The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C.

The outcome of hepatitis C virus (HCV) infection and the likelihood of a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. In vitro studies demonstrated that bile acids (BA) interfere with antiviral interferon effects. We investigate the influence of plasma BA concentrations and an ABCB11 polymorphism associated with lower transporter expression on viral load and SVR. Four hundred and fifty-one Caucasian HCV-patients treated with PEG-interferon and ribavirin were included in the study. ABCB11 1331T>C was genotyped, and plasma BA levels were determined. The 1331C allele was slightly overrepresented in HCV-patients compared to controls. In HCV-patients, a significant difference between patients achieving SVR vs non-SVR was observed for HCV-2/3 (5 vs 9 µm; P=0.0001), while median BA levels in HCV-1 were marginally elevated. Normal BA levels <8 µm were significantly associated with SVR (58.3%vs 36.3%; OR 2.48; P=0.0001). This difference was significant for HCV-2/3 (90.7%vs 67.6%; P=0.002) but marginal in HCV-1 (38.7%vs 27.8%; P=0.058). SVR rates were equivalent between ABCB11 genotypes for HCV-1, but increased for HCV-2/3 (TT 100%vs CC 78%; OR 2.01; P=0.043). IL28B genotype had no influence on these associations. No correlation between BA levels and HCV RNA was detected for any HCV genotype. The higher allelic frequency of ABCB11 1331C in HCV-patients compared to controls may indirectly link increased BA to HCV chronicity. Our data support a role for BA as host factor affecting therapy response in HCV-2/3 patients, whereas a weaker association was found for HCV-1.

Lessons from a transplant patient with diarrhea, cryptosporidial infection, and possible mycophenolate mofetil-associated colitis.

Diarrhea in a transplant recipient may be caused by infection, metabolic problems, or adverse drug effects. The immunosuppressive drug most frequently associated with diarrhea in transplant recipients is mycophenolate mofetil (MMF). We present the case of a patient with 2 potential explanations for diarrhea lasting several weeks, which occurred years after liver transplantation. Whereas stool samples were positive for cryptosporidia, the histopathological findings were compatible with MMF colitis. However, diarrhea resolved after treatment of cryptosporidial infection, despite continued MMF medication. This case shows that histopathological findings of MMF colitis may be misleading and do not prove that diarrhea is drug induced.

Sensitisation to Ambrosia in Switzerland: a public health threat on the wait.

BACKGROUND: Ambrosia artemisiifolia (short name = Ambrosia common ragweed) pollen is a potent allergen and has recently been found in Switzerland, spreading from the southwest of the country. The aim of this study is to describe Ambrosia sensitisation rates in the population-based SAPALDIA cohort (Swiss Study on Air Pollution And Lung Diseases In Adults) and to test whether an increase in these rates could be observed. METHODS: Among the 6345 participants from 8 areas who provided blood samples in 1991 and 2002, 5823 had valid results for specific IgE against common inhalant allergens tested with Phadiatop. In 2002 Ambrosia sensitisation was measured and positive tests were analysed for Artemisia vulgaris (mugwort). Blood samples taken in 1991 in Ticino and Geneva were also tested for Ambrosia. RESULTS: Sensitisation rate (Phadiatop) did not increase significantly between the two surveys and sensitisation was found in 30% of the participants. A proportion of 7.9% showed specific IgE to Ambrosia pollen. The sensitisation rate in Lugano and Geneva had not changed substantially since 1991. Among those sensitised to Ambrosia 82% also showed specific IgE against Artemisia, suggesting a high rate of cross-reactivity. Only 1.3% were sensitized to Ambrosia alone. The incidence of asthma or hay fever in participants with specific IgE to Ambrosia pollen was not higher than in the general study population. CONCLUSION: Currently Ambrosia pollen does not appear to be an important cause of inhalant allergies in Switzerland. Sensitisation rates are low and have not increased since 1991. Due to cross-reactivity Ambrosia sensitisation may be a consequence of primary sensitisation to Artemisia. Elimination of Ambrosia plants is nevertheless mandatory to avoid a future increase.

[Maxillary sinus infection with emphysema of the head as a "red herring" in steroid associated colon perforation]. / Kieferhöhleninfekt mit Kopfemphysem als "red herring" bei Steroid-assoziierter Kolonperforation.

Steroid therapy increases the risk of bowel perforation. Bowel perforation may occur at any time of steroid therapy, but the first weeks appear to hold the greatest potential for perforation. However, clinical findings after perforation may be misleading under steroids, and peritonitis may be absent. It is known that bowel perforation can lead to subcutaneous emphysema at various sites. Thus, in any patient with emphysema, bowel perforation must be included in the differential diagnosis, especially in patients receiving steroids. Missing knowledge of this entity may lead to marked delay between onset of initial signs and diagnosis, and hence worsen the survival rate. In this report we present a case of chronic steroid use, where asymptomatic sigma perforation led to a generalized emphysema, which was initially attributed to a maxillary sinus infection due to Aspergillus and anaerobic bacteria.

Modification of a consumer digital audio tape (DAT) for analog data recording.

A modification of a commercially available digital-audio tape (DAT) for DC recordings such as those used in patch clamp and other electrophysiological experiments is introduced. The modified DAT can record data from 2 channels plus a separate trigger signal for up to 2 h. The bandwidth ranges from direct current to 21 kHz; the signal-to-noise ratio is above 90 dB and the A-D resolution is 16 bit. A 120-min cassette yields a storage capacity of 1.4 Gbytes. The trigger is 'hidden' on 1 channel as a burst of 1-ms duration, thus minimizing interference with the recorded data. The modified DAT offers a low-cost yet high quality solution to most analog data storage needs.

Spontaneous recovery from motor asymmetry in adult rats with 6-hydroxydopamine-induced partial lesions of the substantia nigra.

Animals with 6-hydroxydopamine-induced partial unilateral lesions of the substantia nigra exhibit spontaneous recovery from motor asymmetry, a transitory increase in dopamine turnover and an increase in tyrosine hydroxylase activity in the denervated striatum. The recovery of function in these animals seems to be due to the compensatory increase in dopamine metabolism as well as due to the time-dependent increase in tyrosine hydroxylase resulting from either enzyme activation or following reinnervation of the denervated striatum by nigral efferents spared by the partial lesions.

Beta-2-microglobulin--a rapid and automated determination for a broad range of clinical applications.

The clinical evaluation of the Cobas Core beta 2-Microglobulin EIA was performed on the random access analyzer Cobas Core. The coefficients of variations for the intra-assay and inter-assay precisions ranged between 3% and 6%. In comparison to healthy persons (0.7-2.7 mg/l), significantly elevated serum levels of beta 2-m were found in patients with lymphoproliferative disorders like monoclonal gammopathies of the IgG (1.98-78 mg/l; p = 0.0001), IgA (1.3-7.1 mg/l; p = 0.0002) and of the IgM (2.1-8.7 mg/l; p = 0.0001) type, in malignant lymphoma (1.5-33.5 mg/l; p = 0.0001) and in chronic lymphatic leukemia (1.5-22.4 mg/l; p = 0.0001). In cases of HIV-infection, increasing levels of beta 2-m exhibited an inverse correlation to the CD4+ T-lymphocyte count (p = 0.0001) and indicated disease progression. In patients having renal transplantation a rejection of the graft was accompanied by a rise of the beta 2-m serum level. In summary, the data clearly indicate the reliability of the measuring system as well as the clinical relevance of beta-2-M determinations for such patient groups.

Chemotaxis: basic aspects of methodology, mechanisms and pathology.

This review is an attempt to discuss the basic conceptual tools that are a prerequisite for any clinical study of chemotactic defects. They include familiarity with definitions of common terms and with the merits and drawbacks of the several possible in vivo and in vitro assay methods. Cellular mechanisms involved in locomotion are complex. They include basic requirements for cell metabolism as well as receptor recognition, attachment to surfaces and contraction of the cytoskeleton of the cell. Of the many chemotactic factors reported, few are well characterized and universally agreed upon. Similarly, with the use of more stringent criteria, a number of clinical defects of chemotaxis have proven transitory or even artifactual.

Effect of amoxycillin and doxycycline on function of human granulocytes tested in vitro and on chemotaxis of granulocytes from rabbits given the two antibiotics.

The effect of amoxycillin and doxycycline on human granulocyte function was studied in vitro. The antimicrobial agents were added to tests of chemotaxis, random motility, yeast phagocytosis, and killing, at progressing concentrations. The effect was also evaluated in vivo by measuring chemotaxis and random motility (agarose technique) of granulocytes from rabbits injected with these antibiotics. Amoxycillin was shown to have a slightly stimulating effect on chemotaxis, demonstrable only at the highest concentration tested (100 micrograms/ml), and no effect on the other variables. Doxycycline had a dose-related inhibitory effect on chemotaxis, random motility, and phagocytosis, and no effect on killing. Chemotaxis and random motility were slightly, but not significantly, stimulated in vivo when rabbits were given amoxycillin. Chemotaxis (but not random motility) was significantly impaired when the rabbits were given doxycycline.

Evaluation of a new semiquantitative immunodot assay for the screening of specific IgE.

The Immunodot CMG is a new, simple assay for the semiquantitative screening of specific IgE. It does not necessitate any particular equipment. It consists of two nitrocellulose strips on which either five indoor or five outdoor allergens are bound. In the present evaluation, 82 serum samples from allergic patients were tested with the first strip and 101 with the second. The results were compared with those obtained with the CAP System (Kabi Pharmacia). A version using undiluted serum and a short incubation time (short version) appeared to be more sensitive than a long version using serum diluted 1:5. In most cases, the results agreed with those of the CAP System. Discordant results were found in 2-9% of the cases according to the allergen, and were most often negative with Immunodot CMG and positive with the CAP System, indicating a slightly lower sensitivity for the new test. When compared to the CAP System, the Immunodot CMG showed a sensitivity of 84.5% and a specificity of 94%. Readings were found to be reproducible and easy to perform with the naked eye. Our results showed that the Immunodot CMG test is comparable to the CAP System, which is slightly more sensitive but requires much more elaborate and expensive equipment.

The production system and disease incidence in a national random longitudinal study of Swiss dairy herds.

A prospective longitudinal observational study based on a stratified random sample of 113 Swiss dairy farms was conducted between April 1993 and July 1994 with the following objectives: (i) to provide statistically valid estimates of disease frequency in the Swiss dairy cow population, and (ii) to evaluate the feasibility and quality of an intensive farm-based data recording system. During the 15-month study period, farmers were asked to record every health and management event related to their cattle herd. This information was mailed back to the study centre at fortnightly intervals. Additionally, farms were visited regularly to verify received data and to discuss specific problems. During these farm visits, management data were recorded using questionnaires. A complete data set of individual animal events with a total observation time of about 1740 cow-years and 275 calf-years was collected and disease-incidence measures were calculated. The most frequent events were reproductive disorders and udder diseases, followed by lameness and metabolic disorders. Experience with the data collection technique used in this study suggests that a farm-based system is effective and reliable, as long as good contact with the farmers is maintained, and incentives to stimulate their motivation are provided.

[Hepatitis B virus and pathogenesis]. / Hepatitis-B-Virus und Pathogenese.

The hepatitis B virus belongs to the hepadna viruses family. Its genome consists of an incompletely double stranded DNA. The preS/S domain encodes proteins which make up the outer viral coat containing the HBs surface antigen (HBsAg). Other viral genes programme for structures inside the virus and for various regulatory enzymes. HBV mainly infects hepatocytes. The virus replicates in the cytoplasm and is primarily non-cytopathogenic. HBV can also integrate into the host cell. Various stable genotypes and subtypes are known, which have a characteristic geographic distribution. They all share a common HBsAg epitop, which has allowed the development of a vaccine which is efficient world-wide. The protective principle consists of inducing protective anti-HBs. The infected cell has to be destroyed to eliminate the virus. Cellular immune defence mechanisms are mainly relevant, the principle effectors being cytotoxic T lymphocytes, activated monocytes/macrophages and cytokines such as interferon-gamma. The natural course of infection is highly variable, comprising viral elimination with or without acute hepatitis and chronic infection which might lead to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. This is due to the balance respectively to the inbalance between the viral replication capacity and the immune defence mechanisms.

[Serologic diagnosis and follow-up of hepatitis B]. / Serologische Diagnose und Verlaufsbeurteilung der Hepatitis B.

This paper is a short summary on the usefulness of two antigens (HBsAg and HBeAg), three antibodies (anti-HBc, anti-HBe and anti-HBs) and of HBV DNA, as markers for the diagnosis and the follow-up of hepatitis B. The significance of each of these markers at the various stages of disease history, a few patterns of co-existence of some of these markers and the occurrence of mutations in the core and pre-core regions of the genome are also described. The various indications for measuring HBV DNA, in addition to the classical serological markers, are also mentioned.

[Frequency and cost of health problems in Swiss dairy cows and their calves (1993-1994)]. / Häufigkeit und Kosten von Gesundheitsproblemen bei Schweizer Milchkühen und deren Kälbern (1993-1994).

Between July 1993 and July 1994 morbidity and management information related to dairy cows and their calves up to the age of 8 weeks were recorded in 113 randomly selected dairy herds. Also recorded were any costs incurred through disease and prevention. Blood and faeces were analysed with respect to selected pathogens. The health problems most frequently diagnosed in cows were reproductive and udder diseases. Calves suffered most often from diarrhea, omphalitis and pneumonia. The directly disease-related costs per cow-year on average amounted to CHF 139.44 and CHF 4.18 per calf. For prevention, farmers spent on average CHF 10.18 per cow-year. Results from the laboratory analyses indicate that in 68.1% of the farms antibodies against Leptospira hardjo and in 61.9% against Coxiella burnetii were detected. In 8.0% of the farms antibodies against Mycobacterium paratuberculosis were found. Antibodies against BVD virus was present in 99.4% of the farms. Cows from 63.7% farms were infected with gastrointestinal strongylids. Veterinary assistance was required on average 1.96 times per cow-year. In almost all reproductive and puerperal disease cases a veterinarian was consulted while lameness in the majority of cases was treated by the owner. The veterinary profession was hardly ever involved in disease prevention.

Crohn's disease: small bowel motility impairment correlates with inflammatory-related markers C-reactive protein and calprotectin.

BACKGROUND: To evaluate the correlation between the levels of C-reactive protein (CRP), calprotectin, and small bowel motility in patients with Crohn's disease assessed with MRI. METHODS: This prospective institutional review board approved study included magnetic resonance imaging enterography (MRE) and analyses of inflammatory markers in blood (C-reactive protein) and feces (calprotectin). For cine MRE, a coronal 2D-T2w sequence was used on a 1.5 T MRI system. Small bowel motility was analyzed in 13 patients using dedicated magnetic resonance MR-motility assessment software (Motasso). Contraction frequency, amplitude, amplitude diameter ratio, and luminal diameter were determined as well as the blood levels of CRP (mg L(-1) ) and fecal levels of calprotectin (ug g(-1) ). Statistics were calculated using Pearson's correlation coefficient. KEY RESULTS: A significant inverse linear correlation was found between the contraction frequency and both the level of CRP (r = -0.701, P = 0.008) and calprotectin (r = -0.805, P = 0.001). Dilatation of small bowel diameter significantly correlated with calprotectin levels (r = 0.857, P =< 0.001) but not with CRP (r = 0.447, P = 0.126). The absolute amplitude of the contractions did not correlate neither with the level of CRP (r = -0.527, P = 0.064) nor with calprotectin (r = -0.612, P = 0.026). The ratio describing the contraction amplitude relatively to the individual luminal diameter significantly correlated with calprotectin (r = 0.736, P = 0.004) and with CRP (r = 0.577, P = 0.039). CONCLUSIONS & INFERENCES: Alterations of small bowel motility during CD flares significantly correlate with the level of calprotectin and CRP indicating that they represent inflammatory activity.

Pharmacokinetics of cefuroxime in traumatic wound secretion and antibacterial activity under vacuum therapy.

The objective of this study was to investigate the pharmacokinetics of cefuroxime in wound secretion and the antibacterial activity of the traumatic wound secretion in patients receiving cefuroxime and in those not receiving antibiotics. Included in the present controlled, prospective, non-randomized study were 12 patients with an open fracture who needed vacuum therapy (group A) and 12 patients with a closed fracture, who, due to soft tissue damage, also underwent treatment with vacuum therapy (group B). Wound secretion was obtained on the first, third and fifth postoperative days and exposed to the test bacteria, Staphylococcus aureus and Staphylococcus epidermidis. Patients in group A underwent systemic antibiotic treatment with cefuroxime administered intravenously at a dose of 1.5 g every 8 hours. Patients in group B did not receive antibiotics. Cefuroxime concentrations were determined using high-performance liquid chromatography (HPLC). Antibacterial activity was determined using the inhibition test. Maximum cefuroxime concentrations in wound secretion were measured at 4-5 hours following intravenous administration and, with a mean concentration of 10 mg/l, remained consistently above the minimum inhibitory concentration (MIC) for the test bacteria at all points during the measurement period. As expected, the antibacterial activity of the wound secretion in patients in group A (cefuroxime) was higher than that in group B (no antibiotics). In group A, antibacterial activity against S. aureus was 94.6% and 100% against S. epidermidis. In group B, antibacterial activity against S. aureus was 61% and 81% against S. epidermidis. Cefuroxime reaches the highest level in wound secretion after 4 hours. The high antibacterial activity of the wound secretion in traumatic closed fractures is elevated by cefuroxime. in addition, our findings show that vacuum therapy of wounds is suitable as a non-invasive method for studying the pharmacokinetics of antibiotics.