Culture-negative bivalvular endocarditis with myocardial destruction in a patient with systemic lupus erythematosus: a case report

Culture-negative endocarditis has long been associated with systemic lupus erythematosus, but is usually asymptomatic or involves a single valve. We present a patient with destructive culture-negative endocarditis that remains without a microbial etiology despite an exhaustive workup using advanced diagnostic techniques in a patient with systemic lupus erythematosus

The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions

Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11).

Contains fulltext : 81619.pdf (publisher's version ) (Open Access)BACKGROUND: The treatment of patients with haematological malignancies by means of haematopoietic stem cell transplantation (HSCT) is often accompanied by life threatening infections. With emerging antimicrobial resistance there is an increased need for new agents, with a beneficial safety profile. Therefore we evaluated the safety of the promising new antimicrobial peptide human lactoferrrin 1-11 (hLF1-11) in healthy volunteers and patients. METHODS: We undertook a sequential, randomised, double-blind, placebo-controlled study using ascending single (0.005, 0.05, 0.5, 5 mg) and multiple intravenous doses (0.5, 5 mg) in healthy volunteers, and open-label, single intravenous 5 mg doses in autologous HSCT recipients. Results : Single and multiple doses of hLF1-11 were tolerable up to 5 mg intravenously in healthy volunteers, while 5 mg single dose was tolerable in patients. Elevations in transaminases possibly related to treatment were reversible and not serious. CONCLUSION: The new antimicrobial hLF1-11 is well tolerated in healthy volunteers with repeated daily doses up to 5 mg. The side-effect profile is very favourable for an antimicrobial, the only undesirable effect being a possible elevation of transaminases, which may be related to hLF1-11 although the current data do not allow conclusive interpretation of treatment relationship. A lower dose is recommended for the forthcoming multiple dosing studies in HSCT patients. TRIAL REGISTRATION: ClinicalTrials.gov: nct00509938

Cancer survival in Indigenous and non-Indigenous Australian children: what is the difference?

Purpose: This study assessed variation in childhood cancer survival by Indigenous status in Australia, and explored the effect of place of residence and socio-economic disadvantage on survival. Methods: All children diagnosed with cancer during 1997-2007 were identified through the Australian Pediatric Cancer Registry. Cox regression analysis was used to assess the adjusted differences in survival. Results: Overall, 5-years survival was 75.0 % for Indigenous children (n = 196) and 82.3 % for non-Indigenous children (n = 6,376, p = 0.008). Compared to other children, Indigenous cases had 1.36 times the risk of dying within 5 years of diagnosis after adjustments for rurality of residence, socio-economic disadvantage, cancer diagnostic group, and year of diagnosis (95 % CI 1.01-1.82). No significant survival differential was found for leukemias or tumors of the central nervous system; Indigenous children were 1.83 times more likely (95 % CI 1.22-2.74) than other children to die within 5 years from 'other tumors' (e.g., lymphomas, neuroblastoma). Among children who lived in 'remote/very remote/outer regional' areas, and among children with a subgroup of 'other tumors' that were staged, being Indigenous significantly increased the likelihood of death (HR = 1.69, 95 % CI 1.10-2.59 and HR = 2.99, 95 % CI 1.35-6.62, respectively); no significant differences by Indigenous status were seen among children with stage data missing. Conclusions: Differences in place of residence, socio-economic disadvantage, and cancer diagnostic group only partially explain the survival disadvantage of Indigenous children. Other reasons underlying the disparities in childhood cancer outcomes by Indigenous status are yet to be determined, but may involve factors such as differences in treatment