Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies

Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non-inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently replenish the deficient enzyme.

Humoral immune response to ADAMTS13 in acquired thrombotic thrombocytopenic purpura

The apparently spontaneous development of autoantibodies to ADAMTS13 in previously healthy individuals is a major cause of thrombotic thrombocytopenic purpura (TTP). Epitope mapping studies have shown that in most patients antibodies directed towards the spacer domain of ADAMTS13 are present. A single antigenic surface comprising Arg(660) , Tyr(661) and Tyr(665) that contributes to the productive binding of ADAMTS13 to unfolded von Willebrand factor is targeted by anti-spacer domain antibodies. Antibodies directed to the carboxyl-terminal CUB1-2 and TSP2-8 domains have also been observed in the plasma of patients with acquired TTP. As yet it has not been established whether this class of antibodies modulates ADAMTS13 activity. Inspection of the primary sequence of human monoclonal anti-ADAMTS13 antibodies suggests that the variable heavy chain germline gene segment VH1-69 is frequently incorporated. We suggest a model in which 'shape complementarity' between the spacer domain and residues encoded by the VH1-69 gene segment explain the preferential use of this variable heavy chain gene segment. Finally, a model is presented for the development of anti-ADAMTS13 antibodies in previously healthy individuals that incorporates the recent identification of HLA DRB1*11 as a risk factor for acquired TTP.

Hairy pinnae after orchiectomy and chemotherapy for testicular cancer: acquired localized hypertrichosis of the ears

Acquired localized hypertrichosis has rarely been reported. Here, we describe a patient with localized hypertrichosis of the pinnae that occurred 4 months after orchiectomy and chemotherapy for a testicular carcinoma. To our knowledge, this is the first case of an acquired hypertrichosis of the pinnae after cancer therapy. We propose that in our patient either hypogonadism or the hormonal imbalance caused by the cancer therapy led to the development of the hairy pinnae, perhaps alongside a genetic predisposition for hairy ears.

Long-term follow-up of children with acute acquired concomitant esotropia

To study the clinical features and surgical outcome of type 2 (Burian-Franceschetti) acute acquired concomitant esotropia (AACE).

Staphylococcus hyicus bacteremia in a farmer

Bacteria known in animal infectious diseases can cause challenges in human diagnostic laboratories. We present pitfalls in the identification and susceptibility testing of Staphylococcus hyicus, a pathogen that typically causes exudative epidermitis in pigs. In this case, the coagulase-positive staphylococcus isolated from a septic patient was misidentified as Staphylococcus aureus.

Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study

To develop a score predicting the risk of bacteremia in cancer patients with fever and neutropenia (FN), and to evaluate its performance.

The increase of methicillin-resistant Staphylococcus aureus (MRSA) and the presence of an unusual sequence type ST49 in slaughter pigs in Switzerland

Background: In years past, methicillin-resistant S. aureus (MRSA) has been frequently detected in pigs in Europe, North America and Asia. Recent, yet sporadic studies have revealed a low occurrence of MRSA in Switzerland. In 2009, a monitoring survey of the prevalence and genetic diversity of methicillin-resistant S. aureus (MRSA) in slaughter pigs in Switzerland was conducted using methods recommended by the EU guidelines, and using a sampling strategy evenly distributed throughout the year and representative of the Swiss slaughter pig population. Monitoring should determine if the overall prevalence of MRSA in the entire country is increasing over the years and if specific multi-resistant MRSA clones are spreading over the country.;Results: In 2009, the nasal cavities of eight out of 405 randomly selected pigs were positive for MRSA, representing a prevalence of 2.0% (95% CI 0.9-3.9). The following year, 23 out of 392 pigs were positive for MRSA [5.9% prevalence (95% CI 3.8-8.7)]. Three multilocus sequence types (ST), four spa types and two types of staphylococcal cassette chromosome mec (SCCmec) elements were detected. The most frequent genotypes were ST398 (MLST)-(spa)t034-V (SCCmec) (n = 18) and ST49-t208-V (n = 7), followed by ST398-t011-V (n = 4), ST398-t1451-V (n = 1), and ST1-t2279-IVc (n = 1). The isolates displayed resistance to beta-lactams [mecA, (31/31); blaZ, (19/31)]; tetracycline [tet(M), (31/31); tet(K), (30/31)] (n = 31); macrolides and lincosamides [erm(C) (4/31) or erm(A) (18/31)] (n = 22); tiamulin [vga(A)v (9/31) or unknown mechanism (18/31)] (n = 27); trimethoprim [dfr(G) (18/31); spectinomycin [ant(9)-Ia (19/31) or unknown mechanism (3/31)] (n = 22); streptomycin [str(19/31)]; sulphamethoxazole (7/31) and ciprofloxacin (n = 1) (mechanisms not determined).;Conclusions: This study is the first to describe the presence of MRSA ST49 in slaughter pigs, and to demonstrate a significant and nearly three-fold increase of MRSA prevalence in pigs within two years. The presence of a specific clonal lineage of MRSA from Switzerland suggests that it has been selected in Swiss pig husbandry. Effective hygiene measures should be enhanced within the entire pig production chain to suppress the spread of these pathogens into the community.

The word-length effect in acquired alexia, and real and virtual hemianopia

A word-length effect is often described in pure alexia, with reading time proportional to the number of letters in a word. Given the frequent association of right hemianopia with pure alexia, it is uncertain whether and how much of the word-length effect may be attributable to the hemifield loss. To isolate the contribution of the visual field defect, we simulated hemianopia in healthy subjects with a gaze-contingent paradigm during an eye-tracking experiment. We found a minimal word-length effect of 14 ms/letter for full-field viewing, which increased to 38 ms/letter in right hemianopia and to 31 ms/letter in left hemianopia. We found a correlation between mean reading time and the slope of the word-length effect in hemianopic conditions. The 95% upper prediction limits for the word-length effect were 51 ms/letter in subjects with full visual fields and 161 ms/letter with simulated right hemianopia. These limits, which can be considered diagnostic criteria for an alexic word-length effect, were consistent with the reading performance of six patients with diagnoses based independently on perimetric and imaging data: two patients with probable hemianopic dyslexia, and four with alexia and lesions of the left fusiform gyrus, two with and two without hemianopia. Two of these patients also showed reduction of the word-length effect over months, one with and one without a reading rehabilitation program. Our findings clarify the magnitude of the word-length effect that originates from hemianopia alone, and show that the criteria for a word-length effect indicative of alexia differ according to the degree of associated hemifield loss.

Acquired factor XIII deficiency: a therapeutic challenge

Less than 60 cases of acquired factor (F)XIII deficiencies have been reported, most having distinct clinical features. To illustrate the therapeutic challenges of acquired FXIII inhibitors, we report a case of a 65-year-old patient with no previous bleeding history who suddenly developed massive haemorrhages associated to a strong and isolated FXIII inhibitor. No underlying disorder has been detected till now after three years of follow-up. Despite aggressive treatment with prednisone, rituximab, cyclophosphamide, immunoglobulin, immunoadsorption and immune tolerance his inhibitor is still present, although at low titre and with a clinical benefit since the patient has no more bleed since more than one year. Moreover the patient had a venous thromboembolic complication. After a review of the management of acquired FXIII deficiency patients and based on the management of acquired haemophilia we discuss a possible strategy for such difficult cases.

Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study

To examine whether acute dysglycaemia predicts death in people admitted to hospital with community acquired pneumonia.