Evolution of a fatal septic arthritis caused by a Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus strain

We report the observation of a septic arthritis of the knee complicated within first 36 hours by multiorgan failure including acute respiratory distress syndrome (ARDS), heart failure, acute renal failure and disseminated intravascular coagulation (DIC). A diagnosis of staphylococcal arthritis was suspected confirmed by direct examination, and culture showed a Staphylococcus aureus sensitive to methicillin. The sample sent to the National Reference Centre for Staphylococci (Lyon, France) for genetic analysis confirmed the isolate positive for the PVL gene expression. The fulminating evolution of a septic S. aureus arthritis in an otherwise healthy man should probably evoke the possibility of LPV strain. Anti-PLV antibiotics with anti-staphylococcal activity, such as clindamycin and linezolid should be started without waiting for typing of the S. aureus strain.     

Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.     

Relative contribution of different transmembrane segments to the CFTR chloride channel pore

The membrane-spanning part of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl^? channel comprises 12 transmembrane (TM) α-helices, arranged in 2 symmetrical groups of 6. However, those TMs that line the channel pore are not completely defined. We used patch clamp recording to compare the accessibility of cysteine-reactive reagents to cysteines introduced into different TMs. Several residues in TM11 were accessible to extracellular and/or intracellular cysteine reactive reagents; however, no reactive cysteines were identified in TMs 5 or 11. Two accessible residues in TM11 (T1115C and S1118C) were found to be more readily modified from the extracellular solution in closed channels, but more readily modified from the intracellular solution in open channels, as previously reported for T338C in TM6. However, the effects of mutagenesis at S1118 (TM11) on a range of pore functional properties were relatively minor compared to the large effects of mutagenesis at T338 (TM6). Our results suggest that the CFTR pore is lined by TM11 but not by TM5 or TM7. Comparison with previous works therefore suggests that the pore is lined by TMs 1, 6, 11, and 12, suggesting that the structure of the open channel pore is asymmetric in terms of the contributions of different TMs. Although TMs 6 and 11 appear to undergo similar conformational changes during channel opening and closing, the influence of these two TMs on the functional properties of the narrowest region of the pore is clearly unequal.     

Protective effect of vanillin against carbon tetrachloride (CCl₄)-induced oxidative brain injury in rats

This study investigated the protective effects of vanillin against acute brain damage induced by carbon tetrachloride (CCl?) in rats. The study was performed on 32 male rats divided into four groups: a control group, vanillin group ([Va] 150 mg/kg/day, intraperitoneally [i.p.]) and CCl? toxication groups received a single injection of CCl? (1 ml/kg, i.p.; CCl? and Va + CCl? groups). The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, glutathione transferase, glutathione peroxidase and nitric oxide (NO). Vanillin showed a significant brain-protective effect by decreasing the level of lipid peroxidation and NO? and elevated the activities of antioxidative enzymes and level of GSH. Consequently vanillin blocked oxidative brain damage induced by CCl? in rats.     

Nuclear chemical transformations of ytterbium and lutetium radionuclides following (n,γ) and beta decay reactions in Tris(2,2,6,6-tetramethyle-3,5-heptanedionato)Yb(III)

The behavior of recoiled radionuclides ¹⁶⁹Yb, ¹⁷⁵Yb, and ¹⁷⁷Lu resulting from the reactions ¹⁶⁸Yb(n,γ)¹⁶⁹Yb, ¹⁷⁴Yb(n,γ)¹⁷⁵Yb, and ¹⁷⁶Yb(n,γ)¹⁷⁷Yb→¹⁷⁷Lu, respectively, in the organometallic Tris(2,2,6,6-tetramethyle-3,5-heptanedionato)Yb(III) compound was investigated. Paper chromatography as well as thin layer chromatography, using different patterns of solvents and developers, are discussed. It was found that the organic and inorganic species were of different types and the species resulting from (n,γ) differed from those resulting from β-decay. The species resulting from β-decay reaction were little affected by the type of paper chromatography, while those resulting from (n,γ) reaction were not affected at all. The retention depended on the type of paper and the pattern of solvent/developer. Paper chromatography gave the best results when the compound was dissolved and developed in toluene. The retention values of ¹⁷⁷Lu in three different cases were determined. The obtained retention values indicated that the compound under investigation was not suitable for the purpose of high specific activity radioisotope production.