Ferrous Iron Under Oxygen-Rich Conditions in the Deep Mantle.

Recent experiments have demonstrated the existence of previously unknown iron oxides at high pressure and temperature including newly discovered pyrite-type FeO2 and FeO2Hx phases stable at deep terrestrial lower mantle pressures and temperatures. In the present study, we probed the iron oxidation state in high-pressure transformation products of Fe3+OOH goethite by in situ X-ray absorption spectroscopy in laser-heated diamond-anvil cell. At pressures and temperatures of ~91 GPa and 1,500-2,350 K, respectively, that is, in the previously reported stability field of FeO2Hx, a measured shift of -3.3 ± 0.1 eV of the Fe K-edge demonstrates that iron has turned from Fe3+ to Fe2+. We interpret this reductive valence change of iron by a concomitant oxidation of oxygen atoms from O2- to O-, in agreement with previous suggestions based on the structures of pyrite-type FeO2 and FeO2Hx phases. Such peculiar chemistry could drastically change our view of crystal chemistry in deep planetary interiors.

The Fe-FeSi phase diagram at Mercury's core conditions.

Mercury's metallic core is expected to have formed under highly reducing conditions, resulting in the presence of significant quantities of silicon alloyed to iron. Here we present the phase diagram of the Fe-FeSi system, reconstructed from in situ X-ray diffraction measurements at pressure and temperature conditions spanning over those expected for Mercury's core, and ex situ chemical analysis of recovered samples. Under high pressure, we do not observe a miscibility gap between the cubic fcc and B2 structures, but rather the formation of a re-entrant bcc phase at temperatures close to melting. Upon melting, the investigated alloys are observed to evolve towards two distinct Fe-rich and Fe-poor liquid compositions at pressures below 35-38 GPa. The evolution of the phase diagram with pressure and temperature prescribes a range of possible core crystallization regimes, with strong dependence on the Si abundance of the core.

Clinical trial: comparison of weekly once versus twice half-dose weekly administration of pegylated interferon alpha 2b in combination with ribavirin for the treatment of HCV-1 positive patients with chronic hepatitis C.

BACKGROUND: Pegylated interferon (PEG-IFN) alpha2b is currently used as a once weekly injection in combination with ribavirin for the treatment of chronic hepatitis C. AIM: To test whether twice half-dose weekly administration may improve the virological response in difficult-to-treat hepatitis C virus-1 patients. METHODS: Thirty patients were treated with 1.5 microg/kg of PEG-IFN alpha2b given once weekly for 48 weeks (group A) and were compared with 30 patients treated with the same dose of PEG-IFN alpha2b divided in twice weekly doses of 0.75 microg/kg for the initial 4 weeks (group B). All patients were hepatitis C virus-1 positive and received weight-based ribavirin (800-1400 mg/daily). RESULTS: Weekly twice half-dose administration of PEG-IFN alpha2b for the first 4 weeks was associated with lower rates of biochemical and virological response at all time points compared with a once weekly schedule, and with significantly higher rates of in-therapy breakthrough leading to significantly lower rates of end of therapy response (week 48). The rate of sustained virological response was of 56.7% in group A and 36.7% in group B. CONCLUSIONS: Weekly twice half-dose administration of PEG-IFN alpha2b is not superior to the standard once weekly schedule, and might be less efficacious.

Natural history of initially mild chronic hepatitis C.

The hepatitis C virus is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in western countries. Chronic hepatitis C is highly heterogeneous and many patients present with a mild form of liver disease. Population-based studies have indeed demonstrated that around 50% of hepatitis C virus carriers have persistently normal ALT and two-third have mild histological liver lesions. Studies on the natural history of initially mild chronic disease indicate that the short-term outcome is always benign. However, progression of liver fibrosis can be observed at long-term (>5-7 years) follow-up, particularly in those cases who have elevated and/or fluctuating transaminase levels. Observational prospective studies and outcome modelling projections indicate that the risk of liver disease progression towards severe fibrosis/cirrhosis is minimal at 10-15 years in hepatitis C virus carriers with persistently normal ALT, around 5-10% in patients with elevated ALT and F0 (no fibrosis) in the initial biopsy but >30-40% in chronic carriers with elevated ALT and F1 (portal fibrosis) in the initial biopsy. Cofactors like age at infection, alcohol, coinfections and liver steatosis accelerate disease progression. On the basis of these findings, patients with initially mild chronic hepatitis C and elevated ALT should be proposed for antiviral therapy in the absence of contraindications.

[Perinatal listeriosis. Apropos of two cases]. / Listeriosi perinatale. A proposito di due casi.

Two cases of perinatal listeriosis are reported by the Authors. The Authors emphasize that in Italy the incidence of this disease is undervalued. Additionally, the pregnant woman comes to be affected by forms which do not clinically fall within standard levels and whose course does not get worse over a certain limit. On the other hand, the fetus suffers substantial damages like abortion, premature labour with its subsequent failure or in case with a fetus affected by listeriosis. Two main clinical forms do exist in the neonatal period: the early form that is the septicemic form and the later form that is the meningitic form. As regards therapy on newborn, the Authors report that a mixture of Ampicillin and Aminoglycosides turns out to be successful for recovering patients from listeriosis. Furthermore, the Ampicillin together with a general igienic therapy are a good protection for the fetus and newborn in a pregnant woman.

Fibrosis progression in initially mild chronic hepatitis C.

The natural history of chronic hepatitis C presenting with no/minimal liver fibrosis is uncertain with controversies on risk of progression and need for antiviral treatment. We studied rates and determinants of fibrosis progression in initially mild chronic hepatitis C. One hundred and six patients (mean age 41.65 +/- 12.83 years) with chronic hepatitis C virus infection and no/minimal fibrosis in the initial liver biopsy (F0/F1 by METAVIR score) were followed prospectively while untreated with repeated biopsy after 5 or more years (mean interval 7.8 +/- 1.51 years). Patients showing fibrosis progression were compared with nonprogressors for baseline and follow-up parameters. Sixty-four patients (60.4%) showed fibrosis progression including 13 of 27 (49%) with F0 and 51 of 79 (65%) with F1. Progression to F3 or cirrhosis was seen in 36% of those with F1 initially. Fibrosis progression (DeltaF/year) was associated with age (P < 0.0001), baseline and follow-up alanine aminotransferase (ALT) (P = 0.005), histological activity (P = 0.004) and steatosis (P = 0.002) in the initial biopsy and use of alcohol (P = 0.008). Thus liver fibrosis progression occurs in two-thirds of patients with initially mild chronic hepatitis C within 5-10 years and advanced fibrosis/cirrhosis develops in one-third of those with F1 initially. Fibrosis is facilitated by older age and alcohol and associated with inflammatory activity and ALT levels. Antiviral therapy should be considered in mild chronic hepatitis C.

Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications.

BACKGROUND AND AIMS: The natural history of initially compensated cirrhosis due to hepatitis B (HBV) or hepatitis C (HCV) virus is only partially defined. We have investigated morbidity and mortality rates and the hierarchy of complications in compensated viral cirrhosis over a long follow up period. PATIENTS AND METHODS: A cohort of Italian patients with initially compensated cirrhosis of viral aetiology were followed up at six monthly intervals with laboratory tests to identify major complications (ascites, gastrointestinal bleeding, portal-systemic encephalopathy, hepatocellular carcinoma) and to assess the progression of Child's stage and mortality rate due to liver related causes. RESULTS: Between 1986 and 1996, 312 patients (43 HBV positive, 254 HCV positive, and 15 HBV and HCV coinfected) were included. During a median follow up of 93 (range 14-194) months, 102 (32.6%) patients developed at least one complication (HCV positive 31.1%; HBV positive 34.8%; HBV and HCV coinfected 53.3%). Overall, the most frequent complication was hepatocellular carcinoma which occurred in 65 (20.8%) cases, followed by ascites (61 cases, 19.5%), gastrointestinal bleeding (14 cases, 4.5%), and portal-systemic encephalopathy (six cases, 1.9%). Progression of Child's stage was observed in 62 patients (19.8%). Death from liver disease occurred in 58 (18.6%) cases and in 70.7% this was due to hepatocellular carcinoma. Hepatocellular carcinoma was the first complication to develop in 59 cases and represented the most frequent first complication in both HCV and HBV/ HCV related cirrhosis. CONCLUSIONS: These results indicate significant morbidity and mortality during the first decade after diagnosis of compensated cirrhosis due to HBV and/or HCV, and identify hepatocellular carcinoma as the most frequent and life threatening complication, particularly in HCV positive cases.

Natural course of subclinical hypothyroidism in Down's syndrome: prospective study results and therapeutic considerations.

Pathogenesis, natural course and therapeutic management of subclinical hypothyroidism (SH) in Down's syndrome (DS) remain object of debate in literature. In the present study thyroid function, antithyroid antibody (ATA) prevalence and serum lipid concentrations were investigated in a group of 344 Down patients (DP) and data were compared with those obtained from a control group of 257 age and sex matched healthy subjects. Thyroid function and ATA prevalence were also studied in 120 parents of DP. SH prevalence was clearly higher in DP (32.5% of cases) than in controls (1.1%) and parents (0%). Similarly, ATA prevalence was higher in DP (18% of cases) than in controls (5.8%) and parents (6.6%). In spite of this, no correlation was found in DP between SH and ATA prevalences, since ATA were detected in 18.7% of SH-DP and in 15.8% of euthyroid DP. Thus, circulating ATA were not detected in the majority of SH-DP. No significant differences regarding T4, FT4, T3 and serum lipid levels among SH and euthyroid DP and controls were found. Moreover, TSH levels were only slightly increased, generally less than 10 microU/ml, in most cases of SH-DP. Follow-up was longer than 24 months (range 2-7 years, mean 3.1) in a group of 201 DP: two different patterns of SH course were observed, mainly depending on the presence or the absence of circulating ATA. In particular, 35.7% of ATA-positive SH-DP developed a clinically evident thyroid disease (overt hypothyroidism or hyperthyroidism), while no similar case was recorded among ATA-negative SH-DP.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of thrice weekly vs daily human leucocyte interferon-alpha therapy for chronic hepatitis C. TVVH Study Group.

Standard treatment for chronic hepatitis C currently consists of 3-6 million units (MU) of interferon-alpha (IFN-alpha) given thrice weekly (t.i.w.) for 12 months, obtaining rates of sustained response (SR) that usually do not exceed 15-25%. Some recent reports have suggested that daily administration of IFN-alpha may be more efficacious. More than 7 years ago, when standard therapy for hepatitis C was usually given for 6 months, we conducted a randomized clinical trial comparing daily vs t.i.w. treatment. In this study, 149 patients with chronic hepatitis C were randomized to received 3 MU of IFN-alpha either t.i.w. for 6 months or daily for 3 months followed by t.i.w. for 3 months. All patients were treated with human leucocyte IFN-alpha and were followed-up for up to 72 months after inclusion. Overall, patients treated daily or t.i.w. had similar rates of virological response after 3 months of induction [24/49 (50%) vs 40/100 (40%)], at the end of therapy [15/49 (31%) vs 36/100 (36%)] and at the end of follow-up [6/49 (12%) vs 9/100 (9%)]. However, when patients infected with HCV types other than HCV-1 were studied, there was a trend favouring the daily schedule that was associated with a higher [5/20 (25%) vs 5/48 (10%)] rate of long-term SR. All patients with a virological response - hepatitis C virus (HCV) RNA negative in serum as determined using the polymerase chain reaction - at 6 months after therapy remained in biochemical and virological remission at long-term follow-up, while seven of eight subjects who had normal alanine aminotransferase (ALT) levels but were serum positive for HCV RNA at 6 months, relapsed later, indicating that serum HCV RNA is better than ALT at predicting long-term cure after IFN-alpha therapy in chronic hepatitis C.