Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs

Seventy-six dogs with clinical acquired atrioventricular valvular disease were evaluated to determine the efficacy of pimobendan (n=41) versus benazepril hydrochloride (n=35) in a randomized, positive-controlled, multicenter study. The study was divided into 56-day and long-term evaluation periods. In a subgroup of dogs with concurrent furosemide treatment (pimobendan [n=31], benazepril [n=25]), the Heart Insufficiency Score improved in favor of pimobendan (P=0.0011), equating to a superior overall efficacy rating (P<0.0001) at day 56. Long-term median survival (i.e., death or treatment failure) for dogs receiving pimobendan was 415 days versus 128 days for dogs not on pimobendan (P=0.0022).

Reduced perception of the motion-induced blindness illusion in schizophrenia

Motion-induced blindness (MIB) occurs when target stimuli are presented together with a moving distractor pattern. Most observers experience the targets disappearing and reappearing repeatedly for periods of up to several seconds. MIB can be viewed as a striking marker for the organization of cognitive functioning. In the present study, MIB rates and durations were assessed in 34 schizophrenia-spectrum disorder patients and matched controls. The results showed that positive symptoms and excitement enhanced MIB, whereas depression and negative symptoms attenuated the illusion. MIB was more frequently found in normal subjects. The results remained consistent after adjusting for reaction time and error rates. Hence, MIB may provide a valid and reliable measure of cognitive organization in schizophrenia.

Multiple B-cell clones producing antibodies directed to the spacer and disintegrin/thrombospondin type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with acquired thrombotic thrombocytopenic purpura

BACKGROUND: The cysteine-rich/spacer domains of ADAMTS13 contain a major binding site for antibodies in patients with acquired thrombotic thrombocytopenic purpura (TTP). OBJECTIVE: To study the heterogeneity of the antibody response towards these domains an immunoglobulin V-gene phage-display library was constructed to isolate monoclonal anti-ADAMTS13 antibodies from the immunoglobulin repertoire of a patient with acquired TTP. METHODS: Combined variable heavy chain (VH) and variable light chain (VL) segments, expressed as single-chain Fv fragments (scFv), were selected for binding to an ADAMTS13 fragment consisting of the disintegrin/thrombospondin type-1 repeat 1 (TSP1)/cysteine-rich/spacer domains. RESULTS: Seven different scFv antibody clones were identified that were assigned to four groups based on their homology to VH germline gene segments. Epitope-mapping revealed that scFv I-9 (VH1-69), I-26 (VH1-02), and I-41 (VH3-09) bind to an overlapping binding site in the ADAMTS13 spacer domain, whereas scFv I-16 (VH3-07) binds to the disintegrin/TSP1 domains. The affinity of scFv for the disintegrin/TSP1/cysteine-rich/spacer domain was determined by surface plasmon resonance analysis and the dissociation constants ranged from 3 to 254 nM. The scFv partially inhibited ADAMTS13 activity. However, full-length IgG prepared from the variable domains of scFv I-9 inhibited ADAMTS13 activity more profoundly. Plasma of six patients with acquired TTP competed for binding of scFv I-9 to ADAMTS13. CONCLUSION: Our data indicate that multiple B-cell clones producing antibodies directed against the spacer domain are present in the patient analyzed in this study. Our findings also suggest that antibodies with a similar epitope specificity as scFv I-9 are present in plasma of other patients with acquired TTP.

[Community-acquired pneumonia--pathogens and assessment]

Pneumonia is one of the most important infectious diseases, both in terms of incidence as well as potential severity. Streptococcus pneumoniae remains the most prevalent etiologic agent, accounting for about two-thirds of bacteremic cases. Diagnostic procedures include chest radiography, blood culture, Gram staining and culture of expectorated sputum, urine antigen assays for Legionella pneumophila and pneumococci, and asservation of an initial serum sample for comparative serologic investigations. Molecular biology techniques continue to gain importance for the diagnosis of Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionellae and viral respiratory infections, however, their availability at present is mainly restricted to research and reference laboratories.

"HIT on Trousseau" double trouble: acquired coagulopathy with femoral artery thrombosis

Trousseau Syndrome is a paraneoplastic procoagulant phenomenon. Heparin-induced thrombocytopenia (HIT) is a rare complication of anticoagulation with heparin. To our knowledge, the coincidence of the two has not been reported so far. We report a case of an acute thrombosis of the left femoral artery and distal leg arteries in a patient with an otherwise normal cardiovascular status. Endovascular revascularization attempts using mechanical rotational thrombectomy catheter, aspiration and local thrombolysis were unsuccessful. Progressive coagulation along the intra-arterial catheter was seen. Surgical thrombectomy of the femoral-pedal axis was successful, but the patient developed an immune-mediated HIT postoperatively. An adenocarcinoma of the colon was the likely cause for the initial arterial thrombosis, and probably adversely affected endovascular revascularization attempts. Subsequent HIT with microvascular thrombosis worsened ischemic damage leading to a below knee-amputation, despite patent large vessels. Compared to venous thrombosis, arterial thrombosis is a rare manifestation of Trousseau syndrome. The coincidence of it with HIT is even rarer. There may be a causal relationship between the two.

Susceptibility of Escherichia coli strains isolated from outpatient children with community-acquired urinary tract infection in southern Switzerland

BACKGROUND: Based on antimicrobial resistance patterns found in Swiss university hospitals, treatment with a third-generation cephalosporin is currently advised for Swiss children with urinary tract infection. OBJECTIVE: The aim of this study was to prospectively assess the susceptibility of Escherichia coli strains isolated from children with symptomatic community-acquired urinary tract infection. METHODS: The antimicrobial susceptibility of E coli strains causing symptomatic community-acquired urinary tract infections was assessed in outpatient children attending the emergency management unit at the Department of Pediatrics, Mendrisio and Bellinzona Hospitals, Switzerland. Strains from children receiving antimicrobial prophylaxis or prescribed antimicrobials in the previous 4 weeks were excluded. Clinical and Laboratory Standards Institute methods were used for culture and identification of pathogens. E coli susceptibility testing was performed using the disk diffusion technique. RESULTS: Strains from 100 consecutive outpatient children (73 girls, 27 boys; aged 5 weeks-17 years [median, 33 months]; 100% white) were assessed. High rates of ampicillin and cotrimoxazole resistance (39 and 21 strains, respectively) and low rates of nitrofurantoin resistance (4 strains) were identified. No resistance was identified for coamoxiclav or third-generation cephalosporins. CONCLUSIONS: In these Swiss outpatient children with symptomatic community-acquired urinary tract infection, without antimicrobial prophylaxis or recent prescription of antimicrobials, uropathogenic E coli strains resistant in vitro to ampicillin and cotrimoxazole were common. However, in vitro resistance to nitrofurantoin, coamoxiclav, and third-generation cephalosporins was uncommon.

Immunosuppressive treatment for acquired haemophilia: current practice and future directions in Germany, Austria and Switzerland

Acquired haemophilia is an autoimmune disorder characterised by autoantibody formation against coagulation factor VIII. Immunosuppressive treatments including steroids, cytotoxic drugs, rituximab or combinations thereof have been used to eradicate autoantibodies. Very few prospective studies exist evaluating the use of these treatments. Here, we performed a survey among 73 physicians from 57 haemophilia treatment centres in order to describe current practice patterns and critical issues for future research in acquired haemophilia. The results demonstrate a high diversity of first- and second-line treatments. Factors influencing treatment decision were underlying disorder, severity of bleeding and inhibitor titre. Frequently used first-line treatments were steroids plus cyclophosphamide (44%) and steroids alone (11%). Second-line treatment was most often rituximab (30%), with or without steroids and/or cyclophosphamide. Most participants indicated to change from first- to second-line treatment after 4 weeks in case of failure to obtain partial remission (31%), continued bleeding (40%) or continued severe bleeding requiring bypass treatment (59%). Immunoadsorption was preferred for first- and second-line treatment by 10% and 9% of participants, respectively. These results highlight critical issues in the field. Open questions and directions for future research are discussed.

IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura

BACKGROUND: ADAMTS13-neutralizing IgG autoantibodies are the major cause of acquired thrombotic thrombocytopenic purpura (TTP). OBJECTIVE: To analyze the IgG subclass distribution of anti-ADAMTS13 antibodies and a potential relationship between subclass distribution and disease prognosis. METHODOLOGY: An enzyme-linked immunosorbent assay-based method was used to quantify the relative amounts of IgG subclasses of anti-ADAMTS13 antibodies in acquired TTP plasma. RESULTS: IgG(4) (52/58, 90%) was the most prevalent IgG subclass in patients with acquired TTP, followed by IgG(1) (52%), IgG(2) (50%), and IgG(3) (33%). IgG(4) was found either alone (17/52) or with other IgG subclasses (35/52). IgG(4) was not detected in 10% of the patients. There was an inverse correlation between the frequency and abundance of IgG(4) and IgG(1) antibodies (P < 0.01). Patients with high IgG(4) levels and undetectable IgG(1) are more prone to relapse than patients with low IgG(4) levels and detectable IgG(1). CONCLUSIONS: All IgG subclasses of anti-ADAMTS13 antibodies were detected in patients with acquired TTP, with IgG(4), followed by IgG(1), antibodies dominating the anti-ADAMTS13 immune response. Levels of IgG(4) could be useful for the identification of patients at risk of disease recurrence.

VH1-69 germline encoded antibodies directed towards ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura

BACKGROUND: Autoantibodies directed towards ADAMTS13 are present in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). Analysis of a set of antibodies derived from two patients with acquired TTP revealed frequent use of the VH1-69 heavy chain gene segment for the assembly of anti-ADAMTS13 antibodies. OBJECTIVE: We explored the ability of two VH1-69 germline gene-encoded antibodies to inhibit the von Willebrand factor (VWF)-processing activity of ADAMTS13 under different experimental conditions. Furthermore, the presence of VH1-69 encoded anti-ADAMTS13 antibodies in 40 patients with acquired TTP was monitored using monoclonal antibody G8, which specifically reacts with an idiotype expressed on VH1-69 encoded antibodies. METHODS AND RESULTS: Binding of the two VH1-69 encoded monoclonal antibodies was dependent on the presence of the spacer domain. Both antibodies inhibited ADAMTS13 activity under static conditions, as measured by cleavage of FRETS-VWF73 substrate and cleavage of VWF multimers. The recombinant antibodies were also capable of inhibiting the processing of UL-VWF strings on the surface of endothelial cells. G8-reactive antibodies directed towards ADAMTS13 were present in plasma of all patients containing anti ADAMTS13 antibodies. CONCLUSIONS: These results suggest that VH1-69 derived antibodies directed towards ADAMTS13 develop in the majority of patients with acquired TTP.

Toltrazuril treatment of congenitally acquired Neospora caninum infection in newborn mice

C57BL/6 mice were infected with Neospora caninum tachyzoites during pregnancy, yielding a transplacental infection of developing fetuses. Subsequently, congenitally infected newborn mice were treated either once or three times with toltrazuril (or placebo) at a concentration of 31.25 mg compound per kg body weight. Both toltrazuril and placebo treatment had no negative effect on newborns, as noninfected treated pups developed normally without differences in mortality and morbidity to matching nontreated control animals. Already one application of toltrazuril was significantly (p < 0.01) able to delay the outbreak of neosporosis in newborn mice, when compared to placebo-treated infected controls. We found significantly higher proportion of surviving newborns in one-time-toltrazuril-treated and three-time-toltrazuril-treated groups (34% and 54%, respectively) when compared to one-time-placebo-treated and three-time-placebo-treated groups (14% and 30%, respectively). There was no significant difference (p = 0.2) in the proportion of surviving pups between one-time-toltrazuril and three-time-toltrazuril treatment. However, the number of diseased and Neospora-positive pups (46% and 47%, respectively) was markedly reduced after three-time-toltrazuril treatment compared to all other groups. Three-time-treatment also resulted in the highest antibody (IgG, IgG2a) response. Pharmacokinetic analyses using individual serum samples revealed that, although toltrazuril was absorbed and metabolized to toltrazuril sulfone by newborn mice, medicated animals exhibited an unexpected rapid turn-over (half-life time) of the compound. Toltrazuril and the metabolite were also found in brain tissues, indicating that passage of the blood-brain barrier occurred. In conclusion, we could show that three times treatment with toltrazuril had a high impact on the course of infection in congenitally N. caninum-infected newborn mice.

Fatal aortic endocarditis associated with community-acquired Serratia marcescens infection in a dog

A 12 yr old Dalmatian was referred for evaluation of acute lethargy, fever, neurologic signs, and a recently ausculted heart murmur. Echocardiography in combination with blood cultures resulted in a diagnosis of nonhospital-acquired Serratia marcescens bacteremia and aortic valve endocarditis. Despite early diagnosis and aggressive therapy, the dog failed to respond to antimicrobials and died within 6 hr after admission. Necropsy findings included aortic valve endocarditis, septicemia, and diffuse thromboembolic disease. There was no history of pre-existing underlying disease or immunosuppressive therapy, and the dog had not been hospitalized before referral.