Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

Successful treatment of invasive pulmonary aspergillosis caused by Aspergillus felis,a cryptic species within the Aspergillus section Fumigati: A case report

Aspergillus species are a major cause of life-threatening infections in immunocompromised hosts, and the most common pathogen of invasive aspergillosis is Aspergillus fumigatus. Recently, the development of molecular identification has revealed cryptic Aspergillus species, and A. felis is one such species within the Aspergillus section Fumigati reported in 2013.We describe a case of invasive pulmonary aspergillosis caused by A. felis in a 41-year-old Japanese woman diagnosed with myelodysplastic syndrome. She presented with fever 19 days after undergoing autologous peripheral blood stem cell transplantation and was clinically diagnosed with invasive pulmonary aspergillosis. Bronchoscopy and bronchoalveolar lavage were performed for definitive diagnosis. The β-tubulin genes of the mold isolated from the bronchoalveolar lavage fluid, and sequenced directly from the PCR products using a primer pair were found to have 100% homology with A. felis. We successfully treated the patient with echinocandin following careful susceptibility testing.To the best of our knowledge, this is the first published case reporting the clinical course for diagnosis and successful treatment of invasive aspergillosis by A. felis.     

Acquisition of antimicrobial-resistant variants in repeated infections caused by Pseudomonas aeruginosa revealed by whole genome sequencing

Pseudomonas aeruginosa, responsible for serious nosocomial-acquired infections, possesses intrinsic antibiotic resistance mechanisms and commonly exhibits multidrug resistance. Here, we report the evolving resistance profiles of strains isolated from the sputum of a patient being treated for repeated P. aeruginosa infections following cancer resection. Whole genome sequencing of six isolates obtained over a 2-month period revealed two key single nucleotide polymorphisms in the mexR and gyrB genes that affected efflux pump expression and antimicrobial resistance.     

Analyses of thrombocytopenia in idiopathic thrombocytopenic purpura-prone mice by platelet transfer experiments between (NZW x BXSB)F1 and normal mice

Male (NZW x BXSB) F1 (W/B F1) mice, which develop lupus nephritis, myocardial infarction, and thrombocytopenia, showed reduced platelet lifespan (PLS) and increased platelet-associated antibody (PAA) values. There were statistically significant correlations between the increase in PAA values and either the reduction in PLS or the decrease in platelet counts. This and the results of platelet transfer experiments between old male W/B F1 mice and either female W/B F1 or normal BALB/c mice indicate that PAAs on the platelet surface play a crucial role in the destruction of platelets in W/B F1 mice. The mechanism of thrombocytopenia observed here appears similar to that of human idiopathic thrombocytopenic purpura (ITP). Therefore, we think that W/B F1 mice are a potentially useful animal model for investigating the effectiveness and mode of action of therapeutic agents in human ITP, and that they may provide additional information on the basic mechanisms of this autoimmune phenomenon.     

Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis

OBJECTIVE: To examine in vivo the effects of a mixture of high molecular weight hyaluronic acid (HA) plus phospholipids on joint lubrication and articular cartilage degeneration. METHODS: Experimental osteoarthritis (OA) of the right knee was induced by anterior cruciate and medial collateral ligament transection in 40 rabbits. The animals were subjected to 8 consecutive weekly intraarticular administrations of high molecular weight HA (the HA200 group), conventional molecular weight HA (the HA80 group), or high molecular weight HA plus L-delta dipalmitoyl phosphatidylcholine liposomes (the PHA group) and were killed 1 week after the final injection. The remaining transected right knees (the OA group) and randomly selected nontransected contralateral left knees (the control group) were collected simultaneously. Each group (n = 10) was divided into 2 equal subgroups, one of which was evaluated histologically while the other was subjected to a lubricating ability test using a pendulum friction tester. RESULTS: The injected knees had a tendency to demonstrate less damage to the articular cartilage compared with the OA group, and the histologic findings in all groups except for the PHA group differed significantly from the control group. There was a significant difference in the mean +/- SD friction coefficient between the control group (0.0100 +/- 0.00300) and the OA (0.0206 +/- 0.00649), HA200 (0.0190 +/- 0.00427), and HA80 (0.0177 +/- 0.00712) groups (P < 0.05 for each comparison), but not between the control group and the PHA group (0.0150 +/- 0.00330) (P = 0.15). CONCLUSION: To our knowledge, this is the first in vivo study to examine whether intraarticular injections of phospholipids influence joint lubrication by acting as a boundary lubricant, thus protecting articular cartilage from degenerative changes.     

Increased gastric acid secretion in cholecystokinin-1 receptor-deficient Otsuka Long-Evans Tokushima fatty rats

BACKGROUND: It is hypothesized that cholecystokinin stimulates acid secretion directly and indirectly by binding to CCK-2 (CCK-B/gastrin) receptors on both parietal and enterochromaffin-like cells. At the same time, however, it inhibits acid responses by stimulating the paracrine secretion of somatostatin from D cells and thereby exerts a tonic inhibition on the parietal cells. To test the validity of this hypothesis, we determined gastric acid secretion in the CCK-1 (CCK-A) receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: Gastric acid secretion was determined in the acute fistula OLETF and the control Long-Evans Tokushima Otsuka (LETO) rats. Plasma concentrations of gastrin, CCK, somatostatin and histamine were determined by radioimmunoassay. The levels of CCK-2 receptor mRNA in the mucosa of the glandular stomach were determined by Northern blot analysis. RESULTS: Pentagastrin- and CCK-8-stimulated as well as basal acid outputs in OLETF rats were significantly higher than those in LETO rats. CCK-2 receptor antagonist reduced basal acid outputs and completely suppressed CCK-8-stimulated acid secretion in both strains. CCK-8 enhanced the pentagastrin-stimulated gastric acid output in OLETF rats, but not in LETO rats. In LETO rats, CCK-1 receptor antagonist increased CCK-8-stimulated gastric acid secretions to those in OLETF rats. The level of CCK-2 receptor mRNA in the stomach in OLETF rats was 2-fold higher than that in LETO rats. In OLETF rats, plasma concentrations of CCK and histamine were higher, whereas somatostatin concentrations were lower than those in LETO rats, with no change in basal plasma gastrin concentrations. CONCLUSIONS: These results in the CCK-1 receptor-deficient OLETF rats confirmed that CCK stimulates acid secretion by binding to CCK-2 receptors, but at the same time inhibits acid responses by stimulating the paracrine secretion of somatostatin from D cells in the gastric mucosa.     

Plasma monocyte chemoattractant protein-1 antigen levels and the risk of restenosis after coronary stent implantation

Monocyte chemoattractant protein-1 (MCP-1) plays a fundamental role in monocyte recruitment and has been implicated in atherosclerosis. The present study tested the hypothesis that increased levels of MCP-1 are associated with an increased risk for restenosis post stent implantation. The plasma MCP-1 antigen levels were measured pre-stenting, and at 24 and 48 h and 6 months post stenting in 41 patients with stable exertional angina (SEA) who had undergone successful stent implantation. Nineteen patients with chest pain syndrome were selected as a control group. Initial plasma MCP-1 antigen levels (mean +/- SE, pg/ml) in the patients with SEA were significantly higher than those in the control group (852.3+/-51.4 vs 418.2+/-26.7, p<0.001). The patients with SEA were divided into 2 groups based on follow-up angiographic findings: 17 patients with restenosis (R group); 24 patients without restenosis (N group). The lesion was significantly longer in the R group than in the N group (p<0.03). Plasma MCP-1 antigen levels at pre-stenting were not significantly different between the 2 groups (820.6+/-69.1 in the R group vs 874.7+/-73.8 in the N group). Serial changes of plasma MCP-1 levels were plotted as percent changes from the initial levels (mean +/- SE, %) and were significantly higher in the R group than in the N group at 48 h and at 6 months post stent implantation (104.6+/-4.8 vs 89.2+/-3.4, p<0.01, 109.6+/-11.2 vs 98.5+/-5.0, p<0.05). The study concludes that MCP-1 production at stented coronary arterial sites is associated with an increased risk for restenosis post stent implantation.