Multispacer typing of Rickettsia prowazekii enabling epidemiological studies of epidemic typhus

Currently, there is no tool for typing Rickettsia prowazekii, the causative agent of epidemic typhus, currently considered a potential bioterrorism agent, at the strain level. To test if the multispacer typing (MST) method could differentiate strains of R. prowazekii, we amplified and sequenced the 25 most variable intergenic spacers between the R. prowazekii and R. conorii genomes in five strains and 10 body louse amplicons of R. prowazekii from various geographic origins. Two intergenic spacers, i.e., rpmE/tRNA(fMet) and serS/virB4, were variable among tested R. prowazekii isolates and allowed identification of three and two genotypes, respectively. When the genotypes obtained from the two spacers were combined, we identified four different genotypes. MST demonstrated that several R. prowazekii strains circulated in human body lice during an outbreak of epidemic typhus in Burundi. This may help to discriminate between natural and intentional outbreaks. Our study supports the usefulness of MST as a versatile method for rickettsial strain genotyping.     

Cariporide对兔心房电重构的影响

目的：探讨钠氢交换体Ⅰ型(NHE-1)特异性抑制剂cariporide对快速起搏所致兔心房电重构的影响。 方法： 30只兔随机等分为3组：对照组、起搏组和cariporide组。起搏组和cariporide组给予6 h 600 beats/min的快速心房起搏。测定各组不同时点的心房有效不应期（AERP200，AERP150，AERP130），连续刺激6 h后取左右心耳组织，用Western blotting测定NHE-1的含量。 结果： 在快速起搏后1 h后，起搏组的AERP200较起搏前明显缩短，2 h时达高峰，相对缩短量为（15.63±9.04）ms，而对照组和cariporide组AERP未发生明显变化，起搏2h时相对缩短量为(1.43±2.44)ms和(1.43±6.90)ms（P<0.05，与起搏组相比），这些变化一直保持至快速起搏后6 h；起搏组的AERP频率适应性下降, 起搏前AERP130较AERP200缩短(11.88±15.57)ms，起搏后6 h只缩短(4.38±5.63)ms。而cariporide组的AERP频率适应性则未发生显著变化。起搏组右心耳组织的NHE-1含量显著少于对照组（P<0.05），cariporide组的右心耳组织NHE-1含量与对照组差异不显著。 结论： Cariporide可有效阻止快速心房起搏引起的AERP缩短，但不影响起搏引起的NHE-1含量的下降。     

新生儿缺氧、缺血性脑病血中6-keto-PGF1α,NSE水平变化的临床研究

目的:探讨HIE患者血中6-keto-PGF1α、NSE水平变化及临床意义.方法:用RIA检测89例HIE患者和32例正常新生儿血中6-keto-PGF1α、NSE水平变化.结果:HIE轻、中、重度组6-keto-PGF1α水平与正常对照组比较,均存在显著性差异(p＜0.01),HIE患者轻度组NSE水平与对照组比较无显著性差异(p＞0.05),中、重度组NSE水平与对照组比较存在显著性差异(p＜0.01),6-keto-PGF1α、NSE二组血中浓度上升与HIE程度呈正相关.结论:HIE患者中6-keto-PGF1α、NSE水平检测,对判断HIE的脑损伤程度、治疗、预后观察,具有重要临床意义和应用价值.     

Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab.

Adenoviruses are emerging as a major cause of infectious complications after allogeneic transplantation. We evaluated the incidence and outcome of symptomatic adenovirus infection or adenovirus disease after alemtuzumab-based reduced-intensity conditioning in 86 consecutive patients. The overall probability of adenovirus disease was 18.4% (11/86 patients). Five patients died of progressive adenovirus disease, and this was the most important infectious cause of mortality in this cohort. The probability of nonrelapse mortality was 49% in patients with adenovirus disease compared with 25.5% in those without (P=.007). The severity of lymphocytopenia and continuation of immunosuppressive therapy were the most important risk factors for progressive adenovirus disease and death. In contrast, patients who were not receiving immunosuppressive therapy or had had it reduced or withdrawn cleared the virus. We also detected a correlation between the lack of preemptive anti-cytomegalovirus (CMV) therapy for CMV reactivation and the risk of progressive adenovirus disease (P=.05). Our findings highlight the emergence of adenovirus as an important posttransplantation pathogen even after reduced-intensity conditioning and demonstrate the effect of the severity of lymphocytopenia, anti-CMV prophylaxis, and immunosuppressive therapy on the outcome of adenovirus disease.     

Reconstitution of T-cell repertoire after autologous stem cell transplantation: influence of CD34 selection and cytomegalovirus infection.

The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor beta-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation (P =.08) that became significant by 3 months (P=.007), and that was associated with decreased T-cell receptor beta-chain variable region spectratype diversity (P =.01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution.     

A case of multiple schwannomas of the trigeminal nerves, acoustic nerves, lower cranial nerves, brachial plexuses and spinal canal: schwannomatosis or neurofibromatosis?

In most cases, while schwannoma is sporadically manifested as a single benign neoplasm, the presence of multiple schwannomas in one patient is usually indicative of neurofibromatosis 2. However, several recent reports have suggested that schwannomatosis itself may also be a distinct clinical entity. This study examines an extremely rare case of probable schwannomatosis associated with intracranial, intraspinal and peripheral involvements. A 63-year-old woman presented with a seven-year history of palpable lumps on both sides of the supraclavicular area and hearing impairment in both ears. On physical examination, no skin manifestations were evident. Facial sensory change, deafness in the left ear and decreased gag reflex were revealed by neurological examination. Magnetic resonance imaging revealed multiple lesions of the trigeminal nerves, acoustic nerves, lower cranial nerves, spinal accessory nerve, brachial plexuses, and spinal nerves. Pathological examination of tumors from the bilateral brachial plexuses, the spinal nerve in the T8 spinal position and the neck mass revealed benign schwannomas. Following is this patient case report of multiple schwannomas presenting with no skin manifestations of neurofibromatosis.     

The effect of beta adrenergic stimulation on QT and QTc interval in syncope children with or without coexisting ventricular arrhythmias

We investigated the effect of beta-adrenergic stimulation on the heart rate and QT interval in syncope children with or without coexisting ventricular arrhythmias (VA). Of the 24 children who presented with syncope or presyncope and showed negative tilt test, 13 were classified into a group with VA and the remaining 11 without VA. The provocative test was performed in bolus infusion and continuous infusion. RR, QT, and QTc intervals on routine 12-lead surface electrocardiogram were obtained during each stage of isoproterenol infusion. In all cases, malignant ventricular arrhythmia and syncope were not induced by isoproterenol provocative test. RR and QT intervals were shortened and QTc intervals were prolonged as the isoproterenol dose was increased in both groups and methods. The QTc interval reached its peak level after the bolus injection of 1.0 microgram and during the continuous infusion of 0.03 microgram/kg/min. The two groups showed no significant difference in the QTc interval change according to the infusion methods. This study indicates that changes in the heart rate and QT interval by beta-adrenergic stimulation were not different according to the coexisting ventricular arrhythmias in syncope children with negative head-up tilt test.     

Emergence and wide dissemination of CTX-M-type ESBLs, and CMY-2- and DHA-1-type AmpC beta-lactamases in Korean respiratory isolates of Klebsiella pneumoniae

Respiratory isolates of Klebsiella pneumoniae in Korea during 2002-2003 were studied to determine the prevalence and types of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated AmpC beta-lactamases (PABLs). ESBL-production was tested by double-disk synergy, and genotypes of beta-lactamases were determined by PCR and sequencing. ESBLs were detected in 28.4% of 373 isolates, and the most prevalent types were SHV-12 (63 isolates) and CTX-M-14 (9 isolates). Forty of 75 ESBL-producers (53.5%) also had PABLs: 21 isolates with CMY-2-like, 17 with DHA-1-like. Pulsed-field gel electrophoresis showed 19 types and 25 of 74 isolates had an identical pattern, indicating nosocomial spread. Dissemination of ESBL- and PABL-producing K. pneumoniae strains in Korea is a particular concern, as it limits the choice of antimicrobial agents for treatment of infections.     

Differentiation of muscle-derived cells into myofibroblasts in injured skeletal muscle

Injured muscle can initiate regeneration promptly by activating myogenic cells that proliferate and differentiate into myotubes and myofibers. However, the recovery of the injured skeletal muscle often is hindered by the development of fibrosis. We hypothesized that the early-appearing myogenic cells in the injured area differentiate into myofibroblasts and eventually contribute to the development of fibrosis. To investigate this, we transplanted a genetically engineered clonal population of muscle-derived stem cells (MC13 cells) into the skeletal muscle of immunodeficient SCID mice, which were lacerated 4 weeks after transplantation. The MC13 cells regenerated numerous myofibers in the nonlacerated muscle and these myogenic cells were gradually replaced by myofibroblastic cells in the injured muscle. Our results suggest that the release of local environmental stimuli after muscle injury triggers the differentiation of myogenic cells (including MC13 cells) into fibrotic cells. These results demonstrate the potential of muscle-derived stem cells to differentiate into different lineages and illustrate the importance of controlling the local environment within the injured tissue to optimize tissue regeneration via the transplantation of stem cells.