定量组织速度成像技术评价阿霉素诱导兔心肌病模型：与常规经胸超声心动图比较

目的:采用定量组织速度成像技术评价阿霉素诱导兔心肌病模型,并与常规经胸超声心动图比较其评估优势。方法:实验于2005-06/2006-08在大连医科大学完成。①实验分组及处理:取纯种新西兰白兔22只,雌雄不限,随机分成阿霉素组12只,给予阿霉素每次2mg/kg,以1g/L耳缘静脉注射,每周1次,注射8周;对照组10只每周注射2mL/kg生理盐水,共8周。②实验评估:每周应用HPSonos5500型彩色多普勒超声诊断仪(美国Agilent公司生产)对两组兔心脏进行左室收缩末期和舒张末期内径明、室间隔厚度、E峰、射血分数、左室短轴缩短率等常规超声参数测量,使用GEVivid7型彩色多普勒超声诊断仪(美国GE公司生产)进行收缩期和舒张期峰值速度、收缩期加速度定量组织速度成像参数测定。结果:22只兔进入统计。①对照组1～12周各参数与阿霉素组基础状态下比较无明显差异(P>0.05)。②第4周阿霉素组二尖瓣环运动的平均收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P均<0.05)。③第7周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),E峰较基础状态明显减低(P<0.05)。④第8周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),E峰较基础状态明显减低(P<0.01),左室收缩末期和舒张末期内径明显增大(P<0.05)。⑤第12周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),左室收缩末期和舒张末期内径明显增大(P<0.01),室间隔厚度、左室后壁厚度明显变薄(P<0.05),射血分数、左室短轴缩短率和E峰明显减低(P<0.01)。结论:定量组织速度成像参数可有效评价阿霉素诱导心肌病模型兔心肌的病理变化,较常规超声参数更敏感。     

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.     

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

Blood loss and contributing factors in femoral fracture surgery

Background

Substantial blood losses frequently accompany orthopedic procedures.

Methods

We prospectively noted peri-operative hemoglobin changes in 93 patients undergoing surgery for femoral fracture with an aim of establishing blood loss and related factors.

Results

The mean total blood loss assessed 72 hours after the surgical procedure was 3.31 (SD 1.56) units of whole blood. A multiple regression analysis revealed diathermy use and a simple fracture pattern as significant factors in reducing blood loss (p<0.01).

Conclusions

Open intramedullary fixation of femur fractures leads to considerable peri-operative blood loss. This is can be reduced by use of diathermy during surgery.     

Atlanto-axial rotatory fixation: Improved demonstration using spiral CT

Atlanto-axial rotatory fixation (AARF) is an uncommon condition which is often missed at presentation because of its rarity and the relative subtlety of plain film X-ray findings, but early detection and appropriate management are vital for a cure. We describe three cases in which the use of spiral computed tomography scanning with 3D and sagittal reconstructions greatly aided diagnosis and management. The 3D images gave a more graphic picture of the overall alignment of the upper cervical spine and the skull base, while the sagittal reconstructions demonstrated the presence or absence of compensatory atlanto-occipital subluxation. The literature is briefly reviewed.     

Estimating the prevalence of Ecstasy use among juvenile offenders

To date, no studies have examined Ecstasy use among criminal justice populations. Focusing on individuals under criminal justice supervision is useful because "new" illegal drugs will typically take root in a criminal population before diffusing to the general population. In the current study, self-report drug use data and urine specimens were collected from 209 juvenile offenders surveyed through Maryland's Offender Population Urinalysis Screening (OPUS) Program. Prevalence estimates are generated and associations between Ecstasy use, demographic characteristics, and alcohol and other drug use are explored. Sixteen percent of the sample reported using Ecstasy within the past 12 months, an estimate almost three times as high as grade school and high school students surveyed through the Monitoring the Future survey. Compared to nonusers. Ecstasy users were significantly more likely to be female (45% versus 20%, p < 0.01), White (82% versus 22%, p < 0.001), and out of school (39% versus 20%, p < 0.05). Associations were also found between Ecstasy use and the use of other drugs. These findings suggest that the recent use of Ecstasy among juvenile offenders is higher than estimated use in the general student population, and that youthful offenders may represent an important population for potential intervention.