Commensurate germanium light emitters in silicon-on-insulator photonic crystal slabs.

We report on the fabrication and characterization of silicon-on-insulator (SOI) photonic crystal slabs (PCS) with commensurately embedded germanium quantum dot (QD) emitters for near-infrared light emission. Substrate pre-patterning defines preferential nucleation sites for the self-assembly of Ge QDs during epitaxial growth. Aligned two-dimensional photonic crystal slabs are then etched into the SOI layer. QD ordering enhances the photoluminescence output as compared to PCSs with randomly embedded QDs. Rigorously coupled wave analysis shows that coupling of the QD emitters to leaky modes of the PCS can be tuned via their location within the unit cell of the PCS.

Excitation Intensity Driven PL Shifts of SiGe Islands on Patterned and Planar Si(001) Substrates: Evidence for Ge-rich Dots in Islands.

For randomly nucleated SiGe/Si(001) islands, a significantly stronger blue-shift of the PL spectra as a function of the excitation intensity is observed when compared to islands grown on patterned substrates side by side within the same run in a solid source molecular beam epitaxy chamber. We ascribe this different PL behavior to the much larger inhomogeneity of the Ge distribution in islands on planar substrates when compared to islands grown on pit-patterned ones, as observed previously. 3D band-structure calculations show that Ge-rich inclusions of approximately 5 nm diameter at the apex of the islands can account for the observed differences in the PL spectra. The existence of such inclusions can be regarded as a quantum dot in an island and is in agreement with recent nano-tomography experiments.

Isoprostanes as markers of oxidative stress-induced cell damage in porcine islet cell isolation.

INTRODUCTION: Mechanical stress and reagents used during the isolation and purification process as well as digestion time and temperature can alter the success of porcine islet cell (PIC) isolation. This study aimed to characterize the occurrence of isoprostanes during PIC isolation using a modified automated Ricordi method and to evaluate their influence on PIC isolation outcome. METHODS: Porcine pancreatic tissue was harvested at the local slaughter house, and 10 PIC isolations were performed using a modified automated Ricordi method. As positive controls for tissue damage-associated oxidative stress, six consecutive PIC isolations were performed in the presence of 1 mug lipopolysaccharide (LPS). PIC were purified by density gradient centrifugation using the Lymphoprep density gradient. Isoprostane measurement was performed using enzyme-linked immunosorbent assay. RESULTS: The final yield of viable and pure PICs in the experimental group was 3479 +/- 542 IEQ/g pancreas, and the LPS group yielded lower cell numbers compared to the experimental group. Isoprostane levels were significantly elevated in the LPS group as compared to the experimental group at all time points during the isolation from the beginning of the digestion process. DISCUSSION: PIC isolation and purification results significantly differed in the two experimental groups, underlining the negative effects of oxidative stress on PIC viability and purity, which impact negatively on PIC transplantation success.

Preoxygenation of different preservation solutions for porcine pancreas preservation.

INTRODUCTION: Organ preservation quality impacts porcine islet cell isolation and transplantation success. Among several preservation methods, the two-layer method is promising, but technically demanding and fails to deliver sufficient oxygen. The use of hyperbaric oxygenation may be an easier, more effective method to supply high partial pressure of oxygen (pO(2)) for organ storage. Therefore, the aim of this study was to test the capability of preoxygenation of various preservation solutions with HBO to maintain high pO(2) levels. METHODS: University of Wisconsin (UW), Custodiol, Perfadex, or Celsior solutions were preoxygenated in a pressure chamber. NaCl served as the control. pO(2) levels were measured at defined times. The oxygen storage capability was evaluated by leaving the storage bottles open for 2 minutes. RESULTS: It was feasible to preoxygenate preservation solutions. The best solution to maintain high pO(2) tensions was Perfadex, followed by Celsior, and UW. DISCUSSION: The greater the amount of oxygen in the preservation solution, the more oxygen can be delivered to the preserved pancreas. Further studies on the influence of preoxygenated preservation solutions on the porcine pancreas are warranted to improve organ quality, porcine islet cell isolation, and transplantation success.

Chronic hepatitis C in Austria, 1992-2006: genotype distribution and demographic factors.

Chronic hepatitis C is a leading cause of end-stage liver disease and, with a worldwide prevalence of up to 3%, is a pandemic infectious disease. Austria, like most western European countries can be considered as a low prevalence country. This analysis aimed to assess the distribution of hepatitis C virus (HCV) genotypes in patients with chronic HCV infection in Upper Austria. Between September 1992 and December 2006, we identified 1,318 consecutive patients who tested positive for HCV RNA. Genotyping was routinely performed in 1,239 of the 1,318 patients, and in a subgroup of 617 patients data on the source of transmission were collected. Additionally we obtained data on liver histology and body mass index in a subsample of 273 of the 617 patients. Hepatitis C genotypes 1, 2, 3, 4, 6 and co-infections were found in 80.4%, 4.5%, 12.3%, 2.7%, 0.1% and 0.2% of the patients, respectively. There was a highly significant age difference in relation to gender at the time of diagnosis of chronic hepatitis C, with women being older than men (men: 45.0 years; women: 49.3 years; p<0.0001). The number of new cases of chronic hepatitis C decreased substantially over the last decade, but although risk factors for obtaining HCV are well established, we did not find a decrease in the age of first diagnosis. Besides consistent screening in defined risk groups it is important to raise awareness for risk factors for HCV acquisition and liver disease progression.

Ductal injection of University of Wisconsin solution prior to pancreas preservation prevents oxidative cell damage.

INTRODUCTION: Several studies have been carried out investigating different preservation methods and preservation solutions for the pancreata of various species. Attention has to be drawn to the extreme vulnerability of porcine pancreata (PP) to oxidative stress due to the lack of endogenous antioxidants. This study sought to evaluate the influence of cannulation and infusion of different volumes of University of Wisconsin (UW) solution immediately after organ retrieval on PP organ quality. METHODS: PP from 24 slaughterhouse pigs were harvested with immediate cannulation of the pancreatic duct for infusion of 10 mL, 20 mL, 50 mL, or 100 mL UW solution. The organs were stored in cold UW solution. Control organs were only stored in UW. After 6 hours of cold ischemia, tissue and supernate samples were analyzed for markers of oxidative cell damage, adenosine triphosphate (ATP) levels, and occurrence of apoptosis. RESULTS: The fewest apoptotic cells were detected in the PP infused with 50 mL UW via the pancreatic duct (PP 50) as compared with all other groups. Oxidative cell damage was lowest and ATP levels were highest in the PP 50 group. DISCUSSION: Because PP 50 showed significantly better results when compared with all other groups, we suggest that infusion of 50 mL UW via the pancreatic duct immediately after organ retrieval may be useful to minimize oxidative cell damage and cell death in PP.

Early viral kinetics on treatment with pegylated interferon-alpha-2a in chronic hepatitis C virus genotype 1 infection.

Even with pegylated (PEG) interferons (IFN), therapy of chronic hepatitis C (genotype 1) remains unsatisfactory. The initial viral response to IFN identifies patients infected with IFN resistant viruses not responding to standard IFN/ribavirin therapy. The impact of primary IFN unresponsiveness for PEG-IFN-alpha-2a/ribavirin therapy is unknown. Viral load was measured in 22 chronic hepatitis C (genotype 1) patients before and 24 h after 9 MU IFN-alpha-2a (days 0 and 1), and before and during weekly 180 microg PEG-IFN-alpha-2a (days 7, 8, 11, 14 and 21) administration. Thereafter, ribavirin (800 mg/d) was added for 6 months. Virological responders continued treatment for a further 6 months. Twenty-eight patients treated with standard IFN/ribavirin therapy in a previous study using an analogous protocol served as historic controls. After 6 months 15 (68.2%) patients were (HCV-RNA) negative, eight of whom (36.4%) had a sustained response. The decrease in viral load 24 h after 9 MU IFN-alpha-2a was greater in virological responders (1.05 log [0.25-1.67]) than in nonresponders (NR) (0.34 [0.14-0.65]; P=0.003). In contrast, viral decline was not different between responders and NRs during the first 2 weeks on PEG-IFN-alpha-2a. All patients with an initial decline > 1.4 log became sustained responders. Five of 12 patients with a log change < 0.8 became end of treatment responders, two had a sustained response. Antiviral response to PEG-IFN-alpha-2a is different to that on standard IFN. In spite of a lower initial response PEG-IFN-alpha-2a/ribavirin combination therapy may overcome predicted IFN unresponsiveness.

Combination of interferon induction therapy and ribavirin in chronic hepatitis C.

The initial clearance of hepatitis C virus (HCV) during interferon-alfa therapy is dose-dependent. Therefore, higher initial interferon doses (induction therapy) may improve treatment results. This concept was tested in a prospective, randomized controlled trial. Previously untreated patients with chronic hepatitis C were randomized to receive 3 different interferon doses during the first 14 weeks of therapy (Group A, n = 130: 10 MU IntronA [AESCA-Schering Plough, Traiskirchen, Austria]/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; Group B, n = 124: 5 MU/day for 14 weeks; Group C, n = 119; 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. Throughout the whole study all patients received 1 to 1.2 g ribavirin/day. On treatment, no differences in viral clearance rates were observed. Sustained response rates were also not different among the groups (A: 48.5%, B and C: 41.3%, intent to treat). When data were analyzed according to genotypes, sustained response was almost twice as high in patients with genotype 1 receiving high-dose interferon induction therapy (A: 44.2%, B: 28.6%, C: 27%, P <.05). In contrast, results were not different in genotype 3a patients (A: 61.3%, B: 75.9%, C: 56.3%; P >.1). These data indicate that high-dose interferon induction therapy may improve the outcome of interferon/ribavirin combination therapy in genotype 1 patients.

Treatment of patients with chronic hepatitis C not responding to interferon with high-dose interferon alpha with or without ribavirin: final results of a prospective randomized trial. Austrian Hepatitis Study Group.

OBJECTIVE: To investigate the efficacy of high-dose interferon alpha (IFN-alpha) with or without ribavirin in interferon (IFN) non-responders. STUDY DESIGN: 304 chronic hepatitis C patients received 5 MU IFN-alpha2b (IntronA, Schering-Plough, Kenilworth, NJ, USA) three times a week for 3 months. Non-responders were randomized either to continue with IFN (IFN 5 MU/TIW followed by 10 MU/TIW, each for 3 months) alone (group A: n = 76, m: f = 54: 22, age 45.7 +/- 12 years, 16% cirrhosis, alanine aminotransferase [ALT] 66 +/- 35 U/l) or in combination with ribavirin (approximately 14 mg/kg/day) (group B: n = 81, m: f = 57: 24, age 48.2 +/- 12 years, 17% cirrhosis, ALT 71 +/- 40 U/l). At the end of treatment, patients were followed for 6 months. MAIN OUTCOME MEASURES: Virological response at end of treatment and 6 months thereafter. SETTING: University hospitals and tertiary referral centres. RESULTS: At the end of treatment, eight (10.8%) and 25 (31.3%, P= 0.0066) patients were HCV-RNA negative, and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in each group. Six months after treatment, only one patient in group A (1.3%) and seven patients (8.6%, P= 0.06) in group B had normal ALT and undetectable serum HCV-RNA. CONCLUSIONS: A combination of high-dose IFN with ribavirin induces a short-lasting complete response in about one-third of IFN-non-responders.

Dedicated extremity MR imaging of the foot and ankle.

The purpose of this review is to provide illustrative examples of diseases of the foot and ankle when imaged with a low-field MR imaging system. A retrospective review of 268 foot and ankle examinations, performed in our institution within the past 3 years with a 0.2-T (Artoscan Esaote, Genoa, Italy) dedicated extremity MR system was done. Additionally, illustrative comparison with conventional radiography and high-field MR imaging is presented in patients in whom these examinations were also performed. Although motion artifact limited the value of a few studies, in the majority of examinations low-field MR imaging provided diagnostic image quality for the full spectrum of disorders affecting the foot and ankle and seemed to be a feasible alternative to high-field MR imaging in establishing an accurate diagnosis.

The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C.

BACKGROUND & AIMS: Elevated hepatic iron concentration may affect the response to antiviral therapy in chronic hepatitis C. This study explored the contribution of genetic hemochromatosis to iron accumulation in chronic hepatitis C. METHODS: HFE mutations (C282Y and H63D) were assessed in 184 patients with chronic hepatitis C virus and 487 controls. Liver biopsy specimens were available in 149 patients. Hepatic iron content was measured in 114 patients by atom-absorption spectrophotometry. RESULTS: The C282Y and H63D allele frequencies were 7.06 and 11.6 in patients and 4.83 and 11.09 in controls, respectively. Eight patients were homozygotes (5 C282Y [2.7%] and 3 H63D [1.6%]), 2 compound heterozygotes (1%), and 49 heterozygotes (14 C282Y [7.6%] and 35 H63D [19%]). Biochemical evidence of iron overload was more common in patients with HFE mutations (28 of 47) than in those without (34 of 102; P = 0.0045). Histological iron grading and hepatic iron content overlapped among patients with or without mutations. A hepatic iron index of >1.9 was observed only in 1 of the 4 C282Y homozygotes and 1 of the 3 H63D homozygotes. CONCLUSIONS: HFE mutations contribute to but do not fully explain hepatic iron accumulation in chronic hepatitis C. Furthermore, C282Y or H63D homozygosity in chronic hepatitis C is not necessarily associated with a high hepatic iron content.

Interim analysis of a randomized controlled trial of combination of ribavirin and high dose interferon-alpha in interferon nonresponders with chronic hepatitis C.

UNLABELLED: This trial investigated the efficacy of a combination of high-dose interferon-alpha (IFN-alpha) with ribavirin in IFN nonresponders. STUDY PROTOCOL: 304 patients with chronic hepatitis C were treated with 5 MU IFN-alpha2b (IntronA(R), Schering-Plough) per TIW for 3 months. Nonresponders (defined by HCV-RNA positivity in serum after the 3 months of therapy) were randomized either to continue with IFN (5 MU IFN per TIW followed by 10 MU per TIW for each 3 months) alone (group A) or in combination with ribavirin (1-1.2 g per day) (group B). ALT was measured in monthly intervals, HCV-RNA in 3 monthly intervals. Pretreatment characteristics of the randomized patients were as follows: group A, n = 76; m/f, 54/22; 16% cirrhosis, age, 45. 7 +/- 12 years; ALT (U per litre), 66 +/- 35; group B, n = 81; m/f, 57/24; 17% cirrhosis, age, 48.2 +/- 12; ALT, 71 +/- 40. After 9 months of treatment, nine (11.6%) and 27 (32.5%, P = 0.0066) patients were HCV-RNA negative and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in group A and 15 in group B. Six months after treatment only two patients in group A (2.5%) and five (6%, P = 0.06) in group B had normal ALT and no detectable HCV-RNA in serum. In addition to the well-known side-effects of IFN the mean haemoglobin concentration dropped by 2 g per litre in group B. These data indicate that a combination of high-dose IFN with ribavirin is effective in inducing a short-lasting complete response in one-third of IFN nonresponders. Prolonged treatment with IFN/ribavirin may be necessary to obtain a sustained response.

Predominance of the HLA-H Cys282Tyr mutation in Austrian patients with genetic haemochromatosis.

BACKGROUND/AIMS: Genetic haemochromatosis is the most common autosomal recessive disorder in Northern European populations. A major histocompatibility complex class I-like gene, HLA-H, has been proposed to be responsible for genetic haemochromatosis. The prevalence of HLA-H gene mutations 282(TGC; Cys/TAC; Tyr) and 63(CAT; His/GAT; Asp) was determined in patients of Austrian origin. METHODS: DNA extracted from the blood of 40 Austrian patients and 271 controls was used to amplify HLA-H gene fragments by the polymerase chain reaction method. The base changes responsible for mutations Cys282Tyr and His63Asp alter recognition sites for restriction enzymes SnaB I and Bcl I, respectively. Digestion products were separated by agarose gel electrophoresis and visualised by ethidium bromide staining. RESULTS: Thirty-one (77.5%) genetic haemochromatosis patients were homozygous for mutation Cys282Tyr and three compound heterozygous for mutations Cys282Tyr and His63Asp. One patient was homozygous for mutation His63Asp but normal for mutation Cys282Tyr. Four patients were normal at both genetic loci and one patient was heterozygous for mutation His63Asp. One control subject homozygous for mutation Cys282Tyr was found on investigation to fulfill diagnostic criteria for haemochromatosis. Eight control subjects homozygous for mutation His63Asp showed no biochemical or clinical evidence of haemochromatosis indicating that this variant is not directly responsible for haemochromatosis. Absence of the Cys282Tyr mutation in six genetic haemochromatosis patients with distinct haplotypes indicates mutations within the HLA-H gene or at alternative genetic loci are the cause of genetic haemochromatosis in these patients. CONCLUSIONS: The HLA-H Cys282Tyr defect is likely to play a key role in the pathogenesis of haemochromatosis in most patients. Predominance of a single HLA-H gene mutation in haemochromatosis allows presymptomatic screening by genotypic analysis.

High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a pilot study.

Acute hepatitis C takes a chronic course in 50-80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-alpha2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested using PCR prior to treatment, three times weekly during the first two weeks of treatment, and then once weekly until the end of therapy. During the 15-month follow-up, HCV-RNA tests were performed monthly up to month 6 and every two to three months thereafter. Twenty-four patients were enrolled at the time of writing; age ranged from 18 to 76 years (mean = 32), and nine patients were men. All patients presented with cholestatic hepatitis; 19 were actively abusing intravenous drugs, four had no known parenteral exposure, and one was a medical laboratory technician. All patients were anti-HCV positive, HCV-RNA positive, and HIV negative. Five patients were infected with genotype 3, five with genotype 1a, five with genotype 1b, three with genotypes 3 and 2, and one with genotypes 1 and 2. All patients exhibited normalized serum transaminase concentrations within 18-43 days; HCV-RNA became negative in all patients within 4-12 days. Toxicity did not exceed grade 1 and disappeared within three days of treatment. In the follow-up period, which ranged from six to 29 months (mean = 19.5 +/- 10.4), serum ALT concentrations remained normal and HCV-RNA remained negative in all patients except two dropouts and two patients who developed relapsing disease after having been HCV-RNA negative for three and eight months, respectively. In both patients, the same HCV genotype 3 reemerged. Serum ALT concentrations ranged from 531 to 1940 IU/liter (mean = 1055; normal < 22). Concentrations of HCV-RNA (Quantiplex; Chiron, Emeryville, California) were < 3.5 x 10(5) eq/ml in nine of 14 PCR-positive patients. In the other five patients, concentrations ranged from 10.4 x 10(5) eq/ml to 131.6 x 10(5) eq/ml (mean = 69.6 x 10(5)). No correlation was observed between HCV-RNA concentrations and serum ALT concentrations at presentation (r = 0.331; P = 0.67) and total dose of interferon-alpha2b administered until normalization of ALT (r = -0.088; P = 0.74). Twenty-two of 24 patients completed treatment (two were noncompliant). Of these, 20 achieved a complete response (HCV-RNA negative for at least six months). Two of these patients relapsed, and 18 (90%) remained HCV-RNA negative for 18.65 (+/-9.7) months. These findings suggest that high-dose interferon-alpha2b is well tolerated and effective in preventing a chronic course of hepatitis C infection.