Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

Pneumatosis intestinalis: a rare cause of lower gastrointestinal bleeding.

Pneumatosis intestinalis is an uncommon condition characterized by the presence of gas in the bowel wall. We present the case of a 49-year-old man admitted to our Clinic for his 4 day long haematochezia. Colonoscopy revealed pneumatosis coli as a cause of the lower gastrointestinal bleeding. A wide range of diagnostic methods didn't show any underlying disease related to the bleeding, other than the presence of gas. Patient is reported in order to draw attention to the primary pneumatosis coli presented as a rare cause of haematochezia.

Intrahepatic type II gall bladder perforation by a gall stone in a CAPD patient.

INTRODUCTION: Perforation of the gall bladder represents a rare, but life-threatening complication of cholecystitis. Clinical presentation may vary between severe peritonism in acute perforation and absence of symptoms in subacute or chronic progression of perforation. Abdominal imaging like ultrasound or CT-scan are important tools for immediate diagnose of gall bladder perforation. CASE PRESENTATION: We report a case of a 30-year old female patient with end-stage kidney disease treated by continuous ambulatory peritoneal dialysis (CAPD) who was admitted to the emergency room with fever and mild abdominal pain. A type II gall bladder perforation by a solitary gall stone with development of a liver abscess was detected by abdominal ultrasound. CONCLUSION: Gall bladder perforations are rare but have to be considered in patients with abdominal pain and fever. Abdominal ultrasound is a reliable tool to establish diagnosis.

[The clinical spectrum of urea cycle defects in adult patients]. / Das klinische Spektrum von Harnstoffzyklusdefekten im Erwachsenenalter.

Urea cycle defects belong to the most common metabolic disorders with a cumulative incidence of 1:8000. A common trait of urea cycle defects is a disturbed detoxification of ammonia leading to hyperammonemia in the event of a high nitrogen load. Most patients develop symptoms in the neonatal period or in infancy, e. g. vomiting, seizures and disturbed consciousness. Depending on the affected enzyme and its residual activity, patients differ in the age at first presentation, the character and severity of symptoms and in the susceptibility to metabolic derangement. The presence of hyperammonemia and an altered plasma amino acid profile give the essential diagnostic clues. Since modern therapeutic measures have prolonged the life expectancy of these patients and provided the possibility of a first presentation in adulthood, patients with urea cycle defects have become an increasing challenge in internal medicine. The reported case series illustrates the heterogeneous clinical course of these disorders from childhood to adulthood.

Retrospective analysis of chronic hepatitis D in a West German University Clinic over two decades: migratory pattern, prevalence and clinical outcome.

BACKGROUND/AIMS: Epidemiology, clinical features and long term-course of chronic hepatitis D were addressed in a non-endemic Central European area. METHODS: Sixty-seven patients with chronic hepatitis D were identified among 1307 HBsAg carriers at the university hospital Düsseldorf during two decades (1989 - 2008) and followed for a mean of 7 +/- 6 years. Forty-one of these were treated with IFN-alfa for at least six months. RESULTS: Hepatitis D prevalence increased from 4.1 to 6.2 % among HBsAg carriers during the two decades (p < 0.06). Patients originating from the former Soviet Union (32.1 vs. 46.2 %) and Africa (0 vs. 17.9 %) became more frequent whereas the prevalence of patients from Southern Europe declined (46.5 vs.17.9 % p < 0.03). The time span between the diagnosis of hepatitis B and D was 4.8 +/- 7 years (p < 0.0001). A sustained virological response to interferon-alfa was achieved in 19.5 % of the patients. The yearly incidence rates for death, HCC and complications were 3.2 %, 2.7 % and 8 % among patients with liver cirrhosis. Estimated survival and complication-free survival during 12 years were 72 % and 45 % in cirrhotic compared to 100 % in non-cirrhotic patients (p < 0.008 and p < 0.0001, respectively). CONCLUSION: Hepatitis D in western Germany appears to be on the increase and has a migration background that should be considered in clinical practice. Clinical outcome and response to IFN are as poor as in endemic regions, indicating the need to improve early diagnosis.

Chicken thrombocytes express the CD51/CD61 integrin.

A panel of commercially available anti-human mab was screened for cross-reactivity on chicken cells. All mab were screened at least twice on PBL collected from two different chicken lines. Out of the 377 mab tested, only two consistently reacted with subpopulations of PBL. The mab HUH73A reactive with CD11a was detected on all lymphocytes. In contrast, the mab 23C6 obtained from Serotec and reactive with an epitope formed by humanVbeta3 integrin chains (CD51/CD61) reacted with all thrombocytes, but not with other cells. In double immunofluorescence analyses, the 23C6+ cells were found to coexpress the CD45 antigen and the chicken thrombocyte marker K1. The chicken genes encoding CD51 and CD61 were analyzed by database mining. The CD51 gene is encoded by a 43 kb region containing 30 exons on chicken chromosome 7, whereas the 16 kb CD61 gene consisted of 15 exons and was localized to chromosome 27. In conclusion, the mab 23C6 is a useful reagent to identify chicken thrombocytes.

Effect of feeding soybean meal and differently processed peas on the gut mucosal immune system of broilers.

Peas are traditionally used as a protein source for poultry. However, peas contain antinutritional factors (ANF), which are associated with the initiation of local and systemic immune reactions. The current study examined the effect of feeding raw or differently processed peas in comparison with feeding a soybean meal (SBM) based control diet (C) on the gut mucosal immune system of broilers in a 35 day feeding trial. In six replicates, a total of 360 one-day-old male broilers were randomly allocated to four different groups receiving C, or three treatment diets containing raw, fermented, and enzymatically pre-digested peas, each supplying 30% of required crude protein. After slaughtering, jejunal samples were taken for immunohistochemical, flow cytometric, and gene expression analyses. Investigations were focused on the topological distribution of intraepithelial leukocytes (villus tip, villus mid, and crypt region) as well as on the further characterization of the different intraepithelial lymphocytes (IEL) and concomitant pro- and anti-inflammatory cytokines. Broilers receiving the raw or processed pea diets had higher numbers of intraepithelial CD45+ leukocytes in the tip (P = 0.004) and mid region (P < 0.001) of villi than birds fed C. Higher numbers of intraepithelial CD3+ lymphocytes were found in the villus tip (P = 0.002) and mid region (P = 0.003) of birds fed raw or processed pea containing diets in comparison with those fed C. The flow cytometric phenotyping showed a similar relative distribution of IEL among the feeding groups. The expression of intestinal pro- and anti-inflammatory cytokines was affected by feeding the different diets only to a minor extent. To conclude, feeding of diets formulated with raw and processed peas in comparison with feeding a SBM control diet initiated mucosal immune responses in the jejunum of broilers indicated by a quantitative increase of intraepithelial T cells. Further research is needed in order to ascertain the specific factors which are responsible for observed local immune reactions and how these local reactions might affect the immune status and health of broilers.

Cytokines of birds: conserved functions--a largely different look.

Targeted disruptions of the mouse genes for cytokines, cytokine receptors, or components of cytokine signaling cascades convincingly revealed the important roles of these molecules in immunologic processes. Cytokines are used at present as drugs to fight chronic microbial infections and cancer in humans, and they are being evaluated as immune response modifiers to improve vaccines. Until recently, only a few avian cytokines have been characterized, and potential applications thus have remained limited to mammals. Classic approaches to identify cytokine genes in birds proved difficult because sequence conservation is generally low. As new technology and high throughput sequencing became available, this situation changed quickly. We review here recent work that led to the identification of genes for the avian homologs of interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma, various interleukins (IL), and several chemokines. From the initial data on the biochemical properties of these molecules, a picture is emerging that shows that avian and mammalian cytokines may perform similar tasks, although their primary structures in most cases are remarkably different.

T cell development in the chicken.

This review summarizes our current view of gamma delta and alpha beta T cell development in the chicken. In it we emphasize the functional interplay between the gamma delta and alpha beta T cell subpopulations.

Use of endoscopy and renal biopsy for the diagnosis of kidney disease in free-living birds of prey and owls.

Eighty-nine free-living birds of prey and owls were examined and blood samples and radiographs were taken. In addition, 126 specimens of renal tissue were obtained without complications, with a mean postbiopsy haemorrhage time of 67 seconds. On average, the samples were 2.2 mm long, 1.3 mm wide and 1.0 mm deep and they all contained proximal and distal tubuli and from one to 89 glomeruli; 49 of them contained from one to four intralobular veins, and on average each sample contained 10.7 per cent air sac tissue; 113 of the 126 samples could be evaluated histologically.

[Therapy trials with enrofloxacin (Baytril) in a laying hen flock with Salmonella pullorum infections]. / Therapieversuch mit Enrofloxacin (Baytril) in einer Legehennenherde mit Pullorum-Salmonellose.

The course of a disease due to Salmonella pullorum in laying chickens is described. The experimental application of enrofloxacin (Baytril) at a dosage of 100 mg/l drinking water for 10 days resulted in a stop of the mortality rate, increment of egg production and reduction of Salmonella excretion. A recurrence of the disease was observed in the fifth week following the end of treatment with high mortality and decreasing egg laying. The treatment lead to a short-dated success but a permanent elimination of the germ from the flock was not achieved.

[Current therapy of hepatocellular carcinoma with special consideration of new and multimodal treatment concepts]. / Aktuelle Therapie des hepatozellulären Karzinoms unter besonderer Berücksichtigung neuer und multimodaler Therapiekonzepte.

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide due to the growing number of hepatitis C related HCCs. In more than 80% of the patients, HCC arises in a cirrhotic liver. Furthermore, more than half of the patients have an advanced Child-Pugh score or an inoperable tumor stage at the initial diagnosis. Recommendations for the treatment of HCC by national and international guidelines rely on the BCLC ("Barcelona Clinic for Liver Cancer") algorithm. Depending on the stage of liver function and tumor disease it recommends resection, liver transplantation, radiofrequency thermal ablation (RFA), transarterial chemoembolisation (TACE), systemic therapy with sorafenib or best supportive care, but does neither take into consideration combination of therapies nor new therapy modalities. However, there is increasing evidence that combinations i. e. sorafenib with TACE or combination of locoregional techniques enhance effectivity and tumor control compared to monotherapies. TACE with drug-eluting beads, selective internal radiotherapy (SIRT) and new locoregional therapy procedures like microwave ablation (MWA) are further promising therapeutic approaches. Patients with HCC should be discussed in a local tumor board in order to provide the optimal and most individual way of treatment.

[Blood collection techniques and normal serum values of important parameters of the Greek land tortoise (Testudo hermanni hermanni)]. / Blutentnahmetechnik und Serumnormalwerte wichtiger Parameter bei der griechischen Landschildkröte (Testudo hermanni hermanni).

The technique and sites of blood sampling in the Herman's tortoise (Testudo hermanni hermanni) are explained. Advantages and disadvantages of each site (Vena coccygealis dorsali, Vena ulnaris) are discussed in comparison to cardiac puncture and clipping a nail. The diagnostic importance of blood examination is shown. Normal values of important blood parameters in clinically healthy animals (n = 17) are given, determined by a dry chemistry system (Kodak Ektachem).

[Blood chemical parameters for wild raptor patients and their changes after liver biopsy]. / Blutchemische Parameter bei Wildgreifvogelpatienten und deren Veränderung nach Leberbiopsieentnahme.

The present paper tried to find relations between specific anamnesis of wild raptors and blood chemistry values at their day of presentation. 60 (88%) of 68 presented birds of prey showed changes in their blood values. In most birds an increase of GOT, GPT and AP was seen. Some birds showed increases of uric acid, urea and changes in the relation of Ca and P as well. A comparison between Eurasian buzzards with fractures and some without clinical signs showed a significant increase of uric acid, urea, potassium and inorganic phosphorus in the group of fractured birds. Changes of blood chemistry values after liver biopsy are investigated in the second part of the present study. Liver- and kidney values showed an increase after the biopsy. Kestrels (Falco tinnunculus) showed the maximum of the increase at the first day after biopsy while Eurasian buzzards (Buteo buteo) had the maximum at the third and Black kites (Milvus migrans) at the fifth day after biopsy.

[Occurrence of parasites in indigenous birds of prey and owls]. / Untersuchungen zum Vorkommen von Parasiten bei einheimischen Greifvögeln und Eulen.

In the present paper a general overview on parasites in birds of prey and owls is given. This part is followed by a study investigating the prevalences and species of parasites in free-ranging birds of prey and owls in Berlin and Brandenburg State, Germany. Over a one year period, 84 birds of prey and owls of the following species were examined for the presence of endo- and ectoparasites: Common Buzzard (Buteo buteo) (n = 32), Kestrel (Falco tinnunculus) (n = 20), Sparrowhawk (Accipiter nisus) (n = 9), Goshawk (Accipiter gentilis) (n = 8), Black Kite (Milvus migrans) (n = 4), Peregrine Falcon (Falco peregrinus) (n = 3), Marsh Harrier (Circus aeruginosus) (n = 1), White-tailed-Sea Eagle (Haliaeetus albicilla) (n = 1), Tawny Owl (Strix aluco) (n = 4), Long-eared Owl (Asio otus) (n = 1) and Barn Owl (Tyto alba) (n = 1). In 97.6% of the cases, ectoparasites (feather mites and hippoboscid flies) were found. Especially eyasses (93.3%) were positive for hippoboscid flies. Trichomonas was detected in 28.6% of all birds of prey and owls examined. A prevalence of 100% was established in the Sparrow Hawks as well as Peregrine Falcons. Leucozytozoon sp. and Hemoproteus sp. as blood parasites were found in 26.9% of the birds in total. Common Buzzards showed the highest prevalence (44.8%). 58.3% of birds examined were positive for endoparasites. Flukes were found in 16.7%, tapeworms in 14.3%, round-worms in 48.8% and acanthocephales in 2.4% of the cases. Interestingly, Tylodelphis clavata (in a Common Buzzard) and Hovorkonema variegatum (in a Goshawk) were found for the first time in raptors. The results of this study underline the importance of a parasitological examination in the process of raptor rehabilitation.

The chicken TCR zeta-chain restores the function of a mouse T cell hybridoma.

The TCR/CD3 complex has been intensively studied in mammals, but it has been difficult to isolate homologues in other vertebrates. Here, we characterize the chicken zeta-chain, the first nonmammalian homologue identified. The comparison of mammalian and chicken zeta proteins revealed high identity of the transmembrane and the C-terminal cytoplasmic domains. Transfection of a mouse zeta-deficient cell line, with the chicken zeta gene, restored surface expression of the murine TCR/CD3 complex. The chicken zeta-chain was stably associated with the mouse TCR/CD3 components and fully restored its signaling capacity upon stimulation with Ab, superantigen, and peptide Ag. This is the first report of a nonmammalian TCR component that is capable of fully restoring a mammalian TCR in every aspect analyzed, thus demonstrating the enormous selective pressure to maintain the zeta-chain as a structural and signaling component over a period of 300 million years.