The effects of streptokinase in a Chacma baboon (Papio ursinus) model of acquired thrombotic thrombocytopenic purpura.

TTP is a life-threatening disorder with limited pharmaceutical treatment options. Recently, the potential of streptokinase in the treatment of acquired TTP was demonstrated in humans in vitro, and in vivo in a mouse model. We aimed to determine the in vitro and in vivo effects of streptokinase in an established Papio ursinus model of acquired TTP. In vitro: VWF activities & multimer patterns and thromboelastograms were assessed with increasing concentrations of streptokinase. In vivo: After induction of TTP, escalating streptokinase doses (ranging from 50,000 to 900,000 IU) were administered, and the effects of streptokinase assessed on peripheral blood counts, fibrinolysis, VWF activities & multimer patterns and thromboelastograms. In an extension of the study, high-dose streptokinase (1,500,000-3,000,000 IU) was administered to another baboon. After spiking, fibrinolysis with loss of large VWF multimers was observed at [2200 IU/mL]-roughly equivalent to 1,500,000 IU. However, administration of escalating intravenous streptokinase doses had no in vivo effect on the TTP phenotype, and in vivo increases in plasmin activity were mild when compared with baseline, even at high doses. Minimal effect on VWF multimer patterns was observed but only at doses ≥ 1500,000 IU. Streptokinase is not effective in resolving TTP in a Papio ursinus model of TTP, possibly due to limited activation of the baboon fibrinolytic system. Modifications to this model, the use of alternative higher animal models, or alternative thrombolytics, should be considered to establish proof-of-concept.

Mortality in relation to profiles of clinical features in Ghanaian severely undernourished children aged 0-59 months: an observational study.

Severe acute malnutrition (SAM) is associated with a complex pattern of various clinical conditions. We investigated how risk factors cluster in children with SAM, the relationship between clusters of risk factors and mortality as well as length of stay in children with SAM. A prospective observational study design was used. Data were extracted from medical records of 601 infants and children aged 0-59 months admitted and treated for SAM in three Ghanaian referral hospital between June 2013 and June 2018. Among the 601 medical records extracted, ninety-nine died. Three clusters of medical features clearly emerged from data analyses. Firstly, an association was defined by eye signs, pallor, diarrhoea and vomiting with gastrointestinal infections and malaria. In this cluster, pallor and eye signs were related to 2- to 5-fold increased mortality risk. Secondly, HIV, oedema, fast pulse, respiratory infections and tuberculosis; among those features, HIV increased child mortality risk by 2-fold. Thirdly, shock, convulsions, dermatitis, cold hands and feet, weak pulse, urinary tract infections and irritability were clustered. Among those features, cold hands and feet, dermatitis, convulsions and shock increased child mortality risk in a range of 2- to 9-fold. Medical conditions and clinical signs in children diagnosed with SAM associate in patterns and are related to clinical outcomes.

Vaccine-induced protection against anthrax in cheetah (Acinonyx jubatus) and black rhinoceros (Diceros bicornis).

Institution of a policy of vaccination in endangered species with a vaccine not previously administered to it cannot be undertaken lightly. This applies even more in the case of cheetah (Acinonyx jubatus) with their unusually monomorphic gene pool and the potential restrictions this places on their immune responses. However, the recently observed mortalities from anthrax in these animals in the Etosha National Park, Namibia, made it imperative to evaluate vaccination. Black rhinoceros (Diceros bicornis), another endangered species in the park, have been vaccinated for over three decades but the effectiveness of this has never been evaluated. Passive protection tests in A/J mice using sera from 12 cheetahs together with enzyme immunoassay indicated that cheetah are able to mount seemingly normal primary and secondary humoral immune responses to the Sterne 34F2 live spore livestock vaccine. Overall protection rates in mice injected with the sera rose and fell in concert with rises and declines in antibody titres, although fine analysis showed that the correlation between titre and protection was complex. Once a high level of protection (96% of mice 1 month after a second booster in the cheetahs) had been achieved, the duration of substantial protection appeared good (60% of the mice 5 months after the second booster). Protection conferred on mice by sera from three of four vaccinated rhino was almost complete, but, obscurely, none of the mice receiving serum from the fourth rhino were protected. Sera from three park lions with naturally acquired high antibody titres, included as controls, also conferred high levels of protection. For the purposes of wildlife management, the conclusions were that vaccination of cheetah with the standard animal anthrax vaccine causes no observable ill effect in the animals and does appear to confer protective immunity. At least one well-separated booster does appear to be desirable. Vaccination of rhino also appears to be justified from the limited data obtained.

Left atrial size--a risk factor for left atrial thrombi in mitral stenosis.

In a follow-up study, 77 patients with predominant mitral stenosis were examined to investigate the role of left atrial (LA) enlargement in LA thrombi. Fifteen (19.4%) patients had LA thrombi. Of these, 2 (13.3%) were in sinus rhythm and 13 (86.7%) in atrial fibrillation. Fourteen (93.3%) of the patients with LA thrombi had an LA size > or = 4.8 cm. Only one (6.7%) patient had an LA size of 4.4 cm and was in atrial fibrillation. The median LA size in patients with LA thrombi was 5.2 cm compared with 4.75 cm in patients without LA thrombi (p < 0.01). The relative risk for LA thrombi in patients with an LA size > or = 4.8 cm compared with patients with an LA size < 4.8 cm was 10.0 (95% confidence interval 1.4 to 71.4). It was thus confirmed that LA enlargement > or = 4.8 cm is an independent risk factor for LA thrombi in patients with mitral stenosis.

Echocardiographic study of left atrial thrombi in mitral stenosis.

Sixty-nine patients with predominant mitral stenosis were examined by echocardiographic means to detect the presence of left atrial thrombi. Forty-nine of these patients were in sinus rhythm and twenty in atrial fibrillation. Four percent of patients in the sinus rhythm group and 45% of those in the atrial fibrillation group had left atrial thrombi. The two risk factors identified for left atrial thrombi in mitral stenosis were atrial fibrillation and left atrial enlargement.