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IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70.

This study was designed to document the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retrospectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are many similarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.

Background: Most studies dealing with vascular response to injury have been conducted using rodent and rabbit models, although it is expected that the response to injury in these species is dissimilar from man., Aims: Here we compare the structure of native carotid artery in rat and baboon and the response of these vessels to endothelial denudation angioplasty., Methods: In both species, the carotid is a musculoelastic artery. Only baboon carotid has a distinct intima, correlating in size with the weight of male baboons. Complete endothelial denudation of left carotid was performed on eight male baboons and 24 male rats by applying an equivalent pull force with a Fogarthy catheter. The animals were sacrificed prior to and 15 min and 2, 3, 4, 7, 14 and 28 days postinjury, one baboon and three rats per time point., Results: Re-endothelialization in the baboon was complete already on day 4, whereas in the rat it was still incomplete on day 28. The proliferative response to injury was far smaller in the baboon than in the rat, the intimal area increased only by 5-fold in baboon compared with 25-fold in rat, and the number of intimal nuclei by 4-fold in baboon compared with 12-fold in rat. Complete compensatory remodelling of the lumen size occurred in the baboon, whereas in the rat remodelling remained incomplete. The cell types participating in the response were, however, similar: deposition of thrombocytes on denuded luminal surface, expression of alpha-actin by intimal cells, and lack of any significant white cell infiltration in the denuded intima., Conclusions: Baboon carotids are very different from rat carotids both in their native structure and in their response to injury. With the limited amount of information available from human vessels, baboon carotids closely resemble human carotids in both respects.

Study Objective: To assess the need for and ability to apply a postnatal assessment protocol (PNAP), consisting of clinical examination, photographs, radiographs, chromosomal analysis and postmortems, of fetuses from mid-pregnancy genetic terminations of pregnancy., Design: Prospective hospital-based study., Setting: The maternity unit at the Pretoria Academic Hospital., Main Results: Fifty consecutively delivered fetuses were assessed by means of the PNAP after genetic termination of pregnancy. A definitive prenatal diagnosis was available in 17 (34%) cases. In 33 (66%) cases the termination was undertaken on the basis of a provisional prenatal diagnosis which was confirmed postnatally in 12 (24%) cases; a definitive postnatal diagnosis could not be confirmed in 5 (10%) cases. In the remaining 16 (32%) cases a totally different postnatal diagnosis was obtained. The definitive postnatal diagnoses in the 28 cases with provisional prenatal diagnoses were confirmed by clinical examination in 13 (26%), by chromosomal analysis in 7 (14%), by postmortem in 5 (10%) and with radiographs in 3 (6%). On retrospective analysis, 22 of the 33 provisional prenatal diagnoses could have been confirmed using available radiographs, chromosome results and photographs only., Conclusions: Genetic terminations of pregnancy are a subgroup of stillbirths for which a PNAP is essential to ensure that appropriate postnatal genetic counselling can be given to the parent(s).

The presence of endotoxin was examined in seven sheep with experimentally induced heartwater. Elevations in endotoxin levels were recorded in one sampling in three of the seven sheep during the acute stage of the disease. The elevations in endotoxin levels were of short duration and decreased in the 24-h follow-up samples. There was no elevation of leukotrienes (B4, C4 and D4) in the blood, or the thoracic or pericardial fluid of any of the sheep.

Studies to evaluate changes in blood clotting, blood calcium and protein, the haematocrit and white-cell counts were undertaken in seven sheep with experimentally induced heartwater. A marked decline in thrombocyte count was recorded during the acute stage of the disease. This was associated with increases in both prothrombin time (PT) and activated partial thromboplastin time (APTT); fibrinogen increased while there was no detectable increase in fibrinogen degradation products (FDP). At the same time total serum protein (TSP), albumin and globulin dropped very sharply; total calcium showed a progressive drop but ionized calcium rose initially and was followed by a terminal decline. The total leucocyte count showed a terminal increase while the haematocrit dropped progressively.

The blood-gas status of seven sheep with experimentally induced heartwater during the acute and terminal stages was investigated. Changes in blood gas included a decline in arterial oxygen tension (pO2) combined with a respiratory alkalosis. Although the sheep became hypoxaemic, blood-gas changes associated with respiratory failure were not observed.