Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants

The germinal matrix (GM) located in the thick subependymal cell layer of the thalamostriate groove is a major site of cerebral hemorrhage in premature infants. Comparing the morphology of vasculature among GM, gray and white matter of the brain may help in understanding the pathogenesis of GM hemorrhage and also of periventricular leukomalacia. The objective of the present study was to determine the morphology of blood vessels in the GM, gray matter, and white matter and to examine maturational changes in the morphology of these vessels as a function of gestational age. We measured vessel density, percentage of blood vessel area, mean surface area, length, breadth, perimeter, radius, and shape of blood vessels in coronal sections of the GM, gray matter, and white matter in postmortem human brain samples for 17 fetuses and premature infants of gestational age 16-40 wk and 2 adults. We performed immunohistochemical staining using anti-laminin primary antibody, confocal microscopy to acquire images, and analysis using Metamorph version 6.1. Vessel density and the percentage of blood vessel area increased as a function of gestational age in the GM, gray matter, and white matter (p < 0.001 each). The blood vessel density and the percentage of blood vessel area were largest in the GM followed by gray matter and then white matter in all of the gestational age categories (p < 0.001 for all comparisons). Increased vascularity of the GM compared with gray and white matter may play a role in GM hemorrhage, whereas a relatively low vascularity of white matter may increase the propensity for the occurrence of periventricular leukomalacia in premature infants     

Magnetic resonance imaging of normal and pathological white matter maturation

Fifty children between 3 months postnatal and 16 years of age were examined by means of a 1.5 T superconductive magnet, run at 0.35 and 1.0 T. The myelination was studied qualitatively and quantitatively (relaxation times, proton densities, image contrast). With increasing age, a decrease of T1 and proton density of white matter was found, which was complete at one year of age. In regions with a slow progression of myelination, gray/white matter contrast showed an increase up to the end of the first decade. Pathological white matter maturation was diagnosed either as an abnormal transformation of myelin (characterized by abnormal relaxation values), or as a deficient or delayed myelin formation (in comparison with age-matched controls).     

新生鼠缺氧缺血脑损伤的组织学和MR影像变化

目的调查新生大鼠缺氧缺血脑白质和灰质损伤的组织学和磁共振（MR）影像的变化。方法7日龄Wistar鼠（n=24）随机分为假手术组和实验组（右颈动脉结扎＋吸入8％氧1．5h）。在缺氧前、缺氧最后5-10分钟、缺氧后1h和24h行头部MR扫描获得吧和表面弥散系数（ADC）。结果1．5h缺氧将结束时，在缺氧缺血半球皮质下白质和顶部灰质可见ADC明显降低和他增高；缺氧缺血后1h，皮质下白质和顶部灰质ADC部分恢复，他持续增高，而缺氧缺血后24h，T2进一步增高。与灰白质类似的MRI改变相反，组织学检查显示：缺血半球白质不可逆细胞损伤发生早于灰质。在缺氧缺血后1h，缺血半球皮质下白质可见神经纤维稀疏或紊乱，并可见TUNEL阳性细胞增加，而在缺血半球顶部灰质区未见明显细胞损伤或TUNEL阳性细胞增加，到缺氧缺血后24h，灰白质均可见明显的损伤。结论在目前的新生鼠脑缺氧缺血模型，吧和ADC均能发现急性缺氧缺血脑白质和灰质水肿或损伤，但它们不能区分白质和灰质不同的病理变化，组织学上新生鼠脑白质比灰质更易遭受缺氧缺血损害。     

Mucopolysaccharidosis: thickening of dura mater at the craniocervical junction and other CT/MRI findings

Cranial CT and/or MRI imaging of 8 patients with mucopolysaccharidosis (MPS) was retrospectively evaluated. Two patients had MPS IH, 1 had MPS IS, 1 had MPS IVA and 4 had MPS IV. CT and MRI showed thickening of dura mater at the cranio-cervical junction, causing narrowing of the subarachnoid space, in all the patients examined. Spinal cord compression was detected in 4 patients. Other findings were: white matter alterations, mild to severe hydrocephalus, skull dysplasia and odontoid dysplasia. White matter alterations were evident as large areas and as multiple dispersed spots of prolonged T1 and T2 value. Reduced gray/white matter contrast was demonstrated on T2-weighted MRI images. It is important to examine the cranio-cervical junction carefully for thickening of dura mater in all patients with mucopolysaccharidosis examined by CT or MRI, because of the generally progressive clinical course of MPS. In patients with symptomatic cord compression, surgical intervention should be considered.     

新生儿缺氧缺血性脑病磁共振动脉自旋标记成像33例报告

目的 探讨动脉自旋标记(arterial spin labeling,ASL) MR灌注技术在新生儿缺氧缺血性脑病(HIE)诊断中的应用价值.方法 选用7例无窒息病史以及无其他神经系统疾病的足月新生儿作为正常对照组,将33例有窒息缺氧病史,临床诊断为HIE的足月新生儿按照临床诊断标准分为轻度组(19例)、中度组(6例)和重度组(8例).正常对照组及HIE病例组均行常规横断位MRI(T1FLAIR、T2WI、T2FLAIR)、1 HMRS及ASL(FAIR序列)扫描.经ADW 4.3工作站Functool软件处理后,观察ASL灌注图像,并对病例组和正常对照组的感兴趣区(双侧灰质、白质、基底节区)进行信号强度值定量测量,求其平均值并进行组间比较.结果 正常对照组及病例组均获得了良好的ASL灌注图像.正常对照组灰质、白质及基底节区平均信号强度分别为125.34±11.76、73.42±11.67和173.65±15.49,差异有统计学意义(P＜0.05).HIE病例组灰质、白质及基底节区平均信号强度值为153.47±11.72、71.35±10.37和217.13±12.51,灰质及基底节区平均信号强度值与正常对照组差异具有统计学意义(P＜0.05),病例组白质平均信号强度值与对照组(两组信号强度值分别为73.42±11.67和71.35±10.37)差异无统计学意义(P＞0.05).结论 ASL灌注技术能够有效地检测HIE患者脑组织异常灌注情况,有助于判断患者脑损伤的程度,并为临床诊疗提供有力依据.     

表观弥散系数在2~12岁常规颅脑MRI正常的智力障碍/全面发育迟缓患儿中的应用

目的探讨快速自旋回波弥散加权成像（TSE-DWI）表观弥散系数（ADC）在2~12岁常规颅脑MRI正常的智力障碍/全面发育迟缓（ID/GDD）患儿中的应用价值。方法选择符合ID/GDD诊断标准且常规颅脑MRI正常的578例患儿及同年龄段375例正常儿童志愿者为研究对象,并收集其影像学和临床资料。所有研究对象均行颅脑TSE-DWI序列及常规序列扫描。分析正常对照组儿童各脑区不同年龄亚组、各年龄亚组不同ID/GDD程度患儿各脑区ADC值差异,社会适应行为评分（ABAS-Ⅱ）对ID/GDD患儿各脑区ADC值的影响。结果正常对照组额颞叶白质、胼胝体、内囊、半卵圆中心、小脑齿状核、视放射、丘脑、豆状核及尾状核ADC值随年龄升高而降低（P < 0.05）。各年龄组ID/GDD患儿深、浅部白质,深部灰质核团及浅部灰质4岁~组ADC值随ID/GDD程度升高而升高（P < 0.05）。深、浅部白质及深部灰质核团,各ID/GDD组ADC值随年龄的升高而降低（P < 0.05）。ID/GDD患儿ADC值随ABAS-Ⅱ评分升高而降低（P < 0.05）。结论 ADC能反映常规颅脑MRI正常ID/GDD患儿各脑区细微结构变化,对社会适应性方面也有一定的提示作用,可为ID/GDD患儿定量诊断提供客观依据。     

Effects of DTNBP1 genotype on brain development in children

Background: Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin‐binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain development is poorly understood. The present investigation examined for the first time the effects of DTNBP1 on brain structure in children. Our hypothesis was that a genetic variation in DTNBP1 (i.e., the single nucleotide polymorphism rs2619538) would be associated with differences in both gray and white matter brain regions previously implicated in schizophrenia. Methods: Magnetic resonance imaging and voxel‐based morphometry were used to examine brain structure in 52 male children aged between 10 and 12 years. Statistical inferences on the effects of DTNBP1 genotype on gray and white matter volume (GMV and WMV) were made at p < .05 after family‐wise error correction for multiple comparisons across the whole brain. Results: Individuals homozygous for the schizophrenia high‐risk allele (AA) compared with those homozygous for the low‐risk allele (TT) expressed reduced GMV in the left anterior cingulate gyrus and reduced WMV in the left medial frontal area. Conclusions: Our results suggest that genetic variation in DTNBP1 is associated with differences in gray and white matter; and that these effects are already evident in children as young as 10–12 years. These findings are consistent with the notion that the DTNBP1 genotype influences brain development and may thereby modulate vulnerability to schizophrenia.     

Brain abnormalities in Williams syndrome: A review of structural and functional magnetic resonance imaging findings

Williams syndrome (WS) is rare genetic form of mental retardation caused by a microdeletion on chromosome 7q11.23 that causes cognitive impairment and a variety of physical abnormalities. MRI studies of WS have demonstrated a series of brain abnormalities, including decreased brain size, with a relatively greater decrease in the volume of the cerebral white matter volume as compared to the cerebral gray matter. Moreover there is evidence that the posterior cerebrum is more affected in that persons with WS have a greater ratio of frontal to posterior regional volume. These findings are further supported by automated analyses that have shown reduced gray matter density in the superior parietal lobe areas. Functional MRI studies have demonstrated hypofunction immediately adjacent to, and anterior to, the intraparietal sulcus, a region in which structural brain differences had been identified. These anatomical and functional differences are consistent with the neuropsychological profile of WS – in particular, with evidence of dorsal stream visual processing deficits. To date, however, studies have always been performed in comparison to intellectually average controls. It is not clear, therefore, if findings are specific to the WS population or whether they represent a morphological disturbance characteristic of mental retardation, irrespective of genetic etiology. In this article, we reviewed recent advances underlying the structural and functional neural substrate of WS in Medical Literature Analysis and Retrieval System Online (MEDLINE; 1997–2007).     

Early reduction of total N-acetyl-aspartate-compounds in patients with classical vanishing white matter disease. A long-term follow-up MRS study

The neuropathology of vanishing white matter (VWM) disease is characterized by a loss of white matter (WM). Although recent histopathological studies suggest a primary glial dysfunction, the purpose of this work was to assess the extent of axonal involvement in VWM using long-term follow-up proton MR spectroscopy. White and gray matter of nine children with genetically proven VWM and late infancy/early childhood onset were investigated with short-echo time, single-voxel proton MR spectroscopy over up to 8 years starting as early as less than 2 years after the onset of symptoms (5 patients). Total N-acetyl-aspartate (-51% from normal control), creatine and phosphocreatine (-47%), and myo-inositol (-49%) were reduced in WM at early disease stages. Choline-containing compounds were less severely decreased (-31%). Follow-up investigations revealed progressive reduction of all metabolites in WM. In gray matter, no distinct changes were detected at early stages. Later total N-acetyl-aspartate decreased slightly (-22%). Assuming the metabolite alterations to primarily reflect changes in cellular composition, the observed pattern indicates early axonal involvement or loss as well as relatively enhanced turnover of myelin. These early stages are followed by a complete cellular loss in cerebral WM.     

Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study

OBJECTIVES: The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. METHODS: From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Women's Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. RESULTS: The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse white matter atrophy, ventriculomegaly, immature gyral development, and enlarged subarachnoid space was found in 10 of 11 infants with birth gestation <26 weeks. Given the later outcome of these infants, this pattern may have very high risk for later global neurodevelopmental disability. CONCLUSIONS: This MRI study confirms a high incidence of cerebral white matter abnormality at term in an unselected population of premature infants, which is predominantly a result of noncystic injury in the extremely immature infant. We confirm that the major perinatal risk factors for white matter abnormality are related to perinatal infection, particularly maternal fever and infant sepsis, and hypotension with inotrope use. We have defined a distinct pattern of diffuse white and gray matter abnormality in the extremely immature infant.     

Neuroimaging abnormalities in Griscelli's disease

Griscelli's disease is a rare autosomal recessive immunodeficiency syndrome. We report a 7-1/2-month-old white girl who presented with this syndrome, but initially without neurological abnormalities. Initial CT of the brain was normal. Despite haematological remission with chemotherapy, she developed neurological symptoms, progressing to coma. At this time, CT showed areas of coarse calcification in the globi pallidi, left parietal white matter and left brachium pontis. Hypodense areas were present in the genu and posterior limb of the internal capsule on the right side, as well as posterior aspects of both thalami, together with minimal generalised atrophy. MRI revealed areas of increased T2 signal and a focal area of abnormal enhancement in the subcortical white matter. Griscelli's disease should be added to the list of acquired neuroimaging abnormalities in infants.     

磁共振成像表观扩散系数变化对新生儿化脓性脑膜炎脑损伤纵向评估

背景：既往尚无新生儿化脓性脑膜炎在不同颅脑并发症下ADC值的纵向变化研究。 目的：回顾性总结新生儿化脓性脑膜炎在发病后不同病程阶段的头颅MR表现,在髓鞘化过程中分析不同颅脑并发症下脑组织ADC值随病程的变化规律。 设计：病例对照研究。 方法：以足月新生儿化脓性脑膜炎并行头颅MR检查者为病例组,基于颅脑并发症中有无脑实质损伤灶和脑积水分为病例1组（无脑实质损伤灶和脑积水）、病例2组（有脑实质损伤灶,无脑积水）、病例3组（有脑积水无脑实质损伤灶）和病例4组（有脑实质损伤灶和脑积水）。以发病至头颅MR检查间隔时间0~7 d、~28 d、~60 d和~120 d分为病程A~D组;根据MR检查时患儿日龄,病程A组分为A1组（0~14 d）和A2组（~28 d）,病程B组分为B1组（~28 d）和B2组（~60 d）。与病例组同期因其他疾病在同院行常规头颅MR且未观察到异常病变的儿童为对照组。 主要结局指标：相同日龄或相同病程下MR评估新生儿化脓性脑膜炎脑实质ADC值变化趋势。 结果：173例新生儿化脓性脑膜炎进入本文分析,病例组MR检查302例次,病程A~D组有241例次MR检查的ADC值进入本文分析;对照组20例。随着日龄的增加,对照组和病例组ADC值均呈降低趋势。不同病程(相同日龄)比较结果中,大脑皮层、深部白质在各个病程中,病例1~3组和对照组ADC值差异均无统计学意义（胼胝体压部的部分病程除外）;皮层下白质在病程0~60 d中,病例2和3组ADC值明显低于对照组,病例3组及部分病程中病例2组ADC值明显低于病例1组,皮层下白质在病程61~120 d中,病例2、3组和对照组ADC值差异无统计学意义,病例1组(除外顶叶白质)ADC值明显高于对照组;深部灰质核团在病程0~30 d中,病例1~3组ADC值明显低于对照组,在病程31~120 d中,病例1~3组和对照组ADC值差异均无统计学意义。 结论：在新生儿化脓性脑膜炎患儿,皮层下白质在病程1~2个月ADC值降低,病程3~4个月时ADC值正常或升高,提示髓鞘化进程受阻;深部灰质核团ADC值在病程1个月内降低,而病程2~4个月时恢复正常。MR DWI定量ADC值有助于对无脑结构损伤的新生儿脑膜炎微观损伤的评估。     

超早产儿脑病危险因素的病例对照研究

目的：了解超早产儿（胎龄＜28周）脑病的发生状况并探讨其发生的危险因素。方法：收集复旦大学附属儿科医院NICU 2009年1月1日至2015年12月31日期间住院的、出生胎龄＜28周的、于纠正胎龄足月时或出院前完成MRI检查的超早产儿,排除纠正胎龄或出院时MRI单纯脑出血的病例。根据头颅MRI影像学报告结果分为单纯EOP组、EOP+出血组和正常组,采集与发生EOP可能相关的母亲和新生儿影响因素,三组之间进行单因素比较。结果：115例超早产儿进入本文分析,单纯EOP 组20例,EOP+出血组15例,正常组80例。35例EOP患儿中,白质损伤31例（88.6%）,灰质损伤4例（11.4%）,小脑损伤3例（8.6%）,多发广泛损伤1例（2.9%）,白质合并小脑损伤2例（5.7%）。脑白质损伤中,脑室周围白质损伤17例,其中非囊性损伤16例,囊性PVL1例;皮层下白质损伤14例,其中额叶损伤7例。单因素分析显示,单纯EOP组、EOP+出血组、正常组3组比较,母亲因素和新生儿因素差异均无统计学意义（P均＞0.05）。结论：超早产儿EOP与早产儿脑病一样最多见于脑白质损伤,影响超早产儿脑病为非单一危险因素起作用。     

Proton magnetic resonance spectroscopy: normal findings in the cerebellar hemisphere in childhood

BACKGROUND: The cerebellar hemispheres (CER) are different from the supratentorial white and gray matter embryologically, in cytoarchitecture, and probably in metabolic activity. Proton magnetic resonance spectroscopy ((1)H MRS) can provide a noninvasive biochemical analysis of this region. OBJECTIVE: To study, with (1)H MRS, metabolite concentrations in CER as a function of age and compare these metabolic data with those of parietoccipital white matter (PO WM) in healthy children. MATERIALS AND METHODS: Using single-voxel (1)H MRS, we studied 37 volunteers (3-18 years) with normal MRI scans of the brain. (1)H MRS was performed using the PRESS technique in CER and PO WM. The NAA/Cr, Cho/Cr, NAA/H(2)O, Cr/H(2)O, and Cho/H(2)O ratios were analyzed as a function of age. Metabolic data from these regions were compared. RESULTS: The NAA/Cr ratio tended to increase with age in CER. Mean NAA/Cr and Cho/Cr ratios were found to be lower in CER than in PO WM. Mean NAA/H(2)O, Cr/H(2)O, and Cho/H(2)O ratios in CER were higher than in the PO WM. CONCLUSION: Our data confirm the regional variations between CER and PO WM metabolite ratios, and demonstrate a tendency of age-dependent change of the NAA/Cr ratio in CER. The creatine concentration was significantly higher in the cerebellum than in the PO WM.     

Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS.

Regional changes of metabolite concentrations during human brain development were assessed by quantitative localized proton magnetic resonance spectroscopy in vivo. Apart from measurements in young healthy adults, the study was based on regional spectra from 97 children who were either healthy or suffered from mental retardation, movement disorders, epilepsies, neoplasm, or vascular malformation. Metabolite quantitation focused on cortical gray and white matter, cerebellum, thalamus, and basal ganglia in six age groups from infancy to adulthood. During infancy and childhood, the concentration of the neuroaxonally located N-acetylasparate increased in gray matter, cerebellum, and thalamus, whereas a constant level was detected in white matter. These findings are in line with regional differences in the formation of synaptic connections during early development and suggest a role of N-acetylaspartate as a marker of functioning neuroaxonal tissue rather than of the mere presence of nerve cells. This view is further supported by high concentrations of taurine in gray matter and cerebellum during infancy, because taurine is also believed to be involved in the process of synapse formation. Remarkably, in basal ganglia both N-acetylaspartate and taurine remain constant at relatively high concentrations. Other metabolite changes during maturation include increases of N-acetylaspartylglutamate, especially in thalamus and white matter, and a decrease of glutamine in white matter. Despite regional differences and some small changes during the first year of life, the concentrations of creatine, phosphocreatine, choline-containing compounds, myoinositol, and glutamate remain constant afterward. The creatine to phosphocreatine concentration ratio yields 2:1 throughout the human brain irrespective of region or age. The observed increase of the proton resonance line-width with age is most pronounced in basal ganglia and corresponds to the age-related and tissue-dependent increase of brain iron.     

Neuroradiological Findings in Glutaric Aciduria Type I: Report of Four Japanese Patients

We examined neuroradiological computerized tomography (CT) findings and the clinical course of four Japanese children with glutaric aciduria type I (GA1) whose enzyme activity of glutaryl-CoA dehydrogenase was undetectable. Brain CT in all cases examined showed low density white matter, fluid collection in bilateral frontotemporal regions (particularly surrounding the Sylvian fissures), enlargement of the lateral ventricles and slight atrophy of the basal ganglia. Although these findings seemed to be characteristic for GA1, they were unlikely to be more extended, at least over 2 years after infancy. The low density white matter was observed more evidently in the neonatal or early infantile periods than in later periods. The degree of enlargement of fissures in bilateral frontotemporal regions about the Sylvian fissures appeared to correlate with the severity of symptoms such as dystonia or choreo-athetosis. Magnetic resonance images (MRI) in one case showed bilateral linear-shaped low intensity in areas of the external capsules and putamen on a Tl-weighted image. These CT and MRI findings, as well as clinical symptoms such as choreoathetosis or dystonia, may suggest that metabolic abnormalities in GA1, such as glutaconate, are toxic to the extrapyramidal tract system in the central nervous system, and that the clinical symptoms of the patients are attributable to atrophy of basal ganglia. Brain CT may be useful in diagnosis and evaluation of the clinical course of GA1 patients.     

Stem Cell Through Present and Future

Stem cell transplantation (SCT) has the potential to transform the lives of children with a wide variety of genetic diseases, ranging from inherent defects of hemopoietic cell production or function through to metabolic diseases mostly affecting solid organs. For these children life expectancy or quality of life would otherwise be very poor.1 It ranks as one of the most remarkable therapeutic advances of the past 40 years. Despite rapid technological improvements, however, there are still many short term risks and potential long term toxicities. Consequently, the rapid emergence of alternative therapies (including new drugs, enzyme and gene therapies), necessitate constant re-evaluation of the risk/benefit ratio for each disease and hence the appropriateness of SCT. This review describes the major aspects of the transplant process, indications for transplantation, outcome statistics, and areas where alternative therapies are becoming available. SCT remains a highly experimental therapy. Due to the relatively short history of the discipline no data exists on truly long term follow up. This is important as some organs benefit relatively poorly or problems may emerge which were never apparent as part of the untreated disease. The speed of technological change makes randomised trials on these diseases, which are individually quite rare, almost impossible to perform.     

Stem Cell Through Present and Future

Stem cell transplantation (SCT) has the potential to transform the lives of children with a wide variety of genetic diseases, ranging from inherent defects of hemopoietic cell production or function through to metabolic diseases mostly affecting solid organs. For these children life expectancy or quality of life would otherwise be very poor.1 It ranks as one of the most remarkable therapeutic advances of the past 40 years. Despite rapid technological improvements, however, there are still many short term risks and potential long term toxicities. Consequently, the rapid emergence of alternative therapies (including new drugs, enzyme and gene therapies), necessitate constant re-evaluation of the risk/benefit ratio for each disease and hence the appropriateness of SCT. This review describes the major aspects of the transplant process, indications for transplantation, outcome statistics, and areas where alternative therapies are becoming available. SCT remains a highly experimental therapy. Due to the relatively short history of the discipline no data exists on truly long term follow up. This is important as some organs benefit relatively poorly or problems may emerge which were never apparent as part of the untreated disease. The speed of technological change makes randomised trials on these diseases, which are individually quite rare, almost impossible to perform.     

多药耐药基因介导的骨髓保护在肝癌小鼠化疗时的富集效应

目的 探讨多药耐药基因转染小鼠骨髓单个核细胞移植后,化疗时其在体内的表达、分布以及在骨髓和外周血的富集效应.方法 骨髓造血细胞转染外源性多药耐药基因后移植入荷瘤Balb/c小鼠,免疫组化和RT-PCR观察mdr1基因在骨髓造血细胞、外周血单个核细胞及重要脏器的表达和分布;监测外周血白细胞变化及肿瘤组织P-糖蛋白表达.结果 外源性多药耐药基因在重要脏器和肿瘤组织无表达;化疗前骨髓细胞和外周血的P-糖蛋白表达阳性率分别为(9.36±1.84)%、(8.52±1.26)%,化疗药物剂量递增时,P-糖蛋白表达阳性率增高;移植未转染组与移植转染组外周血白细胞计数差异有统计学意义(P＜0.01).结论 外源性多药耐药基因转染在骨髓造血细胞和外周血单个核细胞有持续较高表达,在重要脏器无表达;随化疗药物剂量递增时骨髓和外周血有明显的富集效应;多药耐药基因转染介导保护骨髓在超剂量化疗中获得显著效果.