应用痰抗酸杆菌涂片批量抽样对镜检中心进行评价

地点：进行痰抗酸菌镜检的指定镜检中心（DMC）和其他镜检中心（AMC），地区结核病中心（DTC）和参比实验室（RL）。 目的：使用盲法AFB痰涂片对不知晓AFB镜检质控的结核病实验室高级督导员（STLS）和经过培训知晓质控的参比实验室（RL）的技术员进行结果评估，确定批量抽样痰涂片的可行性。 方法：镜检中心（MC）的痰涂片送至地区结核病中心（DTC）和参比实验室；经过系统选择每个镜检中心每月送20个涂片；DMC的1547张涂片和AMC的726张涂片分别由DTC的STLS和RL的技术员进行检查，由第三者负责分析差别。 结果：和RL的1％相比，MC实验室技术员和DTC的STLSs之间的不符合率为4．7％。STLSs与RL实验室技术员各有70次和2次错误。 结论：AFB涂片的批量抽样在现场情况下是可行的。受过AFB涂片镜检质控培训的RL技术员对MC的评价比没有受过此训练的STLSS更有效。     

Current progress,challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease

Alzheimer''s disease (AD) is the most prevalent, progressive and multifaceted neurodegenerative disorder associated with cognition, memory and behavioural impairments. There is no approved diagnosis or cure for AD, and it affects both developed and developing countries and causes a significant social and economic burden. Extracellular senile plaques of amyloid beta (Aβ) and intracellular neurofibrillary tangles of phosphorylated Tau (pTau) in the brain are considered to be the pathophysiological hallmarks of AD. In an attempt to explain the complexity and multifactorial nature of AD, various hypotheses (Aβ aggregation, Tau aggregation, metal dyshomeostasis, oxidative stress, cholinergic dysfunction, inflammation and downregulation of autophagy) based on pathophysiological changes that occur during the onset and progression of AD have been proposed. However, none of the hypotheses is capable of independently explaining the pathological conditions observed in AD. The complex and multifaceted pathophysiological nature of AD has hampered the identification and validation of effective biomarkers for early diagnosis and the development of disease-modifying therapies. Nevertheless, the amyloid hypothesis is the most widely accepted and is closely correlated with disease symptoms of AD that encompass all the disease hypotheses. Therefore, amyloid plaques are ideal biomarkers for the development of an early diagnosis of AD. Similarly, the formation of amyloid plaques can also serve as a target for the design of therapeutic tools via an inclusive approach that considers multiple disease pathways involved in AD. Our review article briefly introduces pathophysiological factors involved in AD using interdependent but diverse hypotheses. Recent advances in the development of effective molecular tools and techniques for diagnostic and therapeutic interventions in AD, especially those in the advanced stages (clinical trials) of development, are given special consideration. In addition, contributions from our laboratory to the development of selective molecular tools for diagnostic and therapeutic interventions that target multifaceted toxicity in AD are also covered. In summary, we discuss diverse aspects of molecular mechanisms that underlie the pathogenesis of multifactorial AD, current progress and possible bottlenecks that have hampered the development of early diagnostic tools and effective drugs. Challenges and future prospects include the integration of various disease pathways for the successful development of an early diagnosis and effective drugs for the treatment of AD.

The diverse pathological mechanisms and their implications for the development of effective diagnostic and therapeutic interventions in Alzheimer''s disease are presented with current progress, challenges and future prospects.     

Multiple-echo proton spectroscopic imaging using time domain parametric spectral analysis

A multiple-echo MR spectroscopic imaging (MRSI) method is presented that enables improved metabolite imaging in the presence of local field inhomogeneities and measurement of transverse relaxation parameters. Short echo spacing is used to maximize signal energy from inhomogeneously line-broadened resonances, and time domain parametric spectral analysis of the entire echo train is used to obtain sufficient spectral resolution from the shortened sampling periods. Optimal sequence parameters for ¹H MRSI are determined by computer simulation, and performance is compared with conventional single-echo acquisition using phantom studies at a field strength of 4.7 T. A preliminary example for use at 1.5 T is also presented using phantom and human brain MRSI studies. This technique is shown to offer improved performance relative to single-echo MRSI for imaging of metabolites with shortened T₂* values due to the presence of local field inhomogeneities. Additional advantages are the intrinsic measurement of metabolite T₂ values and determination of metabolite integrals without T₂ weighting, thereby facilitating quantitative metabolite imaging.     

Volumetric proton spectroscopic imaging of mild traumatic brain injury

BACKGROUND AND PURPOSE: Poor clinical outcomes without notable neuroimaging findings after mild traumatic brain injury (MTBI) suggest diffuse tissue damage and altered metabolism not observable with conventional MR imaging and CT. In this study, MTBI-associated metabolic changes were assessed over the entire brain by using volumetric proton MR spectroscopic imaging (MRSI) and the findings related to injury and outcome assessments. METHODS: Fourteen subjects with mild closed head injury (Glasgow Coma Scale [GCS] scores of 13-15) underwent structural MR imaging and proton MRSI at 1.5 T within 1 month of injury. Distributions of N-acetylaspartate (NAA), total creatine (Cr), and total choline (Cho) were mapped over a wide region of the brain, and metabolite ratios were calculated for 25 regions without MR imaging abnormalities. Results were compared with data from 13 control subjects. RESULTS: Significant changes (P <.05) were found for some, but not all, brain regions for the average values from all MTBI subjects, with reduced NAA/Cr, increased Cho/Cr, and reduced NAA/Cho. Global NAA/Cho obtained from the sum of all sampled regions in two subjects was significantly reduced. Metabolite ratios were not significantly correlated with GCS score at admission or Glasgow Outcome Scale (GOS) score at 6 months after injury, although they were weakly correlated with GOS score at discharge. CONCLUSION: These results show evidence of widespread metabolic changes following MTBI in regions that appear normal on diagnostic MR images. Although the association with injury assessment and outcome is weak, this preliminary study demonstrates the applicability of volumetric proton MRSI for evaluating diffuse injury associated with MTBI.     

Hoffmann's syndrome with unusually long duration: Report on clinical,laboratory and muscle imaging findings in two cases

Two adult men presented with the rare Hoffmann''s syndrome (HS). Case 1: A 35-year-old male patient had progressive stiffness of lower limbs of 13 years and generalized muscle hypertrophy and myalgia of 3 years duration. Had periorbital edema, dry skin, generalized muscle hypertrophy and spastic dysarthria with hoarseness. Muscle power was normal. Jaw jerk and deep tendon reflexes were exaggerated. Case 2: A 24-year-old male patient presented with muscle hypertrophy from childhood, slowness in motor activities and hearing impairment. For 6 months, he had severe muscle pains, cramps and further increase in hypertrophy. He had yellow tinged, dry skin, hoarseness of voice, gross muscle hypertrophy and minimal weakness. Both had markedly elevated serum creatine kinase (CK) levels and high thyroid stimulating hormone, low free triiodothyronine and free thyroxine levels. Levothyroxine treatment demonstrated remarkable reduction in muscle bulk at 2 months in both and no symptoms at 6 months. Magnetic resonance imaging of lower limbs in both cases revealed almost identical features with involvement of the muscles of posterior and adductor compartment of thighs and posterior and lateral compartments of the legs. Differential diagnosis of long duration muscle pseudohypertrophy and elevated CK levels should include HS.     

Capillary electrophoresis analysis of nitrite and nitrate in sub-microliter quantities of airway surface liquid.

We developed a simple capillary electrophoresis (CE) method to measure nitrite and nitrate concentrations in submicroliter samples of rat airway surface liquid (ASL), a thin (10-30 microm) layer of liquid covering the epithelial cells lining the airways of the lung. The composition of ASL has been poorly defined, in large part because of the small sample volume (approximately 1-3 microl per cm2 of epithelium) and difficulty of harvesting ASL. We have used capillary tubes for ASL sample collection, with microanalysis by CE using a 50 mM phosphate buffer (pH 3), with 0.5 mM spermine as a dynamic flow modifier, and direct UV detection at 214 nm. The limit of detections (LODs), under conditions used, for ASL analysis were 10 microM for nitrate and 30 microM for nitrite (SIN= 3). Nitrate and nitrite were also measured in rat plasma. The concentration of nitrate was 102+/-12 microM in rat ASL and 70+/-1.0 microM in rat plasma, whereas nitrite was 83+/-28 microM in rat ASL and below the LOD in rat plasma. After instilling lipopolysaccharide intratracheally to induce increased NO production, the nitrate concentration in ASL increased to 387+/-16 microM, and to 377+/-88 microM in plasma. The concentration of nitrite increased to 103+/-7.0 microM for ASL and 138+/-17 microM for plasma.     

Hearing loss after noise exposure

The higher field strength magnetic resonance imaging (MRI) such as 3 Tesla (T) and above generates noise that has potential detrimental effects on the hearing. Temporary threshold shifts following MRI examination have been reported for MRI with lower field strength. Such effect, however, have not been reported so far for a 3 T MRI. We report a case that exemplifies the possible detrimental effects of a 3 T MRI generated noise on the auditory system. Our patient underwent investigation of his chronic backache in a 3 T MRI unit and developed hearing loss and tinnitus post-MRI examination. Hearing assessment was done using pure tone audiogram, distortion product otoacoustic emission (DPOAE) and brainstem electrical response audiometry (BERA) which revealed a unilateral sensorineural hearing loss which recovered within 3 days. However the tinnitus persisted. This is possibly a case of temporary threshold shift following noise exposure. However a sudden sensorineural hearing loss remains the other possibility.