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Biomedical subjects

F Vilardell

Publications and source records attributed to F Vilardell.

At least 19 recordsLinked to original sources

Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer.

Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKKalpha associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKKalpha restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.

Animals↗

Continuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin.

Cirrhotic patients with ascites and low ascitic fluid total protein and/or high serum bilirubin levels are at high risk to develop the first episode of spontaneous bacterial peritonitis during long-term follow-up. The aim of the present study was to determine the efficacy of continuous long-term selective intestinal decontamination with norfloxacin in the prevention of this complication. One hundred nine cirrhotic patients with ascites and ascitic fluid total protein levels of < or = 1 g/dL or serum bilirubin levels of > 2.5 mg/dL without previous spontaneous bacterial peritonitis were prospectively randomized into two groups: group 1 (n = 56) received norfloxacin, 400 mg daily administered orally, and group 2 (n = 53) was the long-term control group, receiving norfloxacin only during hospitalization. During a mean follow-up of 43 +/- 3 weeks, there was one spontaneous bacterial peritonitis (1.8%) in group 1 and 9 (16.9%) in group 2 (P < .01). The incidence of community-acquired spontaneous bacterial peritonitis was lower in group 1 (1.8% vs. 13.2%, P < .05), whereas the incidence of nosocomial spontaneous bacterial peritonitis (0% vs. 3.7%) and the incidence of extraperitoneal infections (25% vs. 24.5%) were similar in both groups (P = NS). The actuarial probability of survival at 18 months was 75% in group 1 and 62% in group 2 (P = NS). Resistance to norfloxacin was observed in 9 of 10 (90%) Escherichia coli isolated in infections from group 1 and in 4 of 11 (36.3%) from group 2 (P < .05). The overall incidence of infections caused by norfloxacin-resistant bacteria was higher in group 1 (19.6% vs. 15%), but it did not reach statistical significance. Continuous long-term selective intestinal decontamination with norfloxacin is effective in preventing the first spontaneous bacterial peritonitis in cirrhotic patients at high risk. However, the emergence of infections caused by norfloxacin-resistant bacteria must be weighed carefully against the benefits of continuous long-term prophylaxis.

Anti-Infective Agents↗

Early microbiologic diagnosis of spontaneous bacterial peritonitis with BacT/ALERT.

BACKGROUND/AIMS: Inoculation of ascitic fluid into conventional blood culture bottles is more sensitive than conventional culture in the diagnosis of spontaneous bacterial peritonitis. BacT/ALERT is an automated colorimetric microbial detection system that has been shown to be faster than conventional blood culture bottles in the diagnosis of bacteremia. The aim of the study was to compare the BacT/ALERT system with the conventional culture and the conventional blood culture bottles method in the diagnosis of spontaneous bacterial peritonitis. METHODS: All the ascitic fluid samples from patients with cirrhosis hospitalized in our Department between September 1992 and May 1994 (n=1032) were prospectively evaluated. In all cases, an aliquot of ascitic fluid was sent for Gram's stain and conventional culture, and 20 ml were inoculated at the bedside into blood culture bottles: 10 ml into conventional blood culture bottles and 10 ml into BacT/ALERT. RESULTS: Thirty ascitic fluid infections (23 spontaneous bacterial peritonitis and 7 neutrocytic ascites) and 20 bacterascites were diagnosed. Conventional culture was positive in 10/30 ascitic fluid infections (33.3%), conventional blood culture bottles in 22/30 (73.3%) (p<0.01 compared to conventional culture) and BacT/ALERT in 20/30 (66.6%) (p<0.05 compared to conventional culture, pNS compared to conventional blood culture bottles). The time elapsed for culture positivity was 43.4+/-34.2 h for conventional blood culture bottles and 13.3+/-9.2 h for BacT/ALERT (p<0.001). Thirteen of the 23 cases of spontaneous bacterial peritonitis (56.5%) were detected within the first 12 h with BacT/ALERT, as compared to only three (13%) with conventional blood culture bottles (p<0.03). CONCLUSION: The automated system BacT/ALERT provides an earlier microbiologic diagnosis of spontaneous bacterial peritonitis than conventional blood culture bottles with similar sensitivity.

Anti-Bacterial Agents↗

Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding.

BACKGROUND: Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS: Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS: Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS: As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.

Actuarial Analysis↗

Gastric emptying of two radiolabelled antacids with simultaneous monitoring of gastric pH.

The aim of this study was to assess the gastric emptying rate of two antacids using an scintigraphic technique and simultaneous monitoring of gastric pH in 16 healthy male volunteers. Ten ml of Talcid (hydrotalcite 1 g) and Maalox (Mg-Al-hydroxide), with a similar neutralization capacity, were labelled with technetium-99m using a pyrophosphate bridge. Labelled antacids were given on separate days (within 2 weeks), 1 h after a standard meal. Intragastric pH was measured for at least 4 h, using ambulatory pH-metry with a dual-crystant antimony catheter. Continuous monitoring was started 1 h prior to the meal (baseline) and lasted 3 h (post-prandial, post-antacid and final periods). The antacid capacity of labelled and unlabelled antacids was similar. The mean percentages of antacids retained in the stomach fitted a linear model. The mean half-emptying time of Talcid was 63.9 +/- 27.9 min, while that of Maalox was 57.3 +/- 23.9 min (P = NS). The recordings of gastric pH (mean values of pH for each period) showed a similar profile for both antacids. The mean pH (Maalox vs Talcid) was 1.69 vs 2.07 in the baseline period, 1.95 vs 1.93 in the post-prandial period, 1.79 vs 1.15 in the post-antacid period (P = NS) and 0.4 vs 0.52 in the final period (P < 0.05 vs prior periods). In conclusion, the gastric emptying of Talcid and Maalox was similar and pH profiles were parallel and remained unchanged for the two antacids within the first hour of intake. A significant decrease in pH was observed 1 h after intake of the antacids, suggesting a possible rebound effect.

Adult↗

Prevalence of thyroid autoantibodies is not increased in blood donors with hepatitis C virus infection.

Serum autoimmune reactions are found in many patients with hepatitis C. A high prevalence of thyroid dysfunction and antithyroid antibodies in patients with chronic hepatitis C was recently reported. We have compared the prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with hepatitis C virus (HCV) infection (study group) and in seronegative anti-HCV donors (control group). One hundred and ninety-two blood donors were studied: 96 were anti-HCV positive by ELISA 2 (48 males and 48 females; age 48 +/- 12.9 years, mean +/- SD), and 96 were HCV seronegative (55 males and 41 females; age 37 +/- 14.8 years). In all patients, serum TSH (0.25-4.2 mU/l) and fT4 (9-23 pmol/l) were measured by immunochemiluminiscent assays and antithyroid peroxidase antibodies (normal < 100 U/ml) by RIA. In all anti-HCV positive donors, hepatitis C viremia was tested using the nested polymerase chain reaction. Thyroid dysfunction was found in three females (3.1%) in the anti-HCV positive group (three cases of hypothyroidism), and in four (4.1%) anti-HCV negative blood donors (three cases of hypothyroidism, two females and one male; one case of hyperthyroidism, a female), (p = NS). Antithyroid peroxidase antibody titers were above normal values in 5 (5.2%) anti-HCV positive individuals and in eight (8.3%) anti-HCV negative blood donors (p = NS). These results do not show an increase prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with HCV infection when compared with a control group.

Adult↗

Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study.

BACKGROUND AND STUDY AIMS: Although high rates of initial hemostasis can be achieved with endoscopic injection therapy in actively bleeding ulcers, the incidence of rebleeding is not negligible. Optimal conditions for clotting may require achieving deep and sustained acid inhibition to avoid the deleterious effect of acid and pepsin secretions on the hemostatic process. The aim of this study was to assess whether omeprazole could improve the efficacy of ranitidine as an adjunct treatment in endoscopic injection therapy to avoid rebleeding. PATIENTS AND METHODS: Eighty-six patients with active arterial bleeding from a peptic ulcer disclosed at emergency endoscopy were included in this prospective trial. All patients received injections of 1:10,000 adrenaline. Subsequently, they were randomized to receive either intravenous omeprazole (n = 45), with an initial dose of 80 mg followed by 40 mg every eight hours for four days and thereafter with oral administration; or ranitidine (n = 41), 50 mg every six hours for 12 to 24 hours and thereafter with oral administration. RESULTS: The two groups were well matched in terms of clinical and endoscopic data. There were no statistically significant differences between the groups with regard to: further bleeding (29% in both groups), need for emergency surgery (20% in the omeprazole group vs. 22% in the ranitidine group), transfusion requirements (2.4 +/- 2.2 vs. 2.2 +/- 2.1 units), length of hospital stay (14.1 +/- 13.9 vs. 15.3 +/- 15.4 days), or mortality (7% vs. 2%). CONCLUSIONS: Our results suggest that omeprazole does not improve the efficacy of ranitidine after endoscopic injection therapy in patients with an active arterial bleeding ulcer.

Adult↗

Comparative study of two high doses of lymphoblastoid interferon in the treatment of chronic hepatitis C: influence on the levels of ALT, viraemia and histologic activity.

Ninety consecutive patients with chronic hepatitis C were included in a randomized, uncontrolled trial to compare the efficacy of two treatment regimens, 10 MU (group A) vs 5 MU (group B), of lymphoblastoid interferon, in a step-down schedule for 24 weeks. All of the patients had antibodies against the hepatitis C virus, and all but one were HCV RNA positive in serum. The origin of the infection was attributed to blood transfusion in 30 patients and classified as sporadic in 60 patients. During treatment reduction in the ALT levels as well as the elimination of viraemia was observed in both treated groups, although these changes did not correlate significantly with the interferon dose. Nine months after the end of therapy, a sustained response was achieved in 13.6% (12/88) of the patients. Relapse in group B (87.5%) was significantly higher than in group A (59.1%). The percentage of cases which remained with undetectable HCV RNA was significantly higher for the sustained responders (66.7%) than for the non-responders (11.8%) and relapser patients (2.4%). Repeated liver biopsies showed an overall significant reduction of all the subindices of histological activity from patients with sustained response, except for fibrosis. In short: the 10 MU dosing regimen of lymphoblastoid interferon was as efficient as the 5 MU dose as it brought about a similar improvement in ALT levels, histological activity and elimination of viraemia, albeit 10 MU proved significantly more effective in the prevention of a relapse among the responders after 24 weeks therapy.

Adult↗

Escherichia coli capsular polysaccharide and spontaneous bacterial peritonitis in cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhosis. Escherichia coli is the most frequent bacterium isolated in this condition. The presence of capsular antigens, mainly the K1 capsular polysaccharide, has been associated with invasiveness in E coli infections. Capsular serotypes of E coli causing SBP were determined in 37 cirrhotic patients. Twenty-seven strains were encapsulated (72.9%), 9 of them (24.3%) with K1 capsular polysaccharide, and 10 were nonencapsulated. Patients with encapsulated E coli showed a significantly higher incidence (92.5% vs. 50%; P < .01) and number of complications per patient (1.9 +/- 1.1 vs. 0.8 +/- 1.0; P < .01) than patients with nonencapsulated strains. Although mortality was higher in patients with encapsulated strains (44.4% vs. 20%), the difference did not reach statistical significance. Considering patients infected by encapsulated strains, the incidence of complications and mortality were similar in patients with or without K1 strains. These data suggest that the presence of encapsulated strains could have a prognostic significance in SBP caused by E coli in cirrhotic patients.

Aged↗

Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma.

Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were randomly allocated to two groups: group I included 20 patients who were treated with 10 mg bid. tamoxifen and group II with 16 non-treated patients. The two groups were homogeneous according to clinical and analytical data. Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group (p = 0.01). Cumulative survival at the end of the first year was 48.5% in the treated patients and 9.1% in controls. Median survival was 261 days in the treated group vs. 172 in the non-treated group (p < 0.05). Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls, but not significantly so. Tamoxifen was well tolerated and no marked side effects were observed. In this series, tamoxifen improved survival in patients with advanced hepatocellular carcinoma.

Aged↗

Influence of the menstrual cycle and of menopause on the gastric emptying rate of solids in female volunteers.

The aim of this study was to assess the influence of the normal menstrual cycle and of menopause on the gastric emptying rate of solids. Gastric emptying was studied in 15 premenopausal and ten postmenopausal women with an isotopic technique after the ingestion of a radiolabelled test meal. Premenopausal women were studied twice: within 1 week prior to menses and again 1 week after onset of menses. Postmenopausal women were studied only once. The emptying curves of the solid component of the meal fitted a linear model. The half-emptying time was 78 +/- 5 min during the follicular phase, 75 +/- 7 min during the luteal phase and 76 +/- 6 min in postmenopausal women (differences not statistically significant). The mean percentages of the meal retained in the stomach at different time intervals were also similar in the three groups. These results suggest that the menstrual cycle does not influence the gastric emptying rate of solids, which remains unchanged in relation to the follicular phase or after menopause.

Adult↗

Prediction of therapeutic failure in patients with bleeding peptic ulcer treated with endoscopic injection.

Endoscopic injection therapy was performed in a consecutive series of 233 patients admitted for a bleeding peptic ulcer with active arterial hemorrhage or a nonbleeding visible vessel disclosed at emergency endoscopy. Further bleeding occurred in 57 cases (24.5%). The present study was conducted to evaluate whether any clinical or endoscopic features could identify the patients at high risk of therapeutic failure. Multiple logistic regression analysis showed that failure was significantly related to: (1) the ulcer location on the posterior wall (P = 0.004) or superior wall (P = 0.003) of the duodenal bulb, (2) the ulcer size (P = 0.011), and (3) the existence of associated diseases (P = 0.012). The validity of the prediction rule based on these factors was evaluated by receiver-operating characteristic curves and was confirmed and prospectively validated in an independent sample of 81 patients with a bleeding peptic ulcer treated by endoscopic injection. We conclude that once the initial control of bleeding has been achieved by injection therapy, the present prediction rule can be used to identify candidates for alternative treatment.

Duodenal Ulcer↗

Is endoscopic gastric cytology worthwhile? An evaluation of 903 cases of carcinoma.

From 1978 to 1989, 4,772 endoscopic cytological examinations of the stomach have been done in our laboratory, including 903 patients with a final diagnosis of gastric carcinoma. There were seven false-positive results among 3,810 examinations done in patients without malignant disease (specificity 99.8%). Cytology yielded positive results in 785 of 903 carcinomas (sensitivity 86.9%), while biopsies were positive in 826 of 895 cases (sensitivity 92.3%). Both techniques combined resulted in positive diagnoses in 886 of 903 malignancies (sensitivity 98.1%). Cytology was positive in 52 patients with negative biopsies as well as in eight patients in whom biopsies had not been obtained. Thus cytology added 60 positive diagnoses (6.7%) to the overall diagnostic results. These results suggest that endoscopic cytology is useful for avoiding unnecessary delays caused by having to perform repeated endoscopic biopsies. It should be done as a routine procedure in those institutions in which significant numbers of gastric carcinomas are studied and where an experienced gastrointestinal cytology laboratory is available.

Carcinoma↗

Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol.

In a prospective randomized trial involving 63 patients with bleeding peptic ulcer, we assessed whether the addition of 1% polidocanol improved the results achieved by 1/10(4) adrenaline alone for injection therapy. The inclusion criterion was the presence of active arterial bleeding or a nonbleeding visible vessel at emergency endoscopy. Thirty patients were treated with 1/10(4) adrenaline (group A) and 33 with adrenaline plus 1% polidocanol (group B). Initial hemostasis was achieved in 97% of cases in both groups and permanent hemostasis in 87% patients in group A and in 76% in group B (p = NS). Mortality was 6% in group A and 3% in group B. There were no differences between the two groups regarding requirements for emergency surgery, the number of transfusions, or the length of hospital stay. One patient in group B had a perforation. No other relevant complications were noted. In conclusion, combined therapy does not improve the results achieved with adrenaline alone.

Epinephrine↗