25 research outputs found
Natural course and treatment outcome in hepatitis C recurrence after liver transplantation
No full textHepatitis C virus (HCV) infection post-liver transplantation (post-LT) is associated with an increased rate of fibrosis progression compared to non-transplanted patients. Thus, 25% of the recipients will progress to cirrhosis within 5 years after LT. Antiviral treatment after LT with peg-INF and ribavirin (RBV) yields lower sustained viral response (SVR) than in nontransplanted patients. In many LT-recipients non-response to treatment will eventually lead to progression to cirrhosis.The aim of this thesis was to study the natural course and treatment outcome in liver transplant patients with hepatitis C recurrence, and the influence of baseline factors on the course of the HCV recurrence and antiviral treatment, with particular emphasis on HCV genotype and IL28B gene polymorphism.In paper I we conducted a pilot-study on 21 hepatitis C LT recipients with the aim to increase adherence and tolerance to antiviral treatment. All recipients were pre-treated with Darbepoetin (EPO) starting 2 weeks before the initiation of Peg-IFN and RBV. RBV was dosed taking weight and kidney function into account, with a target serum concentration set to10 μM/L by using a formula to calculate the dose. A majority of patients achieved the target concentration, and 90% could stay adherent to a full treatment course. SVR was reached in 18% recipients with genotype 1 and 60% with genotype non-1. Recipients with mild fibrosis achieved SVR in 67%.In paper II we studied the influence of IL28B gene polymorphism on fibrosis progression and treatment outcome in 54 LT recipients, who had received antiviral treatment, and in 45 of their donors. The most favorable IL28B genotype CC was associated with slower fibrosis progression and better treatment outcome. Patients with HCV genotype non-1 and the IL28B CC gene achieved SVR in 71%, whereas patients with genotype 1 and IL28B non-CC did so in only 23%, p In paper III we treated 46 Swedish and 8 Norwegian patients with the treatment regimen evaluated in paper I. 94% stayed adherent to the treatment course. SVR was achieved in 82% of recipients with HCV genotype 2/3 versus in only 22% with genotype 1, p In paper IV we evaluated the utility of an early liver biopsy post-LT to detect and predict fibrosis progression of recurrent HCV infection post-LT. 35 HCV RNA positive, and 11 HCV RNA negative LT recipients, who underwent protocolled liver biopsies 6 and 12 months post-LT, were studied. Histological recurrence with fibrosis stage ≥ F1was noted in 56% of the HCV positive LT recipients at 6 months, and in 82% 12 months post-LT. Acute cellular rejection (ACR) and IL28B genotype CC were associated with a more pronounced fibrosis progression 12 months post-LT. Fibrosis was absent in all eleven recipients who were HCV RNA negative directly after LT. Thus, a 6 months biopsy post-LT is a valuable tool for detection of an early HCV recurrence, which makes an early treatment intervention for HCV possible.List of scientific papersI. Ackefors M, Gjertsen H, Wernerson A, Weiland O. Concentration-guided ribavirin dosing with darbepoetin support and peg-IFN alfa-2a for treatment of hepatitis C recurrence after liver transplantation. J Viral Hepat. 2012 Sep;19(9):635-9. https://doi.org/10.1111/j.1365-2893.2012.01587.x. II. Ackefors M, Nystrom J, Wernerson A, Gjertsen H, Sonnerborg A, Weiland O. Evolution of fibrosis during HCV recurrence after liver transplantation - influence of IL-28B SNP and response to peg-IFN and ribavirin treatment. J Viral Hepat. 2013 Nov;20(11):770-8 https://doi.org/10.1111/jvh.12099. III. Ackefors M, Castedal M, Dahlgard O, Verbaan H, Gjertsen H, Wernerson A, Weiland O. Cost-effective treatment for genotype 2 and 3 Hepatitis C Recurrence after Liver Transplantation. [Submitted]IV. Ackefors M, Wernerson A, Gjertsen H, Weiland O. The utility of an early liver biopsy to predict fibrosis progression of recurrent hepatitis C after liver transplantation. [Submitted]</p
Natural course and treatment outcome in hepatitis C recurrence after liver transplantation [Elektronisk resurs]
No full textHepatitis C virus (HCV) infection post-liver transplantation (post-LT) is associated with an increased rate of fibrosis progression compared to non-transplanted patients. Thus, 25% of the recipients will progress to cirrhosis within 5 years after LT. Antiviral treatment after LT with peg-INF and ribavirin (RBV) yields lower sustained viral response (SVR) than in nontransplanted patients. In many LT-recipients non-response to treatment will eventually lead to progression to cirrhosis. The aim of this thesis was to study the natural course and treatment outcome in liver transplant patients with hepatitis C recurrence, and the influence of baseline factors on the course of the HCV recurrence and antiviral treatment, with particular emphasis on HCV genotype and IL28B gene polymorphism. In paper I we conducted a pilot-study on 21 hepatitis C LT recipients with the aim to increase adherence and tolerance to antiviral treatment. All recipients were pre-treated with Darbepoetin (EPO) starting 2 weeks before the initiation of Peg-IFN and RBV. RBV was dosed taking weight and kidney function into account, with a target serum concentration set to10 μM/L by using a formula to calculate the dose. A majority of patients achieved the target concentration, and 90% could stay adherent to a full treatment course. SVR was reached in 18% recipients with genotype 1 and 60% with genotype non-1. Recipients with mild fibrosis achieved SVR in 67%. In paper II we studied the influence of IL28B gene polymorphism on fibrosis progression and treatment outcome in 54 LT recipients, who had received antiviral treatment, and in 45 of their donors. The most favorable IL28B genotype CC was associated with slower fibrosis progression and better treatment outcome. Patients with HCV genotype non-1 and the IL28B CC gene achieved SVR in 71%, whereas patients with genotype 1 and IL28B non-CC did so in only 23%, p < 0,016. Patients with mild fibrosis (F1-2) had better treatment outcome than patients with advanced fibrosis. In paper III we treated 46 Swedish and 8 Norwegian patients with the treatment regimen evaluated in paper I. 94% stayed adherent to the treatment course. SVR was achieved in 82% of recipients with HCV genotype 2/3 versus in only 22% with genotype 1, p < 0.002. Patients with IL28B CC achieved SVR in 73% and patients with non-CC in 33%, p < 0.001. Patients with mild fibrosis achieved SVR in 56% and patients with advanced fibrosis in 26% p < 0.01. Thus, with favorable HCV genotype and IL28B genotype, LT recipients have a good chance to achieve SVR, when treated before advanced fibrosis has developed. In paper IV we evaluated the utility of an early liver biopsy post-LT to detect and predict fibrosis progression of recurrent HCV infection post-LT. 35 HCV RNA positive, and 11 HCV RNA negative LT recipients, who underwent protocolled liver biopsies 6 and 12 months post-LT, were studied. Histological recurrence with fibrosis stage ≥ F1was noted in 56% of the HCV positive LT recipients at 6 months, and in 82% 12 months post-LT. Acute cellular rejection (ACR) and IL28B genotype CC were associated with a more pronounced fibrosis progression 12 months post-LT. Fibrosis was absent in all eleven recipients who were HCV RNA negative directly after LT. Thus, a 6 months biopsy post-LT is a valuable tool for detection of an early HCV recurrence, which makes an early treatment intervention for HCV possible
Growth, molting, food ingestion, and absorption in juvenile Macrobrachium rosebergii in relation to dissolved oxygen
No full textGrowth, molting, food ingestion, and absorption in juvenile Macrobrachium rosenbergii were evaluated at 2.5, 3.5, 5.0, and 7.7ppm dissolved oxygen (DO), 29°C, and 0.5°/oo salinity. DO levels were maintained by bubbling nitrogen gas against water flowing down through PVC gas-exchange columns. Prawns (0.58 to 0.60g dry weight) were grown individually in 4 l glass chambers for 40 days and fed in excess twice daily. In a separate experiment, food ingestion and absorption in prawns (0.66 to 1.36g dry weight acclimated to the tour DO levels were determined gravimetrically. Growth rate was significantly reduced only at 2.5ppm DO. The mean growth rates, as percentage dry weight increase per day, were 0.76, 1.56, 1.81, and 1.76% at 2.5, 3.5, 5.0, and 7.7ppm DO, respectively. Molting was not inhibited at the tour DO levels tested. Intermolt periods of all prawns ranged trom 8 to 18 days with a mean of 13.6 days. Food ingestion was reduced at 2.5ppm DO, but apparent absorption of dry matter was independent of oxygen at the tour levels tested. Mean ingestion rates, as percentage of dry body weight were 5.51, 8.85, 8.05, and 10.35%. The mean apparent absorption efficiency of all prawns was 87.95%. This study showed that juvenile M. rosenbergii requires about 3.5ppm DO to grow optimally in the laboratory. Reduction in growth of M. rosenbergii at DO levels below 3.5ppm is due in part to a reduction in food intake and not to changes in absorption efficiency and molting frequency
Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM
No full textThe prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. Radioligand binding assays for IgG Ab used immunoprecipitation of in vitro translated 35S-GAD. We found autoantibodies to GAD65 in 116 of 155 (75 %), to GAD67 in 19 of 155 (12 %) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16 %) (p < 0.0001) IDDM sera. GAD67Ab were found almost exclusively (17 of 19, 89 %) in GAD65Ab-positive sera and the levels of GAD67Ab correlated with those of GAD65Ab (r 2=0.5913; p=0.009). GAD65Ab directed to GAD65-M were found in 104 of 155 (67 %), to GAD65-C in 104 of 155 (67 %) and to GAD65-M + C in 116 of 155 (75 %) of IDDM sera. and indicated reactivity to at least two distinct epitopes. Among the nine GAD65Ab-positive healthy children, two (22 %) were also positive with GAD67, nine (100 %) with GAD65-M + C, seven (78 %) with GAD65-M, eight (89 %) with GAD65-C and two (22 %) with GAD65-N-67. Titres of GAD65Ab (p = 0.007), GAD65-C-Ab (p = 0.002) and GAD65C+M-Ab (p=0.101), but not of GAD65-M-Ab (p = 0.101) were significantly higher in IDDM than in healthy children. We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children
The Zooplankton Of The Baltic Proper : A long-term investigation of the fauna, its biology and ecology
No full textThis paper is based on the results from a long-term zooplankton investigation in the Baltic proper in the years 1968—1972. Additional results, obtained by the authors in more recent investigations, have also been used in order to enrich the material with information not obtained in the principal investigation. Seven standard plankton stations, covering seven sub-areas of the Baltic proper have been visited on average four to five times per year. All cruises have been made in connection with ordinary hydrographical expeditions which means that all zooplankton samples are accompanied by a complete list of hydrographical data. The paper describes the zooplankton fauna of the Baltic proper which comprises about 40 regularly appearing species excluding the micro zooplankton. The main part of the fauna in respect of biomass and production consists, however, of only 10—12 species. The most important were the cnidarian Aurelia aurita. the rotifers Synchaeta spp., the cladocerans Bosmina coregoni maritima and Evadne nordmanni, the copepods Pseudocalanus minutas elongatus, Temora longicornis, Acartia bifilosa, A. longiremis and Centropages hamatus and the larvacean Fritillariaborealis. Species of less importance were the larvae of Pleurobrachia pileus, the cladocerans Podon intermedius, P. leuckarti and Pleopsis polyphemodides (the latter is abundant in coastal areas), the copepods Eurytemora sp. and Oithona similis, the larvae of gastropod species, Mytilus edulis, Macoma baltica, Cardium glaucum. C.hauniense and My a arenaria, the chaetognath Sagitta elegans baltica and the larvacean Oikopleura dioica. Occaisonal species were the cnidarians Sarsia tubulosa and Cyanea capillata, the rotifers Keratella quadrata quadrata, K. qu. platei, K. cruciformis eichwaldi and K.cochlearis recurvispina, the larvae of Pygospio elegans and Balanus improvisus, the copepods Calanus finmarchicus, Limnocalanus macrurus and Cyclops sp., the mysidaceans Mysis relicta and M. mixta, the amphipod Hyperia galba and the chaetognath Sagitta setosa. All samples have been collected by vertical, fractionated hauls with a Nansennet. The mesh size was 0.160 mm in the years 1968—1971 and 0.090 mm in 1972. A correction of all results due to the poor filtering capacity of the Nansen net has been made. The additional results are mainly based on samples from the UNESCOWP 2 net. All specimens have been analysed to species and the copepods also to developmental stages. The biomass has been calculated as the sum of all individual volumes. The paper also describes the hydrography of the Baltic proper in general and presents the data for temperature, salinity and oxygen in the years 1968—1972.The relationship between the unique hydrography of the Baltic with its stable, brackish water contidions and the planktonfauna is discussed. The regulating factors for the vertical and horizontal distribution of the fauna were found to be either temperature or salinity or a combination of these factors. The seasonal variation in biomass values showed a rather good correlation with the temperature of the surface layer viz. the lowest biomass values (< 10 g m-2) were usually found in March—April, an increase started in May—June and a maximum (30—60 g m-2) was most often reached in August—September. There were great variations in biomass between the seven stations. The highest mean values (20—25 gm"2) were found in the southern and south-eastern parts of the Baltic proper and the lowest (12—13 gm-2) in the northern and south-western parts. Looking at the biomass values over the whole period of investigation, a remarkable stability has been found. There is no evidence of either increasing or decreasing trend. The production of zooplankton has also been estimated. According to our calculations the production amounts to about 20 gC m-2 year-1 (380 g wwt) in the southern Baltic proper and 10 gC m-2 year-1 (190 g wwt) in the northern part. The last part of the paper discusses the role of zooplankton in the energy flow of the whole pelagic ecosystem, i.e. from primary phytoplankton production to reproduction and recruitment of pelagic fishes
Oceanography and global fish production
No full textShelf seas and large upwelling areas along the eastern side of the Atlantic and Pacific Oceans occupy 10 percent of the global ocean, but stands for some 80 percent of all marine fisheries. The deep ocean on the other hand, covering some 80 percent of the area, stands for a maximum of 15 percent of the fisheries. Here, the physical reasons (ocean circulation, including upwelling and mixing) behind these large differences in yield are discussed. Nutrient supply from land, and efficient nutrient recirculation due to mixing by tides and winds, enhance primary phytoplankton productivity and fish yields in the shelf seas. A strong upward flux of water and nutrients from intermediate depths boosts productivity and fish yields in upwelling areas
Concentration-guided ribavirin dosing with darbepoetin support and peg-IFN alfa-2a for treatment of hepatitis C recurrence after liver transplantation
No full textComparing feed intake, utilization of protein and energy for growth and body composition in S. solea fed natural and commercial diets
No full textThe present work was carried out to study the effect of polychaete Nereis virens on feed intake, utilization of protein and energy for growth and body composition in sole (S. solea). It is hypothesized that intake, efficiencies of protein utilization and growth rates obtained for sole fed ragworm are comparable to those previously reported for S. solea. The mussel M. edulis was used as a reference diet to allow comparisons of present results with those obtained previously, which until today serve as reference for optimum growth in sole. Intake, efficiencies of utilization for protein and energy for growth and growth rates obtained for sole fed ragworm are expected to be higher compared to commercial feed. A commercial feed, commonly used for turbot but also in sole culture served as a second reference diet to discuss differences between natural and commercial feeds
PCR with electrospray ionization-mass spectrometry on bronchoalveolar lavage for detection of invasive mold infections in hematological patients
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