Toll-like 4 receptor variant, Asp299Gly, and reduced risk of hemorrhagic cystitis after hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a major cause of morbidity after hematopoietic stem cell transplantation. Toll-like receptor 4 (TLR4) is a pattern recognition receptor of the innate immune system and induces inflammation. Individuals with the single nucleotide polymorphisms Thr399Ile (rs4986791) or Asp299Gly (rs4986790) of TLR4 show diminished inflammatory responsiveness to endotoxins. The genotype of TLR4 was determined in 166 children who underwent allogeneic hematopoietic stem cell transplantation and in their donors. Asp299Gly was present in 21 patients (13%) and 24 donors (14%). Thr399Ile was found in 22 patients (13%) and 25 donors (15%). The incidence of HC was significantly lower in patients with Asp299Gly (0% vs 23%; P = .009) and in patients who underwent transplantation from a donor with Asp299Gly (4% vs 23%; P = .05). The trend was the same for Thr399Ile-donor positive (8% vs 22%; P = .17), recipient positive (9% vs 22%; P = .25), donor or recipient positive (8% vs 23%; P = .04). Multivariate analysis revealed age, conditioning with busulfan, and absence of Asp299Gly as independent risk factors for HC. In conclusion, the TLR4 Asp299Gly variant seems to confer protection against hemorrhagic cystitis. This study provides the first indication that the innate immune system through TLR4 signaling pathway plays a role in the pathogenesis of HC after hematopoietic stem cell transplantation.

Fibrinogenolytic and procoagulant activities in the hemorrhagic syndrome caused by Lonomia obliqua caterpillars.

The hemorrhagic syndrome caused by accidents with caterpillars of the genus Lonomia has been the focus of several clinical and biochemical studies, since its venom is composed of many active principles that interfere with the hemostatic system. Whereas a fibrinolytic agent has been characterized in the venom of Lonomia achelous, in Lonomia obliqua, only a prothrombin activator activity has been reported so far, even though both species cause similar bleeding disorders, characterized by hemorrhage, disseminated intravascular coagulation (DIC), and acute renal failure. Considering the possibility that the hemorrhagic syndrome resulting from envenoming by L. obliqua may be due to fibrinolytic and procoagulant activities acting together, we decided to investigate the effects of bristle extract (BE) of this species upon blood coagulation and fibrin(ogen)olysis. This study shows that besides a procoagulant activity related to the activation of prothrombin, the venom contains at least one fibrin(ogen)olytic activity, as shown by fibrinolysis in a fibrin (F) plate assay, by interference in thrombin-catalyzed fibrinocoagulation, and by polyacrylamide gel electrophoresis profile of fibrin and fibrinogen (Fg) degradation. Considering that a recombinant prothrombin activator from L. obliqua has been suggested in other studies to be used as an anti-thrombotic agent, it is important in the first place to better characterize the different active principles of this venom.

Percutaneous drainage of liver abscess complicated by hepato-venous fistula.

Severe systemic sepsis after percutaneous drainage of liver abscess is rare. We report two cases of hepato-venous fistulas between hepatic abscesses and hepatic/portal veins documented on abscessography during percutaneous drainage of liver abscesses, which resulted in severe sepsis and a stormy post drainage clinical course. Liver abscesses can rupture into the portal and hepatic veins causing worsening of systemic sepsis especially when they are in close proximity to each other. During percutaneous drainage, care must also be taken to avoid overinjection of the abscess, which can worsen the fistula. The ensuing sepsis is severe and requires aggressive intensive medical care and ventilatory support to tide the patient over the septic episode.

Aislamiento de Aeromona hydrophila en trucha Arcoiris (Oncorhynchus mykiss) / Isolation of Aeromona hydrophila in rainbow trowt (Oncorhynchus mykiss). Case report

Se realizó un muestreo en una granja piscícola dedicada a la explotación de trucha Arcoiris (Oncorhynchus mykiss), ubicada en el Estado de México, México, en el cual hubo un brote de septicemia hemorrágica provocada por el agente etiológico Aeromona hydrophila. Los animales presentaban oscurecimeinto de la piel, exoftalmina unilateral y el patrón de comportamiento alterado, la morbilidad fue del 80 por ciento y la mortalidad del 51.2 por ciento. Se llevaron a cabo estudios de histopatología y se encontró lesiones en intestino anterior, con hiperplasia del epitelio de las vellosidades, En encéfalo (cerebro medio) hubo congestión leptomeningea moderada difusa y en ojo se apreciaron focos de trombosis y reacción inflamatoria constituida por monocitos en la región periesclerótica y epitelio corneal. Se realizó estudio bacteriológico a partir del hígado de truchas Arcoiris afectadas, de donde se aisló A. hydrophilia, corroborándose las lesiones y el cuadro clínico antes descritos con la presencia del agente

REP-PCR analysis of Pasteurella multocida isolates that cause haemorrhagic septicaemia.

Amplification of multiple P multocida genomic DNA fragments by outwardly-directed primers based on the repetitive extragenic palindromic (REP) consensus sequence, generated complex profiles in a PCR-based fingerprinting method known as REP-PCR. Polymorphisms within REP-PCR profiles were used to characterise 38 isolates of P multocida. The high degree of homogeneity observed among haemorrhagic septicaemia (HS) strains of serotype B and E provided evidence of a disease-associated REP profile that may serve as a novel method for the identification of HS strains regardless of serotype. REP-PCR profiles of other P multocida serotypes were highly variable, illustrating the potential of this technique for the molecular fingerprinting of fowl cholera or atrophic rhinitis isolates. A specific amplified REP fragment was isolated and used to probe membrane-bound digested P multocida genomic DNA. Hybridisation patterns not only distinguished HS-causing isolates from non-HS P multocida, but also demonstrated a degree of relatedness between HS and HS-like strains.

Vacuolating cytotoxic activity of Pasteurella multocida causing haemorrhagic septicaemia in buffalo and cattle.

The toxic activity of Pasteurella multocida strains which cause haemorrhagic septicaemia (HS) in buffalo and cattle was examined in a mouse model. Mice were injected intraperitoneally with 10(2) cells of P. multocida serotype B:2,5. Electron microscopy of peritoneal macrophages obtained 6 h after injection revealed strong induction of cytoplasmic vacuolation, macrophage lysis and death. In vitro experiments with the mouse macrophage cell line RAW 264 incubated with cultures of various HS- and non-HS-associated strains of P. multocida or with culture supernatants revealed macrophage vacuolation when HS-associated strains were used. On pre-incubation of the strains with antiserum obtained from buffalo infected with P. multocida serotype B:2,5 no vacuolation was observed. These results are indicative of the presence of vacuolating cytotoxic activity in HS-associated strains of P. multocida.

Persistence of the carrier status in haemorrhagic septicaemia (Pasteurella multocida serotype 6:B infection) in buffaloes.

Fifty-seven young buffaloes were experimentally infected or naturally exposed to haemorrhagic septicaemia (HS). Of these animals 32 became immune carriers. They were observed in groups for periods up to 360 days to monitor the appearance of pasteurellae in the nasopharynx and antibody status. In most animals pasteurellae appeared in the nasopharynx for a short period initially and disappeared. The organism reappeared intermittently and the longest observed period of reappearance was 215 days after exposure. All animals showed rising antibody titres with a peak lasting for 150 to 180 days and declining thereafter. Pasteurellae persisted in the tonsils and were isolated from 20 out of 27 carriers after slaughter. The longest period when isolation was made after slaughter was 229 days. The organism lodged in the tonsils was unaffected by antibacterial therapy using drugs to which the organism displayed in vitro sensitivity. It is concluded that in HS, carrier animals exist in an active as well as a latent state, the former appearing for short intermittent periods between long latent periods, when pasteurellae continue to remain in the tonsils which constitute a long-term reservoir.

[The etiology of liver dystrophy in the field hare (Lepus europaeus pallas)]. / Untersuchungen zur Atiologie der Leberdystrophie des Feldhasen (Lepus europaeus pallas).

The liver dystrophy of the European Brown Hare is widely distributed in Europe and predominantly called European Brown Hare Syndrome (EBHS) or Hemorrhagic Septicemia Syndrome. The disease could be reproduced by injection of sterile filtered organ material of two field cases in two hares held in captivity. The clinical symptoms and the pathologic alterations are described.