Can Helicobacter pylori eradication regimens be shortened in clinical practice? An open-label, randomized, pilot study of 4 and 7-day triple therapy with rabeprazole, high-dose levofloxacin, and tinidazole

BACKGROUND: Rabeprazole is a proton pump inhibitor which is particularly suitable for use in short-term Helicobacter pylori eradication treatment. Levofloxacin-based H. pylori eradication regimens have shown good efficacy and very few side effects. Shorter treatment and absence of significant side effects should improve compliance to therapy and increase the Hp H. pylori eradication rate. AIMS: To evaluate the effectiveness of 2 rabeprazole-based H. pylori eradication regimens in an open-label, randomized study carried out in a clinical practice setting. METHODS: One hundred sixty-nine consecutive, treatment-naive patients with H. pylori infection were randomized to receive rabeprazole (20 mg, bid), levofloxacin (500 mg, bid), and tinidazole (500 mg, bid) for either 4 [4-d rabeprazole, levofloxacin, tinidazole (RLT), n=85] or 7 days (7-d RLT, n=84). Before treatment, all patients underwent upper digestive endoscopy. Cure rates were assessed by means of C-urea breath test. and were compared with the eradication rate obtained with standard triple therapy in our Unit (ie, 78%) and average eradication rate reported in the literature (ie, 79%). RESULTS: The intention-to-treat eradication rates were 94% [87% to 98%, 95% confidence interval (CI)] and 95% (88% to 99%, 95% CI) in the 4-day RLT and 7-day RLT regimens, respectively, whereas per-protocol eradication rates were 95% (88% to 99%, 95% CI) in the 4-day RLT and 96% (90% to 99%, 95% CI) in the 7-day RLT. Both treatment regimens obtained significantly higher eradication rates as compared with standard triple therapy. The 4-day RLT showed significantly fewer side effects. CONCLUSIONS: In a clinical practice setting, both 4-day and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens achieved relevant H. pylori eradication rates in treatment-naive patients. The lower number of side effects makes the shorter treatment regimen preferable over the conventional 7-day treatment.     

Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C

Background/Aims: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, being a putative steatogenic factor, may promote liver fibrosis progression in patients with chronic hepatitis C. This study aimed to verify the role of recipient MTHFR polymorphism in favouring graft fibrosis progression in patients with recurrent HCV after orthotopic liver transplantation (OLT). Methods: We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method. Results: Recipients carrying the TT genotype had more frequently, 1‐year post‐OLT, homocysteine serum levels >23 μmol/L (P<0.05), serum triglycerides >180 mg/dL (P<0.02) and de novo diabetes mellitus (P<0.05) but not a higher frequency of graft steatosis. Time‐to‐event analysis in reaching an Ishak staging score >2 was performed by stratifying the recipients as follows: (a) patients with donor age ≤45 years, (b) patients with donor age >45 and C/^* genotype, and (c) patients with donor age >45 years and TT genotype. A significant linear trend was observed, with increasing frequencies as follows: (a) 8/37, (b) 10/19 and (c) 6/7 (P=0.0005). Conclusion: The MTHFR C677T polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C, in conjunction with donor age, but not via steatosis promotion.     

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance.Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function.In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents.A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.     

Surface-based multi-template automated hippocampal segmentation: Application to temporal lobe epilepsy

In drug-resistant temporal lobe epilepsy (TLE), detecting hippocampal atrophy on MRI is crucial as it allows defining the surgical target. In addition to atrophy, about 40% of patients present with malrotation, a developmental anomaly characterized by atypical morphologies of the hippocampus and collateral sulcus. We have recently shown that both atrophy and malrotation impact negatively the performance of volume-based techniques. Here, we propose a novel hippocampal segmentation algorithm (SurfMulti) that integrates deformable parametric surfaces, vertex-wise modeling of locoregional texture and shape, and multiple templates in a unified framework. To account for inter-subject variability, including shape variants, we used a library derived from a large database of healthy (n=80) and diseased (n=288) hippocampi. To quantify malrotation, we generated 3D models from manual hippocampal labels and automatically extracted collateral sulci. The accuracy of SurfMulti was evaluated relative to manual labeling and segmentation obtained through a single atlas-based algorithm (FreeSurfer) and a volume-based multi-template approach (Vol-multi) using the Dice similarity index and surface-based shape mapping, for which we computed vertex-wise displacement vectors between automated and manual segmentations. We then correlated segmentation accuracy with malrotation features and atrophy. SurfMulti outperformed FreeSurfer and Vol-multi, and achieved a level of accuracy in TLE patients (Dice=86.9%) virtually identical to healthy controls (Dice=87.5%). Vertex-wise shape mapping showed that SurfMulti had an excellent overlap with manual labels, with sub-millimeter precision. Its performance was not influenced by atrophy or malrotation (|r|<0.20, p>0.2), while FreeSurfer (|r|>0.35, p<0.0001) and Vol-multi (|r|>0.28, p<0.05) were hampered by both anomalies. The magnitude of atrophy detected using SurfMulti was the closest to manual volumetry (Cohen's d: manual=1.71, t=7.6; SurfMulti=1.60, t=7.0; Vol-multi=1.38, t=6.1; FreeSurfer=0.91, t=3.9). The high performance of SurfMulti regardless of cohort, atrophy and shape variants identifies this algorithm as a robust segmentation tool for hippocampal volumetry.     

Lesiones detectadas en el programa de cribado de cáncer colorrectal en el País Vasco: primera ronda 2009-2011

Colorectal cancer (CRC) is a major public health problem due to its incidence and mortality. In May 2008, the Basque Country approved the implementation of a population-based colorectal cancer screening program, using the immunochemical fecal occult blood test (FOBT), in persons aged 50-69 years. Patients with a positive result were invited to undergo colonoscopy with sedation.     

MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption

Background:  A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies.
Methods:  Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification.
Results:  Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p  < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years ( p  < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype ( p  = 0.002).
Conclusions:  The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC.     

Anomalous coronary circulation: left anterior descending and left circumflex coronary arteries arising from the right sinus of valsalva

Approximately 1% of adults who undergo cardiac catheterization have coronary anomalies. Patients may present with chest pain, arrhythmias, presyncope, and sometimes sudden cardiac death. Multidetector computed tomography (MDCT) is an excellent tool for identifying coronary artery anomalies and defining their course and relationship to the great vessels and surrounding structures; its value is incremental to conventional angiography. We present a rare case of a coronary anomaly involving three separate ostia at the right sinus of Valsalva for the left and right coronary vessels.     

Gram-negative osteomyelitis: clinical and microbiological profile

IntroductionDespite the growing interest in the study of Gram-negative bacilli (GNB) infections, very little information on osteomyelitis caused by GNB is available in the medical literature.Objectives and methods: To assess clinical and microbiological features of 101 cases of osteomyelitis caused by GNB alone, between January 2007 and January 2009, in a reference center for the treatment of high complexity traumas in the city of São Paulo.ResultsMost patients were men (63%), with median age of 42 years, affected by chronic osteomyelitis (43%) or acute osteomyelitis associated to open fractures (32%), the majority on the lower limbs (71%). The patients were treated with antibiotics as inpatients for 40 days (median) and for 99 days (median) in outpatient settings. After 6 months follow-up, the clinical remission rate was around 60%, relapse 19%, amputation 7%, and death 5%. Nine percent of cases were lost to follow-up. A total of 121 GNB was isolated from 101 clinical samples. The most frequently isolated pathogens were Enterobacter sp. (25%), Acinetobacter baumannii (21%) e Pseudomonas aeruginosa (20%). Susceptibility to carbapenems was about 100% for Enterobacter sp., 75% for Pseudomonas aeruginosa and 60% for Acinetobacter baumannii.ConclusionOsteomyelitis caused by GNB remains a serious therapeutic challenge, especially when associated to nonfermenting bacteria. We emphasize the need to consider these agents in diagnosed cases of osteomyelitis, so that an ideal antimicrobial treatment can be administered since the very beginning of the therapy.     

Assessment of prenatal exposure to ethanol by meconium analysis: results of an Italian multicenter study

Background: This study estimated in 7 Italian cities the prevalence of prenatal exposure to ethanol by determining fatty acid ethyl esters (FAEEs; palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, and arachidonic esters) and ethyl glucuronide (EtG) in neonatal meconium samples. Methods: A total of 607 meconium samples were obtained from neonatal wards of 7 public hospitals: Verona and San Daniele del Friuli in the northeast of the country, Reggio Emilia in the middle east, Florence and Rome in the center, and Naples and Crotone in the southwest of the peninsula. Meconium biomarkers were assessed by a validated methodology using liquid chromatography–tandem mass spectrometry and the results categorized using the accepted cutoff of 2 nmol/g total amount of 7 FAEEs and 2 nmol/g EtG, to differentiate between heavy maternal ethanol use during pregnancy and occasional or no use at all. Results: On the basis of the above‐reported cutoffs, the overall prevalence of newborns prenatally exposed to maternal ethanol was 7.9%: 0% in Verona, 4.0% in San Daniele del Friuli, 4.9% in Naples, 5.0% in Florence, 6.2% in Crotone, up to 10.6% in Reggio Emilia, and 29.4% in Rome. Low maternal education level and younger maternal age were associated with biomarker scores over the cutoff. There was also a significant correlation between the highest percentage of prenatal exposure in the capital and certain maternal sociodemographic characteristics. Conclusions: These results indicate considerable variability in the prevalence of fetal exposure to ethanol in different Italian cities, as determined by the objective measurement of biomarkers in meconium. These data, together with previous ones obtained in Barcelona, Spain, indicate that gestational ethanol exposure is widespread, at least in parts of Europe.     

A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis

By comparing untreated and dexamethasone-treated murine T cell hybridoma (3DO) cells by the differential display technique, we have cloned a new gene, GITR (glucocorticoid-induced tumor necrosis factor receptor family-related gene) encoding a new member of the tumor necrosis factor/nerve growth factor receptor family. GITR is a 228-amino acids type I transmembrane protein characterized by three cysteine pseudorepeats in the extracellular domain and similar to CD27 and 4-1BB in the intracellular domain. GITR resulted to be expressed in normal T lymphocytes from thymus, spleen, and lymph nodes, although no expression was detected in other nonlymphoid tissues, including brain, kidney, and liver. Furthermore, GITR expression was induced in T lymphocytes upon activation by anti-CD3 mAb, Con A, or phorbol 12-myristate 13-acetate plus Ca-ionophore treatment. The constitutive expression of a transfected GITR gene induced resistance to anti-CD3 mAb-induced apoptosis, whereas antisense GITR mRNA expression lead to increased sensitivity. The protection toward T cell receptor-induced apoptosis was specific, because other apoptotic signals (Fas triggering, dexamethasone treatment, or UV irradiation) were not modulated by GITR transfection. Thus, GITR is a new member of tumor necrosis factor/nerve growth factor receptor family involved in the regulation of T cell receptor-mediated cell death.