Translocation between chromosome 5q35 and chromosome 11q13 – an unusual cytogenetic finding in a primary refractory acute myeloid leukemia

Cytogenetic abnormalities are observed in approximately two‐thirds of patients with acute myeloid leukemia (AML). Chromosome rearrangements are associated with specific subtypes of AML and associated prognosis. We report a patient with AML, M2, who was primarily refractory to standard induction chemotherapy with idarubicin and cytarabine. Flow cytometry of a bone marrow aspirate showed aberrant expression of B‐cell markers including CD19. Cytogenetic studies disclosed a translocation between 5q35 and 11q13. Fluorescence in situ hybridization analyses demonstrated that neither the NSD1 nor MLL genes were involved in this case. Further study is required to define conclusively the genes involved and their contribution to pathogenesis in this case.     

Alternating repetition time balanced steady state free precession.

A novel balanced SSFP technique for the separation or suppression of different resonance frequencies (e.g., fat suppression) is presented. The method is based on applying two alternating and different repetition times, TR(1) and TR(2). This RF scheme manipulates the sensitivity of balanced SSFP to off-resonance effects by a modification of the frequency response profile. Starting from a general approach, an optimally broadened stopband within the frequency response function is designed. This is achieved with a TR(2) being one third of TR(1) and an RF-pulse phase increment of 90 degrees . With this approach TR(2) is too short ( approximately 1 ms) to switch imaging gradients and is only used to change the frequency sensitivity. Without a significant change of the spectral position of the stopband, TR(1) can be varied over a range of values ( approximately 2.5-4.5 ms) while TR(2) and phase cycling is kept constant. On-resonance spins show a magnetization behavior similar to balanced SSFP, but with maximal magnetization at flip angles about 10 degrees lower than in balanced SSFP. The total scan time is increased by about 30% compared to conventional balanced SSFP. The new technique was applied on phantoms and volunteers to produce rapid, fat suppressed images.     

Chromosomal Rearrangements in Three Infertile Men

Summary:  Three chromosomal rearrangements: a balanced reciprocal translocation, t(14;10) (q22;q13), a Y-autosome translocation, t(Y;16) (q11;p13) and a deleted Y chromosome, Yq- were detected among 100 infertile men. The autosomal translocation, associated with oligozoospermia was found to be familial with various effects on the female carriers and the proband's father. The patients with the chromosome Y abberations were found to be azoospermic and might have lost the genes necessary for normal sperma-togenesis.
Zusammenfassung:  Unter 100 infertilen Männern wurden drei Chromosomenneuan-ordnungen entdeckt: eine balancierte reziproke Translokation, t(14;10) (q22;q13), eine Y-autosome Translokation, t(Y;16) (q11;p13) und eine Deletion des Y-Chromosoms, Yq-. Die autosomale Translokation bei Oligozoospermie zeigte sich familiär mit verschiedenen Auswirkungen bei den weiblichen Überträgern und dem Vater des Probanden. Die Patien-ten mit chromosomalen Y-Aberrational wiesen eine Azoospermie auf und scheinen die zur normalen Spermatogenese notwendigen Gene verloren zu haben.     

Role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation and the effect of bifidobacterial supplement on gut barrier function following burns

Early multiple organ dysfunction syndrome appears to be facilitated with bacterial translocation in severely burn injury, yet the mechanisms of bacterial translocation remains in dispute. The aim of this study was to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation following burns and the effects of bifidobacterial supplement on gut barrier. Methods: Wistar rats were randomly divided into burn group (Burn, n=60),sham burn group (SB, n=10) in experiment Ⅰ , and burn + saline group (BS, n=30), burn + bifidobacteria group (BB, n=30), and sham-burn + saline group (SS, n= 10) in experiment Ⅱ. Animals in BB group were fed bifidobacterial preparation (5 × 109 CFU/ml) after burns, 1.5ml,twice daily. Animals in BS and SS were fed saline. Samples were taken on days 1, 3, and 5 in burn groups, and on day 3 in sham-burn groups. The incidence of bacteria/endotoxin translocation and counts of Bifidobacterium, Fungi and Escherichia coli in gut mucosa were determined with standard methods. The levels of sIgA in mucus of small intestine were measured by RIA. The positive sIgA expression in lamina propria and ileum mucosal injury was evaluated light microscopically by blinded examiners. Results: Our results showed that the incidence of bacterial translocation was increased after burns, which was accompanied by significant decrease in number of bifidobacteria but significant increase in E. coli and fungi in gut mucosa, and elevation of levels of plasma endotoxin and IL-6 (P<0. 001).The incidence of bacterial translocation was markedly reduced after 3- and 5-day supplementation of bifidobacteria compared with control group (P<0.05). The counts of mucosal bifidobacteria were increased by 4- to 40-fold,while E. coli and fungi were decreased by 2- to 30-fold and 10- to 150-fold, respectively, after bifidobacterial supplementation in contrast to control group. The damage of mucosa tended to be less pronounced after 3-day bifidobacteria-supplemented formula compared with control group [grade 2(0-6) vs. grade 4(3-6), P<0.05]. Moreover, the expression and release of sIgA was markedly augmented after 3-day bifidobacteria-supplementation formula and it returned to normal range on day 5. Conclusion: The decrease in counts and proportion of bifidobacteria in mucous membrane flora may play an important role in the development of bacteria/endotoxin translocation following thermal injury. The supplement of exogenous bifidobacteria could per se improve gut barriers, and attenuate bacteria/endotoxin translocation secondary to major burns.     

Effects of granulocyte colony-stimulating factor on bacterial translocation due to burn wound sepsis

The presence of certain defects in both cellular and humoral immunity after thermal injury has been established. Likewise, the translocation of enteric bacteria to the mesenteric lymph nodes and to distant organs has also been observed following serious thermal injury. The effects of granulocyte colony-stimulating factor (G-CSF) on bacterial translocation, the small bowel mucosa, and cecal bacterial content were investigated in a rat model of burn wound sepsis in which albino Wistar rats were scalded over 30% of their bodies, after which the lesions were infected by 1×10⁸ colony-forming units (cfu)Pseudomonas aeruginosa. The control group was treated with 5% dextrose solution subcutaneously starting 2 days preburn, while the treatment group received 100μg/kg human G-CSF subcutaneously. On the 4th day post burn all animals were killed to examine the bowel and culture of the mesenteric lymph nodes (MLN), livers, and spleens. No significant differences were observed between the groups regarding the cecal bacterial content and small bowel; however, a difference was seen in the ratio of translocation in the MLN liver and spleen and quantitative MLN cultures. Based on these findings, G-CSF was thus found to be significantly effective in reducing bacterial translocation due to burn wound sepsis.     

Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis

The objective of this study is to investigate the effects of an acute necrotizing pancreatitis (ANP), without biliary obstruction, on the migrating motor complex (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and infection of the pancreas simultaneously. Rats were divided into four groups: mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs were harvested for microbial culturing 72 h after induction of pancreatitis. The splenic portion of the pancreas was taken for histology. During ANP the MMC cycle length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P < 0.05). The duodenum of ANP rats was in contrast with the other groups characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P < 0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram-negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A positive correlation (r = 0.85, P < 0.01) was found between the severity of pancreatitis and duodenal bacterial overgrowth. During ANP without biliary obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The correlation between the severity of pancreatitis, the disturbance of the MMC and SBBO suggests an important pathophysiological role of the proximal small bowel in the infection of pancreatic necrosis.     

The Effect of Cuts in Medicare Reimbursement on Hospital Mortality

Objective. To determine if patients treated at hospitals under different levels of financial strain from the Balanced Budget Act (BBA) of 1997 had differential changes in 30-day mortality, and whether vulnerable patient populations such as the uninsured were disproportionately affected.
Data Source. Hospital discharge data from all general acute care hospitals in Pennsylvania from 1997 to 2001.
Study Design. A multivariate regression analysis was performed retrospectively on 30-day mortality rates, using hospital discharge data, hospital financial data, and death certificate information from Pennsylvania.
Data Collection. We used 370,017 hospital episodes with one of four conditions identified by the Agency for Healthcare Research and Quality as inpatient quality indicators were extracted.
Principal Findings. The average magnitude of Medicare payment reduction on overall net revenues was estimated at 1.8 percent for hospitals with low BBA impact and 3.6 percent for hospitals with a high impact in 1998, worsening to 2 and 4.8 percent, respectively, by 2001. Operating margins decreased significantly over the time period for all hospitals ( p <.05). While unadjusted mortality rates demonstrated a disproportionate rise in mortality for patients from high impact hospitals from 1997 to 2000, adjusted analyses show no consistent, significant difference in the rate of change in mortality between high-impact and low-impact hospitals ( p =.04–.94). Similarly, uninsured patients did not experience greater increases in mortality in high-impact hospitals relative to low-impact hospitals.
Conclusions. An analysis of hospitalizations in the Commonwealth of Pennsylvania did not find an adverse impact of increased financial strain from the BBA on patient mortality either among all patients or among the uninsured.     

表皮生长因子改善移植小肠黏膜屏障功能的实验研究

目的了解表皮生长因子(epidermalgrowthfactor,EGF)对移植小肠通透性及细菌易位的作用。方法以Wistar大鼠为供体,SD大鼠为受体行异位全小肠移植,并以环孢素A(CsA,6mg.kg-1.d-1,im)抑制排斥反应。表皮生长因子组(EGF组)用微量输液泵持续均匀输入EGF200μg.kg-1.d-1;对照组输入等量生理盐水。第7天以乳果糖及甘露醇行移植肠灌注并收集尿液行高效液相色谱仪分析乳果糖及甘露醇含量,第8天采集移植肠系膜淋巴结及门静脉血行细菌培养。结果对照组尿液中乳果糖含量[(0.093±0.008)vs(0.015±0.002),P=0.0001]及乳果糖/甘露醇比值[(0.132±0.021)vs(0.020±0.005),P=0.0001]明显高于基准,EGF组乳果糖含量[(0.043±0.008)vs(0.015±0.002),P=0.0054]及乳果糖/甘露醇比值[(0.060±0.017)vs(0.020±0.005),P=0.0029]也较基准增加,EGF组乳果糖含量[(0.043±0.008)vs(0.093±0.008),P=0.0067)及乳果糖/甘露醇比值[(0.060±0.017)vs(0.132±0.021),P=0.0116]显著低于对照组。EGF组移植肠系膜淋巴结细菌阳性率为10%,对照组阳性率为60%,明显高于EGF组(P=0.028)。EGF组与对照组门静脉血培养阳性率比较差异无统计学意义(P>0.05)。结论本研究提示EGF能够降低同种移植小肠的通透性及细菌易位率,改善肠黏膜屏障功能。     

猪门静脉回流阻断模型内毒素的移位

【目的】拟在猪的肠血管阻断模型中探讨门静脉回流阻断肠淤血可能造成的内毒素移位和肿瘤坏死因子释放。【方法】采用种群相近体质量22～25kg雌性小猪8只，无感染症状。分离门静脉和肝后下腔静脉分别阻断、然后开放各60min．观察血压、心率，阻断前和开放60min各取回肠末端小肠全层行光镜、电镜检查，测定门、颈静脉血内毒素及肿瘤坏死因子（TNF—α）含量。【结果】门静脉和肝后下腔静脉阻断后，肠淤血、水肿，并随时间延长而加重，光镜检查表明实验后肠粘膜和腺体明显损伤，电镜检查表明细胞超微结构轻微异常。阻断前后的血内毒素、TNF—α含量无显著性差异。【结论】①肠静脉回流阻断60min引起的肠道淤血可导致肠粘膜屏障损伤。②在60min内肠淤血性的损伤不会引起肠腔内内毒素的大量移位及TNF—α的释放。