractory disease was confirmed as an independent prognostic factor at multivariate analysis. CONCLUSIONS: Proximal extension of ulcerative proctitis is frequent and may occur even late after the original diagnosis. However, the risk of extension beyond the splenic flexure appears to be quite low. Smoking seems to be a protective factor against proximal extension, whereas refractoriness is a risk factor for proximal extension of the disease.

Adolescent↗
PubMed2000

Contribution of the cystathionine beta-synthase gene (844ins68) polymorphism to the risk of early-onset venous and arterial occlusive disease and of fasting hyperhomocysteinemia.

The frequency of the heterozygous 844ins68 mutation of the cystathionine beta-synthase (CBS) gene and of its association with the homozygous C677T transition of the methylenetetrahydrofolate reductase (MTHFR) gene, plasma fasting tHcy, folate and vitamin B12 levels were evaluated in 309 consecutive patients with objectively diagnosed early-onset venous (n = 200) or arterial thromboembolic disease (n = 109) recruited over 25 months in Milan (North Italy) and Naples (South Italy). The above gene polymorphisms were also evaluated in a population of 787 unmatched controls, 204 of whom--similar to patients for age- and sex-distribution--had fasting tHcy, vitamins and activated protein C resistance measured in their plasma. Moderate fasting hyperhomocysteinemia was detected in 15.5% of patients and in 5.9% of 204 controls (Mantel-Haenszel OR after stratification for type of occlusive disease and gender: 2.88; 1.48-5.32). The frequencies of the 677TT mutation of the MTHFR gene and of the heterozygous 844ins68 insertion of the CBS gene were not significantly different in the patient (19.4% and 6.9%) and the control population (16.5% and 7.8%), but the association of the two gene polymorphisms found in 3.9% of patients and in 1.1% of controls - was significantly associated with an increased risk of venous or arterial occlusive diseases (RR = 3.63; 1.48-8.91). The MTHFR 677TT mutation (RR: 6.92; 3.86-12.4) and its association with the 844ins68 insertion (RR: 21.9; 8.35-57.4), but not the isolated insertion (RR: 0.71), were more frequent in patients and controls with fasting hyperhomocysteinemia than in normohomocysteinemic subjects, irrespective of the type of occlusive disease (venous or arterial). When adjusted for determinants of hyperhomocysteinemia in the patient and the control populations (generalized linear model), fasting tHcy levels were significantly higher in subjects with association of the two gene abnormalities (24.2+/-3.8 micromol/L) than in subjects with the MTHFR 677TT mutation only (14.0+/-5.8 micromol/L, p = 0.004). Activated protein C resistance was significantly more prevalent in venous patients (9.9%) than in controls (3.9%, OR = 2.69; 1.08-6.88). Six of 21 venous patients with APC-resistance also had hyperhomocysteinemia (RR = 5.04; 0.68-37.6), but isolated fasting hyperhomocysteinemia retained statistical significance for the association with venous occlusive disease (RR = 2.84; 1.34-6.01). Heterozygosity for the 844ins68 mutation of the CBS gene is not per se a risk factor for premature arterial and/or venous occlusive diseases. However, when detected in combination with thermolabile MTHFR, it increases by almost 4-fold the risk of occlusive diseases (arterial and/or venous), by increasing the risk and the degree of fasting hyperhomocysteinemia.

Adult↗
PubMed1999

Cystathionine beta-synthase mutations in homocystinuria.

The major cause of homocystinuria is mutation of the gene encoding the enzyme cystathionine beta-synthase (CBS). Deficiency of CBS activity results in elevated levels of homocysteine as well as methionine in plasma and urine and decreased levels of cystathionine and cysteine. Ninety-two different disease-associated mutations have been identified in the CBS gene in 310 examined homocystinuric alleles in more than a dozen laboratories around the world. Most of these mutations are missense, and the vast majority of these are private mutations. The two most frequently encountered of these mutations are the pyridoxine-responsive I278T and the pyridoxine-nonresponsive G307S. Mutations due to deaminations of methylcytosines represent 53% of all point substitutions in the coding region of the CBS gene.

CpG Islands↗
PubMed1999

Four novel mutations in the cystathionine beta-synthase gene: effect of a second linked mutation on the severity of the homocystinuric phenotype.

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is frequently caused by missense mutations. In this article, we report four novel missense mutations in the CBS gene: 172C-->T (R58W) linked in cis with A114V; 376A-->G (M126V); 904G-->A (E302K); and 1006C-->T (R336C). The CBS activity of the corresponding mutant enzymes expressed in Escherichia coli was greatly diminished, confirming the pathogenicity of these mutations. Western analysis showed that the R58W+A114V and M126V mutant enzymes were unstable in E. coli, while the E302K subunits were partially degraded to shorter products. Using site-directed mutagenesis we found that CBS containing either the R58W or A114V as the only mutations demonstrated 18% and 46% of normal activity, respectively. Both mutant forms of CBS were stable in E. coli. When these two mutations were expressed in cis, the resultant mutant protein exhibited activity 1.3% that of a control. All these in vitro results were in good agreement with the clinical manifestation in these patients. The Italian patient 2241, an A114V+R58W/M126V compound heterozygote, exhibited severe pyridoxine nonresponsive homocystinuria, while another Italian patient 2242, with an A114V/E302K genotype, responded to pyridoxine treatment and had a much milder phenotype. The third patient 3064, an English compound heterozygote for two severe mutations R336C and G307S, was B6 nonresponsive. This report of a ninth homocystinuric allele carrying two mutations in cis raises the possibility that double mutant alleles may be underestimated in homocystinuric patients. In this context, a search for additional mutations in cis may sometimes be necessary to establish a good genotype-phenotype relationship.

Alleles↗
PubMed1999

Cost analysis for the prevention of variceal rebleeding: a comparison between transjugular intrahepatic portosystemic shunt and endoscopic sclerotherapy in a selected group of Italian cirrhotic patients.

The aim of the present study was to compare the cumulative cost of the first 18-month period in a selected group of Italian cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic sclerotherapy (ES) to prevent variceal rebleeding. Thirty-eight patients enrolled in a controlled trial were considered (18 TIPS and 20 sclerotherapy). The number of days spent in the hospital for the initial treatment and during the follow-up period were defined as the costs of hospitalization. ES sessions, TIPS procedures, angioplasty or addition of a second stent to maintain the shunt patency, were defined as the costs of therapeutic procedures. The two groups were comparable for age, sex, and Child-Pugh score. During the observation period 4 patients died in the TIPS group, and 2 died and 1 was transplanted in the sclerotherapy group. The rebleeding rate was significantly higher in the sclerotherapy group. Despite this, the number of days spent in the hospital was similar in the two groups. This was because of a higher number of hospital admissions for the treatment of hepatic encephalopathy and shunt insufficiency in the TIPS group. The therapeutic procedures were more expensive for TIPS. Consequently, the cumulative cost was higher for patients treated with TIPS than for those treated with sclerotherapy. The extra cost was because of the initial higher cost of the procedure and the difference was still maintained at the end of the 18-month follow-up. When the cumulative costs were expressed per month free of rebleeding, the disadvantage of TIPS disappeared. In conclusion, a program of prevention of variceal rebleeding with TIPS, despite the longer interval free of rebleeding, is not a cost-saving strategy in comparison with sclerotherapy.

Costs and Cost Analysis↗
PubMed1999

Fasting, postprandial, and post-methionine-load homocysteinaemia and methylenetetrahydrofolate reductase polymorphism in vascular disease.

Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) is a common genetic cause of increased homocysteine (HCY) levels. Post-methionine-load HCY concentrations allow identification of certain cases of hyperhomocysteinaemia not demonstrated by fasting levels. This study investigated the relationship between MTHFR polymorphism and (1) fasting HCY levels (77 patients); (2) post-methionine HCY levels (54 patients); and (3) postprandial HCY concentrations (36 patients) in cardiovascular disease. As expected, mean fasting HCY value was higher in the +/+ patients. Moreover, patients who were homozygous for the mutation exhibited significantly increased mean post-methionine-load HCY; in contrast, literature results are conflicting. Mean postprandial HCY, which is not known to be increased in controls, was also increased in the (+/+) patients, although the difference did not reach statistical significance, probably owing to the small size of the sample. MTFHR polymorphism is known to be aggravated by a drop in circulating folate. Additional risk factors may be more prevalent in patients with cardiovascular disease.

Adolescent↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

[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↗