Use of lactoferrin for Helicobacter pylori eradication. Preliminary results

BACKGROUND: One-week triple therapy is the most frequently recommended treatment of Helicobacter pylori infection. The associated eradication rate is satisfactory; nevertheless, it is advisable to look for more effective therapies. Our aim was to test the efficacy of a standard triple therapy plus bovine lactoferrin for the eradication of H. pylori infection. STUDY: This open, randomized, single-center study was designed to include 150 consecutive H. pylori-positive patients with dyspeptic symptoms and gastritis who received triple therapy with rabeprazole, clarithromycin, and tinidazole plus lactoferrin for 7 days (group A), rabeprazole, clarithromycin, and tinidazole for 7 days (group B), or rabeprazole, clarithromycin, and tinidazole for 10 days (group C). H. pylori status was assessed 8 weeks after the end of treatment by means of the 13C-urea breath test or H. pylori stool antigen test. RESULTS: The 7-day treatment including lactoferrin (group A) was successful in 100% (24/24) of the patients. The eradication rates in groups B and C were 76.9% (20/26 patients; 95% CI, 61%-93%) and 70.8% (17/24 patients; 95% CI, 53%-89%), respectively. A significant difference was found between group A and group B (P = 0.023) and group A and group C (P = 0.022). No differences were found between group B and group C (P = 1.00). CONCLUSION: These results suggest that lactoferrin could be a new, effective agent when added to antimicrobial therapy for the eradication of H. pylori. This treatment schedule could be proposed for larger trials of H. pylori eradication therapy, focusing on the excellent preliminary cure rate, good compliance to the treatment schedule, and relatively low price of lactoferrin for full treatment.     

Insulin resistance is associated with liver fibrosis in non-diabetic chronic hepatitis C patients

BACKGROUND/AIMS: Liver steatosis is a frequent finding in chronic hepatitis C. An association has been suggested between steatosis and fibrosis progression rate, but the pathogenetic mechanisms linking fatty infiltration and collagen deposition are unknown. METHODS: We measured the levels of insulin resistance (as HOMA score) and leptin in 221 non-diabetic chronic hepatitis C patients, to assess their impact on liver steatosis and fibrosis, relative to other factors, using a multivariable logistic regression. RESULTS: When all 221 patients were considered, steatosis was associated with excessive alcohol intake, genotype 3, and serum HCV RNA level, whereas fibrosis was associated with HOMA score and age. In 152 patients infected with genotype non-3, steatosis was associated with alcohol abuse and HCV RNA level, and fibrosis with HOMA score and age. In the 69 patients with genotype 3, steatosis and fibrosis were associated with each other. The association between fibrosis and HOMA score held also when 22 obese patients were excluded from the analysis. Levels of insulin resistance were not correlated with the presence of steatosis. CONCLUSIONS: Thus, insulin resistance (but not leptin) may play a role in fibrogenesis in chronic hepatitis C patients infected with genotype non-3.     

Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients

Our objective was to construct and validate a Multidimensional Prognostic Index (MPI) for 1-year mortality from a Comprehensive Geriatric Assessment (CGA) routinely carried out in elderly patients in a geriatric acute ward. The CGA included clinical, cognitive, functional, nutritional, and social parameters and was carried out using six standardized scales and information on medications and social support network, for a total of 63 items in eight domains. A MPI was developed from CGA data by aggregating the total scores of the eight domains and expressing it as a score from 0 to 1. Three grades of MPI were identified: low risk, 0.0-0.33; moderate risk, 0.34-0.66; and severe risk, 0.67-1.0. Using the proportional hazard models, we studied the predictive value of the MPI for all causes of mortality over a 12-month follow-up period. MPI was then validated in a different cohort of consecutively hospitalized patients. The development cohort included 838 and the validation cohort 857 elderly hospitalized patients. Of the patients in the two cohorts, 53.3 and 54.9% were classified in the low-risk group, respectively (MPI mean value, 0.18 +/- 0.09 and 0.18 +/- 0.09); 31.2 and 30.6% in the moderate-risk group (0.48 +/- 0.09 and 0.49 +/- 0.09); 15.4 and 14.2% in the severe-risk group (0.77 +/- 0.08 and 0.75 +/- 0.07). In both cohorts, higher MPI scores were significantly associated with older age (p = 0.0001), female sex (p = 0.0001), lower educational level (p = 0.0001), and higher mortality (p = 0.0001). In both cohorts, a close agreement was found between the estimated mortality and the observed mortality after both 6 months and 1 year of follow-up. The discrimination of the MPI was also good, with a ROC area of 0.751 (95%CI, 0.70-0.80) at 6 months and 0.751 (95%CI, 0.71-0.80) at 1 year of follow-up. We conclude that this MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients into groups at varying risk of mortality.     

Correlates of HIV-1 shedding in cervicovaginal secretions and effects of antiretroviral therapies

OBJECTIVES: To evaluate the determinants of HIV-1 RNA shedding in cervicovaginal secretions and the effects of antiretroviral therapy in a group of infected women. METHODS: A total of 122 women from whom paired peripheral blood and cervicovaginal lavage samples were available were enrolled in the study. HIV-1 RNA was quantified in the plasma and cell-free fraction of cervicovaginal lavages by the nucleic acid sequence-based amplification assay (lower limit of detection 80 copies/ml). RESULTS: Seventy-one per cent of the women had detectable viral load in the cervicovaginal lavage and this appeared to be correlated to plasma viral load and to the degree of immunodeficiency as expressed by the absolute number of CD4 cells. Antiretroviral-treated patients had a lower risk of shedding the virus in the genital tract, but this association was limited to patients treated with highly active antiretroviral therapy (HAART). However, in 25% of women with undetectable plasma viral load, a genital shedding of the virus was demonstrated. CONCLUSION: Plasma viral load may fail as a marker of infectivity of genital secretions. HAART treatment seems to be more efficacious in suppressing viral shedding at the genital level. The female genital tract represents a distinct compartment for HIV-1 replication/evolution.     

Natural Course of Functional Dyspepsia After <Emphasis Type="Italic">Helicobacter pylori</Emphasis>Eradication: A Seven-Year Survey

The role of Helicobacter pylori(Hp) in functional dyspepsia (FD) is controversial and previously published data do not help to clarify whether Hp eradication affects the natural course of FD. The aim of this study was to assess the clinical course of FD during a long follow-up period of 7 years in a homogeneous sample of Hp-eradicated patients. Among patients referred between 1991 and 1996, patients with FD and infected with Hp were enrolled. Patients were administered a structured symptom questionnaire and evaluated after Hp eradication at each 12-month time points. Patients were divided into three FD subgroups: predominantly ulcer-like, dismotility-like, and reflux-like symptom clusters. A composite symptom score ranging from 0 (no symptom) to 3 (severe symptoms) was assigned to each FD cluster. Of the 1685 screened patients, 405 had FD and 211 of them (52.1%) were also Hp-positive. During the follow-up, the amount of missing information varied from 10% to 17.5% within the first 6 years and was 30.8% at 7 years. The rates of improved patients ranged from 33% (reflux-like) to 34.9% (dismotility-like) to 47.3% (ulcer-like). However, only a proportion of 10%–50% of them was symptom-free after eradication and also at each 12-month evaluation, whereas the other patients became symptomatic at different times. FD symptoms slightly improve after Hp eradication over a long period of time but a large percentage of these improved patients may experience FD symptoms again, even after some years of well-being after Hp eradication. This study was not supported by any pharmaceutical company, government agency, or other grants: under the auspices of Roberto Farini Foundation for Gastroenterological Research. The data were analyzed by G. Leandro, MD. Preliminary versions of this paper were presented in abstract form at the 16th International Workshop of Gastrointestinal Pathology and Helicobacter, September 3–6, 2003, Stockholm Sweden; the 11th United European Gastroenterology Week, November 1–5, 2003, Madrid, Spain; the 10th National Congress on Digestive Diseases, March 27–31, 2004, Torino, Italy; and Digestive Disease Week, May 15–20, 2004, New Orleans, Louisiana, USA.     

Effect of Acute and Chronic Cimetidine Administration on Acetaminophen Metabolism in Humans

In our study of the effect of acute cimetidine administration on acetaminophen metabolism, 10 healthy subjects were given an oral dose of acetaminophen (1 g) before and after administration of cimetidine (800 mg, po). In another experiment, 10 patients with duodenal ulcer received acetaminophen (1 g, po) before and after 2 months of cimetidine treatment (400 mg twice a day, po). Acetaminophen metabolism in blood and urine was studied for 9 h in each experiment. The half-life of acetaminophen was similar either in the absence or presence of both acute and chronic cimetidine administration. Although acute cimetidine ingestion did not affect acetaminophen urinary excretion, prolonged cimetidine treatment resulted in a slight but significant decrease of acetaminophen mercapturate urinary excretion. These findings suggest that, unlike acute cimetidine, prolonged histamine H2 antagonist therapy inhibits acetaminophen oxidation to its reactive metabolite. The clinical relevance of such an interaction remains to be explored.     

Thromboelastography with citrated blood: comparability with native blood, stability of citrate storage and effect of repeated sampling.

Thromboelastography (TEG) with recalcified citrate blood is used as an alternative to native blood, but there is insufficient data regarding sample reliability and stability over time. Thus, TEG parameters of freshly drawn native blood were compared with those of recalcified citrated blood without celite in 10 healthy subjects, and the effect of repeated sampling over 240-min storage was evaluated. All TEG parameters following citrate storage remained stable between 30 min [clot formation time (k) = 7.2 +/- 0.6 min; maximum amplitude (ma) = 48.5 +/- 1.9 mm] and 2 h (k = 7.1 +/- 0.6 min; ma = 46.2 +/- 2.5 mm) after initial sampling, but were not comparable with native blood (k = 9.3 +/- 0.7 min; ma = 43.5 +/- 2.5 mm) at any time point. TEG parameters of repeatedly sampled citrated blood had a significant overall hypercoagulable trend throughout 4 h following sampling. In conclusion, in order to achieve reproducible results, citrated blood without celite may be utilized between 30 min and 2 h following sampling, but in normal subjects the TEG parameters following citrate storage are not comparable with native blood, possibly because of incomplete inhibition of the activation of the coagulation cascade. Thus, citrated blood can be used as a surrogate of native blood in assessing coagulation using TEG, but if repeated sampling is used the trend in hypercoagulability must be considered.