Extensive Bone Marrow Necrosis: A Rare Presentation of Acute Lymphoblastic Leukaemia.

BACKGROUND: Bone marrow necrosis (BMN) is a rare entity which presents with bone pain, fever, and peripheral cytopenia. Acute lymphoblastic leukaemia (ALL) is characterized by malignant proliferation of immature lymphocytes, and patients usually present with fatigue and bleeding manifestations. Presentation with BMN is an extremely rare finding and only few cases had been reported in the literature. Case Presentation. A 22-year-old male presented with nocturnal lower back ache, pleuritic central chest pain, and fever for two weeks. He was extensively investigated for a cause. His investigations revealed pancytopenia with severe neutropenia. Initial bone marrow aspiration and biopsy did not provide a positive result due to extensive necrosis. However, immunohistochemical analysis of few immature lymphoid cells on repeated BM biopsy showed evidence of acute lymphoblastic leukaemia. CONCLUSIONS: ALL usually presents with fatigue and bleeding manifestations. Presentation with BMN is extremely rare. The diagnosis was extremely challenging as this patient had only occasional atypical cells in the peripheral blood film and the repeat bone marrow (BM) biopsy showed extensive necrosis.

Tricuspid Valve Endocarditis due to Streptococcus bovis in a Patient with Ventricular Septal Defect: A Rare Manifestation-Case Report and Review of the Literature.

Streptococcus bovis endocarditis has 18%-62% association with colonic neoplasms with multivalvular involvement and affects mainly elderly males leading to severe cardiac dysfunction, septic embolization, and neurological complications. The aortic valve is the commonest valve to be affected followed by aortic and mitral valves together. However, involvement of tricuspid valve is extremely rare. There are no reported cases of Streptococcus bovis endocarditis affecting the tricuspid valve in the presence of ventricular septal defect with left to right shunt. We report the case of a 25-year-old female with ventricular septal defect who was diagnosed to have tricuspid valve endocarditis caused by Streptococcus bovis. Her detailed colonoscopy, upper gastrointestinal endoscopy, liver biochemistry, and ultrasound scan of the abdomen were normal. She made a very good recovery with six weeks of intravenous antibiotics. This is the first case of tricuspid valve endocarditis caused by Streptococcus bovis in association with ventricular septal defect without any colonic lesions.

Lipopolysaccharide acts synergistically with the dengue virus to induce monocyte production of platelet activating factor and other inflammatory mediators.

BACKGROUND: Platelet Activating Factor (PAF) has been shown to be an important mediator of vascular leak in acute dengue. Antibody dependent enhancement (ADE) and microbial translocation has also shown to contribute to severe dengue. Since monocytes are one of the primary targets of the dengue virus (DENV) we sought to investigate if monocytes were a source of PAF, and the effect of ADE and microbial endotoxin (LPS) on DENV infected monocytes. METHODS: PAF and cytokine levels were evaluated in serial blood samples, in patients with acute dengue infection. The effect of ADE and LPS in production of PAF and cytokines from DENV infected primary human monocytes derived macrophages (MDMθ) was assessed. Gene expression analysis was undertaken to investigate mechanisms by which LPS potentiates PAF and cytokine production by DENV infected MDMθ. RESULTS: Serum PAF levels significantly correlated with both TNF-α (p < 0.0001) and IL-1ß (p < 0.0001) in patients with acute DENV infection. Although primary human MDMθ produced inflammatory cytokines following infection with the DENV, they did not produce PAF following in vitro DENV infection alone, or in the presence of dengue immune serum. Levels of PAF produced by DENV infected MDMθ co-cultured with LPS was significantly higher than uninfected MDMθs co-cultured with LPS. Although TLR-4 was upregulated in uninfected MDMθs co-cultured with LPS, this upregulation was not significant in DENV infected MDMθ. Only expression of RIG-I was significantly up regulated (p < 0.05) when DENV infected MDMθ were co-cultured with LPS. CONCLUSION: LPS acts synergistically with the DENV to induce production of PAF and other inflammatory cytokines, which suggests that microbial translocation that has shown to occur in acute dengue, could contribute to dengue disease severity.

Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.

Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers.