Solution-free and catalyst-free synthesis of ZnO-based nanostructured TCOs by PED and vapor phase growth techniques.

Zinc oxide (ZnO) is one of the most promising materials for realizing three-dimensional (3D) nanostructured transparent conducting oxides (TCOs) on large scale, because it is cheap, it can be modified with large concentrations of trivalent elements (such Al, Ga or In) and it is characterized by good electron mobility, wide bandgap and visible-range transparency. But, above all, it can be easily obtained in the form of different nanostructures with a large number of growth techniques. A solution-free and catalyst-free approach has been explored here by the vapor phase synthesis of vertically aligned ZnO nanorods on ZnO:Al (AZO) films grown by pulsed electron deposition (PED). The obtained nanostructured TCOs resulted to be homogeneous on large areas and easily patternable by means of mechanical masks. The morphology, crystalline structure, electrical and optical properties of the obtained samples have been characterized in depth. The possible use of such a nanostructured TCO in excitonic (e.g. DSSC) or low-reflectivity traditional solar cells is discussed.

Lack of association between porphyria cutanea tarda and alpha 1-antitrypsin deficiency.

OBJECTIVE: To determine whether alpha 1-antitrypsin deficiency is involved in the pathogenesis of chronic liver disease in patients with porphyria cutanea tarda and in their recently described high prevalence of hepatitis C virus infection. DESIGN: Consecutive patients diagnosed as having porphyria cutanea tarda and chronic liver disease. SETTING: A northern Italian hospital. METHODS: alpha 1-antitrypsin phenotypes were characterized by isoelectric focusing and the results confirmed by DNA analysis in 63 Italian patients with porphyria cutanea tarda. RESULTS: alpha 1-antitrypsin phenotypes different from the normal one were found in 13% of the patients. This prevalence did not differ from that in control subjects (9%). Clinical characteristics of patients with porphyria cutanea tarda with normal or altered alpha 1-antitrypsin phenotype, including age of presentation of the disease, prevalence of hepatitis C virus infection, liver histology, prevalence of iron overload and hepatocellular carcinoma occurrence, did not differ significantly. CONCLUSION: alpha 1-antitrypsin does not seem to play a role in the pathogenesis of chronic liver disease and hepatitis C virus infection in patients with porphyria cutanea tarda. Patients in whom the two defects coexist do not have a more severe disease.

Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study.

OBJECTIVE: After non-response to the initial course of therapy, retreatment with alpha-interferon is not effective. The aim of this study was to ascertain whether the administration of N-acetyl cysteine and vitamin E could increase the response rate to retreatment with alpha-interferon. DESIGN: Prospective, multicentre clinical trial. SETTING: Twelve hospitals in Lombardy, Italy. PARTICIPANTS: 120 consecutive patients affected by biopsy-proven chronic hepatitis C who had been non-responders to a previous course of alpha-interferon, administered at the dosage of 3-6 million units (MU) three times a week (tiw) for 6 months. INTERVENTIONS: The patients were randomly assigned to one of two groups of treatment: group A, natural interferon-alphaN3, 6 or 9 MU tiw, when the body weight was < 60 kg or > or = 60 kg, respectively; group B, the same dosage of natural interferon-alphaN3 in association with oral administration of N-acetyl cysteine 1200 mg/day and vitamin E 600 mg/day. The period of treatment was 6 months in both groups. RESULTS: Neither end-therapy biochemical response nor sustained biochemical response rates were improved by the combination treatment, and in no case was clearance of the virus from serum observed. CONCLUSIONS: In this randomized study carried out on 120 patients with chronic hepatitis C not responsive to alpha-interferon, oral supplementation with N-acetyl cysteine and vitamin E did not improve the poor efficacy of retreatment with alpha-interferon alone.

Spontaneous reporting of drug-related hepatic reactions from two Italian regions (Lombardy and Veneto).

BACKGROUND AND AIMS: Many currently used drugs are implicated in liver disorders ranging from asymptomatic abnormal liver function tests to fatal liver failure, and drug-induced hepatic reactions are the most frequent cause of the withdrawal of drugs from the market in the United States, United Kingdom and Spain. The aim of this study was to review the drug-induced hepatic reactions notified to the spontaneous surveillance system of two Italian regions (Lombardy and the Veneto) up to 31 December 1998. PATIENTS AND METHODS: The reports of hepatic adverse drug reactions were extracted from an inter-regional database of spontaneous adverse drug reaction reports and analysed by reporter category, patient age and sex, the underlying disease, the adverse reaction and drug exposure. In the case of drugs involved in more than four reports, a search was made of the Medline, Hepatox, Micromedex and WHO databases. RESULTS: Between 1988 and 1998, there were 310 reports of hepatic lesions associated with single drugs or fixed combinations, the most frequently involved patient categories being females and the elderly. Sixty percent of the reactions were classified as serious, with three fatal cases. Thirteen drugs were associated with more than four reports and accounted for 35% of all of the hepatic reactions. Six drugs not known as hepatotoxic agents were associated with hepatic reactions. CONCLUSIONS: In this study, spontaneous reports have suggested previously unknown hepatotoxicty of six drugs, and have improved drug safety profiles as shown in an Italian inter-regional health service.

Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study.

AIMS: To evaluate the prevalence, incidence and clinical relevance of bacterial infection in predominantly non-alcoholic cirrhotic patients hospitalised for decompensation. PATIENTS/METHODS: A total of 405 consecutive admissions in 361 patients (249 males and 112 females; 66 Child-Pugh class B and 295 class C) were analysed. Blood, urine, ascitic and pleural fluid cultures were performed within the first 24 hours, during hospitalisation whenever infection was suspected, and again before discharge. RESULTS: Over a one year period, 150 (34%) bacterial infections (89 community- and 61 hospital-acquired) involving urinary tract (41%), ascites (23%), blood (21%) and respiratory tract (17%) were diagnosed. The prevalence of bacterial peritonitis was 12%. Infections were asymptomatic in 69 cases (46%) and 130 (87%) involved a single site. Enteric flora accounted for 62% of infections, Escherichia Coli being the most frequent pathogen (25%). Community-acquired infections were associated with more advanced liver disease (Child-Pugh mean score 10.2+/-2.1 versus 9.5+/-1.9, p<0.05), renal failure (p<0.05), and high white blood cell count (p<0.01). Hospital-acquired infections occurred more frequently in patients admitted for gastrointestinal bleeding (p<0.05). The in-hospital mortality was significantly higher in infected than in non-infected patients (15% versus 7%, p<0.05), and infection emerged as an independent variable affecting survival. Moreover bacterial infection accounted for a significantly prolonged hospital stay. CONCLUSIONS: Bacterial infection, regardless of the aetiology, is a severe complication of decompensated cirrhosis, and, although frequently asymptomatic, accounts for both longer hospital stay and increased mortality.

[Surveillance of adverse reactions of drugs and monitoring of drug prescriptions as routine in hospital activities]. / La sorveglianza delle reazioni avverse da farmaci e il monitoraggio delle prescrizioni mediche come attività "normali" di reparti ospedalieri.

Since January 1988 is taking place a multicentre experience on pharmaco-epidemiology named ARIES (Adverse Reaction Identification Evaluation System), with two primary aims: surveillance of drug adverse reactions and monitoring of medical prescriptions. At present 5 departments of internal medicine are involved in the study. The factual cooperation of the departmental doctors depends on the evaluation of benefits and costs of the study. The benefits for doctor are: (a) the possibility of contributing to the research in a field which has not been systematically investigated in a hospital setting; b) the acquisition of skill in monitoring adverse reactions: to facilitate doctors cooperation an algorithm has been developed to select the events to be entered into the system; c) the possibility of evaluating and improving the prescription habits. At present, data on 9,000 patients and 60,000 prescriptions are available. As an example of utilization study, we report a research on antibiotics prescribed for bronchopneumonia in two departments involved in the ARIES project. The remarkable differences in the prescription settings lead to some rethinking on the strategies of such different prescription choices. In each department, the contribution of doctors is integrated by a monitor, entering additional information on drugs and patients into the system. Thanks to the cooperation of doctors and contribution of monitors, the pharmaco-epidemiology research may become a "normal" component of the hospital activities, thus allowing to systematically retrieve and process some basic knowledges, which are not routinely used, derived from the daily activity of the departmental doctor.

Ritodrine-related liver injury. Case reports and review of the literature.

beta-sympathicomimetic ritodrine chloridrate is a commonly used tocolytic agent for the treatment of preterm labour. Previous reports have described the occurrence of liver test abnormalities during ritodrine administration but the clinical significance and incidence of this side effect are still unclear. We report on two cases including one with a positive rechallenge of liver injury during oral ritodrine administration and a review of the literature.

Intravenous urography with iopamidol in children with reflux and obstructive nephropathy: effects on glomerular and tubular functions and the renin-angiotensin-aldosterone system.

Twenty-seven children [2 with chronic renal failure (CRF)] with reflux or obstructive nephropathy underwent intravenous urography with iopamidol 370, a nonionic contrast medium 1 (CM), osmolality 796 mosmol/kg, for renal growth evaluation. Mean iopamidol dosing was 1.69 ml/kg (range 1.22-2.42); the 2 children with CRF received 2 and 2.42 ml/kg respectively. One hour after infusion a significant decrease in haematocrit, haemoglobin, plasma sodium (Na+), chloride (Cl-), renin activity and aldosterone was observed, consistent with a possible plasma volume expansion due to the slightly hypertonic CM. At the same time there was a significant increase in fractional excretion of Na+, Cl- and potassium, probably due to the haemodynamic effects and tubular response to a substance acting as on osmotic diuretic. The -24 to +48 h monitoring of albuminuria, beta-2-microglobulin excretion, and in 4 children excretion of N-acetyl-beta-glucosaminidase and alanine-aminopeptidase did not show any relevant nephrotoxicity. No untoward effect of clinical relevance was observed.

Long-term administration of isosorbide-5-mononitrate does not impair renal function in cirrhotic patients.

Isosorbide-5-mononitrate (Is-5-Mn), alone or combined with beta-blockers, has been proposed for prophylaxis of variceal bleeding in cirrhosis. However, renal insufficiency, might be an important undesirable effect of this therapy, especially in patients with ascites. We assessed the changes in renal function induced in 26 cirrhotic patients by acute or chronic administration of Is-5-Mn. The acute administration of 20 mg of Is-5-Mn to 21 patients reduced mean blood pressure (83.4 +/- 2.4 vs. 92.8 +/- 3.4 mm Hg, P < .001), urine volume (5.5 +/- 0.8 vs. 8.7 +/- 1.1 mL/min, P < .05), urine sodium excretion (114 +/- 19 vs. 244 +/- 41 muEq/min, p < .001), urine potassium excretion (41 +/- 3.4 vs. 67 +/- 8.5 muEq/min, P < .001), and atrial natriuretic factor (74 +/- 10 vs. 98 +/- 12 pg/mL, P < .005). The glomerular filtration rate was decreased in the 11 patients with ascites (57 +/- 9 vs. 68 +/- 12 mL/min, P < .05), and plasma renin activity was increased in 4 ascitics. Twenty-one patients (16 from the acute study + 5 other patients) were given Is-5-Mn for 3 months at the dose of 80 mg/d. This did not affect blood pressure and renal function in patients without ascites, but reduced mean blood pressure (91.9 +/- 3.4 vs. 89.6 +/- 3 mm Hg, P < .05), urine volume (5.8 +/- 1.1 vs. 3.4 +/- 0.9 mL/min, P < .05), and urine sodium excretion (205 +/- 38 vs. 99 +/- 16 muEq/min, P < .01) in those with ascites. There were no changes in glomerular filtration rate and renal plasma flow, while plasma renin activity increased in only 3 patients with ascites and 1 without. Systemic hemodynamics and renal function of cirrhotic patients, especially those with ascites, are affected adversely by acute administration of Is-5-Mn. Long-term administration of the drug is well tolerated by compensated patients and does not affect renal plasma flow nor glomerular filtration rate, but can induce hypotension and sodium retention in patients with ascites.

Quantitative analysis of IgM anti-HBc in chronic hepatitis B patients using a new "gray-zone" for the evaluation of "borderline" values.

BACKGROUND/METHODS: In order to define the clinical significance of borderline levels of IgM anti-HBc in chronic hepatitis B patients, we followed up 89 untreated hepatitis B patients (19 HBeAg pos and 70 anti-HBe pos) for 1 year, with monthly monitoring of IgM anti-HBc using a highly sensitive quantitative microparticle enzyme immunoassay (IMx CORE-M, Abbott). As a control group we used 304 healthy subjects: 150 HBsAg negative and anti-HBc/anti-HBs positive, and 154 without markers of HBV infection. The statistical analysis performed by Receiver Operating Characteristic curve indicated the 100% sensitivity cut-off at 0.081 IMx index and 100% specificity cut-off at 0.358 IMx index. RESULTS: We could define the range of a chronic hepatitis B "gray-zone" between 0.100 [80.6% specificity (95% CI, 76.2%-85%), 96.6% sensitivity (95% CI, 92.8%-100%)] and 0.200 [95.7% specificity (95% CI, 93.4%-98%) and 78.7% sensitivity (95% CI, 70.2%-87.2%)] of the IgM anti-HBc-IMx index. In fact, none of the chronic hepatitis B patients had IgM anti-HBc-IMx values persistently below 0.100 during the follow-up, whereas 57.3% had values persistently higher than 0.200. In 38.2%, IgM anti-HBc values occasionally fell within the "gray-zone" limits. In the remaining four patients (4.4%), the results overlapped the "gray-zone" values. CONCLUSIONS: These results suggest that the use of a chronic hepatitis B "gray-zone" for values of quantitative IgM anti-HBc assays helps to distinguish "true healthy carriers" from asymptomatic chronic anti-HBe positive hepatitis B patients who have been shown to have temporary remissions of liver disease and frequently undetectable serum HBV-DNA.

No association between genetic hemochromatosis and alpha1-antitrypsin deficiency.

Genetic hemochromatosis and alpha1-antitrypsin (AAT) deficiency are frequent in white populations. Conflicting data on the association of the two conditions and on the severity of the disease in those in whom these disorders coexist have emerged from analyses of small numbers of patients. To determine if the frequency of AAT deficiency is increased in genetic hemochromatosis, we characterized this protein by isoelectric focusing and DNA analysis in 115 Italian patients with the disease and 290 controls. The frequency of AAT deficiency in patients with genetic hemochromatosis was similar to that in controls (10% and 9%, respectively). The prevalence of cirrhosis in patients with genetic hemochromatosis with MM phenotype was 53%, compared with 58% in those with non-MM phenotype; that of hepatocellular carcinoma, occurring only in cirrhotic patients, was 22% and 28%, respectively. In conclusion, the frequency of AAT deficiency was not increased in our large series of Italian patients with genetic hemochromatosis. Patients in whom the two defects coexisted did not appear to have a more severe disease, but the limited number of subjects with non-MM phenotype does not allow a conclusive evaluation of clinical differences between them and patients with genetic hemochromatosis with MM phenotype.

Prediction of relapse or sustained response in biochemical responders by serum hepatitis C virus RNA monitoring during interferon therapy.

Normalization of serum aminotransferase levels is achieved in approximately 50% of chronic hepatitis C patients treated with interferon (IFN); however, in about one-half of these patients the hepatitis relapses after therapy. In this study we investigated the efficacy of serum hepatitis C virus (HCV) RNA monitoring during IFN therapy to predict the outcome of a biochemical end-of-treatment (ETR) response. Eighty patients with chronic hepatitis C received leucocyte (natural) IFN-alpha (13 patients) or recombinant IFN-alpha2a (67 patients). Antiviral therapy was given for 12 months to 43 (53.7%) responders and this group was analysed further. During follow-up, 15 relapsed and 28 showed a sustained response (median follow-up 50 months, range 39-67 months). Viraemia was monitored at baseline, and at months 1, 3, 6, 9 and 12 of treatment, by nested polymerase chain reaction (PCR) (sensitivity 10-100 copies ml-1). A combination of positive nested PCR and HCV RNA values at the 3rd and 6th months of treatment was 100% predictive of relapse (sensitivity, 66.6%; specificity, 100%). A combination of negative nested PCR and HCV RNA values at the 1st and 3rd months of treatment was 100% predictive of sustained response (sensitivity, 39.3%; specificity, 100%). In conclusion, serum HCV RNA monitoring is an appropriate and reliable tool for predicting early outcome of the biochemical ETR response after IFN discontinuation. This could be useful in the modulation of therapeutic management of chronic hepatitis C.