Showing papers by "Erasmus University Rotterdam published in 2003"

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

Abstract: Background Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. Methods We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. Results After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 perce...

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

Abstract: In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Abstract: Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

Abstract: The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.

Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

Abstract: In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.

Silent brain infarcts and the risk of dementia and cognitive decline

Abstract: BACKGROUND Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.

Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group

Abstract: The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

Understanding the Effect of Customer Relationship Management Efforts on Customer Retention and Customer Share Development

Abstract: Scholars have questioned the effectiveness of several customer relationship management strategies. The author investigates the differential effects of customer relationship perceptions and relationship marketing instruments on customer retention and customer share development over time. Customer relationship perceptions are considered evaluations of relationship strength and a supplier’s offerings, and customer share development is the change in customer share between two periods. The results show that affective commitment and loyalty programs that provide economic incentives positively affect both customer retention and customer share development, whereas direct mailings influence customer share development. However, the effect of these variables is rather small. The results also indicate that firms can use the same strategies to affect both customer retention and customer share development.

Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program

Abstract: Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytc leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n = 278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.

The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial.

Abstract: BackgroundThe prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago, but are less clear in those with mildly to moderately elevated blood pressure.ObjectiveTo assess whether candesartan-based antihypertensive treatment in el

Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer.

Abstract: textBACKGROUND: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening. METHODS: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs. RESULTS: Mean lead times and rates of overdetection depended on a man's age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48% (range = 44%-55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%-87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected. CONCLUSIONS: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year.

The Impact of Entrepreneurship on Economic Growth

Abstract: The present chapter deals with the consequences of entrepreneurship for macro-economic growth. It consists of eight sections: (1) Introduction; (2) The influence of economic development on entrepreneurship; (3) Types of entrepreneurship and their relation to economic growth; (4) The effects of the choice between entrepreneurship and employment; (5) Entrepreneurship in endogenous growth models; (6) Strands of empirical evidence; (7) The time lag structure; and (8) Conclusion.

Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes

Abstract: Background—Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown. Methods and Results—MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (350 g/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 g/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P0.023), C-reactive protein (1.25; P0.044), vascular endothelial growth factor (HR 1.87; P0.041), soluble CD40 ligand (HR 2.78; P0.001), and MPO (HR 2.11; P0.008) were all independent predictors of the patient’s 6-month outcome. Conclusions—In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS. (Circulation. 2003;108:1440-1445.)

Catastrophe and impoverishment in paying for health care: with applications to Vietnam 1993–1998

Abstract: This paper presents and compares two threshold approaches to measuring the fairness of health care payments, one requiring that payments do not exceed a pre-specified proportion of pre-payment income, the other that they do not drive households into poverty. We develop indices for 'catastrophe' that capture the intensity of catastrophe as well as its incidence and also allow the analyst to capture the degree to which catastrophic payments occur disproportionately among poor households. Measures of poverty impact capturing both intensity and incidence are also developed. The arguments and methods are empirically illustrated with data on out-of-pocket payments from Vietnam in 1993 and 1998. This is not an uninteresting application given that 80% of health spending in that country was paid out-of-pocket in 1998. We find that the incidence and intensity of 'catastrophic' payments - both in terms of pre-payment income as well as ability to pay - were reduced between 1993 and 1998, and that both incidence and intensity of 'catastrophe' became less concentrated among the poor. We also find that the incidence and intensity of the poverty impact of out-of-pocket payments diminished over the period in question. Finally, we find that the poverty impact of out-of-pocket payments is primarily due to poor people becoming even poorer rather than the non-poor being made poor, and that it was not expenses associated with inpatient care that increased poverty but rather non-hospital expenditures.

Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using 'real-time' quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) - a Europe against cancer program

Abstract: Real-time quantitative RT-PCR (RQ-PCR) is a sensitive tool to monitor minimal residual disease (MRD) in leukemic patients through the amplification of a fusion gene (FG) transcript. In order to correct variations in RNA quality and quantity and to calculate the sensitivity of each measurement, a control gene (CG) transcript should be amplified in parallel to the FG transcript. To identify suitable CGs, a study group within the Europe Against Cancer (EAC) program initially focused on 14 potential CGs using a standardized RQ-PCR protocol. Based on the absence of pseudogenes and the level and stability of the CG expression, three genes were finally selected: Abelson (ABL), beta-2-microglobulin (B2M), and beta-glucuronidase (GUS). A multicenter prospective study on normal (n=126) and diagnostic leukemic (n=184) samples processed the same day has established reference values for the CG expression. A multicenter retrospective study on over 250 acute and chronic leukemia samples obtained at diagnosis and with an identified FG transcript confirmed that the three CGs had a stable expression in the different types of samples. However, only ABL gene transcript expression did not differ significantly between normal and leukemic samples at diagnosis. We therefore propose to use the ABL gene as CG for RQ-PCR-based diagnosis and MRD detection in leukemic patients. Overall, these data are not only eligible for quantification of fusion gene transcripts, but also for the quantification of aberrantly expressed genes.

Silent Brain Infarcts and White Matter Lesions Increase Stroke Risk in the General Population: The Rotterdam Scan Study

Abstract: Background and Purpose— Silent brain infarcts and white matter lesions are associated with an increased risk of subsequent stroke in minor stroke patients. In healthy elderly people, silent brain infarcts and white matter lesions are common, but little is known about their relevance. We examined the risk of stroke associated with these lesions in the general population. Methods— The Rotterdam Scan Study is a population-based prospective cohort study among 1077 elderly people. The presence of silent brain infarcts and white matter lesions was scored on cerebral MRI scans obtained from 1995 to 1996. Participants were followed for stroke for on average 4.2 years. We estimated the risk of stroke in relation to presence of brain lesions with Cox proportional hazards regression analysis. Results— Fifty-seven participants (6%) experienced a stroke during follow-up. Participants with silent brain infarcts had a 5 times higher stroke incidence than those without. The presence of silent brain infarcts increased the...

Networks in entrepreneurship: The case of high-technology firms

Abstract: The value of networks as an integral part of the explanation of entrepreneurial success is widely acknowledged. However, the network perspective does not specify the role of networks in the emergence and early growth of a venture. We have distinguished three entrepreneurial processes in new venture development, i.e. discovery of opportunities, securing resources, and obtaining legitimacy, which are of importance for survival and performance. This paper examines how these processes are influenced by strong and/or weak ties and whether the degree of innovation (incremental versus radical) acts as a contingency factor in the way network ties support entrepreneurial processes. In this explorative study three cases on high technology firms in The Netherlands provide empirical material enabling us to develop a number of propositions on the network effect, in particular the mix of strong and weak ties, on the three entrepreneurial processes.

Aetiology: Koch's postulates fulfilled for SARS virus.

Abstract: Severe acute respiratory syndrome (SARS) has recently emerged as a new human disease, resulting globally in 435 deaths from 6,234 probable cases (as of 3 May 2003). Here we provide proof from experimental infection of cynomolgus macaques (Macaca fascicularis) that the newly discovered SARS-associated coronavirus (SCV) is the aetiological agent of this disease. Our understanding of the aetiology of SARS will expedite the development of diagnostic tests, antiviral therapies and vaccines, and may allow a more concise case definition for this emerging disease.

Drug craving and addiction: integrating psychological and neuropsychopharmacological approaches

Abstract: In the present review, an integrated approach to craving and addiction is discussed, which is based on recent insights from psychology and neuropsychopharmacology. An integrated model explains craving and relapse in humans by the psychological mechanism of "attentional bias" and provides neuropsychopharmacological mechanisms for this bias. According to this model, cognitive processes mediate between drug stimulus and the subject's response to this stimulus and subsequent behavioral response (e.g., drug use, relapse). According to the model, a conditioned drug stimulus produces an increase in dopamine levels in the corticostriatal circuit, in particular the anterior cingulate gyrus, amygdala, and nucleus accumbens, which in turn serves to draw the subject's attention towards a perceived drug stimulus. This process results in motor preparation and a hyperattentive state towards drug-related stimuli that, ultimately, promotes further craving and relapse. Evidence for this attentional bias hypothesis is reviewed from both the psychopharmacological and the neuroanatomical viewpoints. The attentional bias hypothesis raises several suggestions for clinical approaches and further research.

Widening socioeconomic inequalities in mortality in six Western European countries

Abstract: OBJECTIVES: During the past decades a widening of the relative gap in death rates between upper and lower socioeconomic groups has been reported for several European countries. Although differential mortality decline for cardiovascular diseases has been suggested as an important contributory factor, it is not known what its quantitative contribution was, and to what extent other causes of death have contributed to the widening gap in total mortality. METHODS: We collected data on mortality by educational level and occupational class among men and women from national longitudinal studies in Finland, Sweden, Norway, Denmark, England/Wales, and Italy (Turin), and analysed age-standardized death rates in two recent time periods (1981-1985 and 1991-1995), both total mortality and by cause of death. For simplicity, we report on inequalities in mortality between two broad socioeconomic groups (high and low educational level, non-manual and manual occupations). RESULTS: Relative inequalities in total mortality have increased in all six countries, but absolute differences in total mortality were fairly stable, with the exception of Finland where an increase occurred. In most countries, mortality from cardiovascular diseases declined proportionally faster in the upper socioeconomic groups. The exception is Italy (Turin) where the reverse occurred. In all countries with the exception of Italy (Turin), changes in cardiovascular disease mortality contributed about half of the widening relative gap for total mortality. Other causes also made important contributions to the widening gap in total mortality. For these causes, widening inequalities were sometimes due to increasing mortality rates in the lower socioeconomic groups. We found rising rates of mortality from lung cancer, breast cancer, respiratory disease, gastrointestinal disease, and injuries among men and/or women in lower socioeconomic groups in several countries. CONCLUSIONS: Reducing socioeconomic inequalities in mortality in Western Europe critically depends upon speeding up mortality declines from cardiovascular diseases in lower socioeconomic groups, and countering mortality increases from several other causes of death in lower socioeconomic groups.

Incidence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study

Abstract: Background and Purpose— Silent brain infarcts are commonly seen on magnetic resonance imaging (MRI) both in patients with a first stroke and in healthy elderly persons. These infarcts seem associat...

Dialectical behaviour therapy for women with borderline personality disorder: 12-month, randomised clinical trial in The Netherlands.

Abstract: Background Dialectical behaviour therapy (DBT) is widely considered to be a promising treatment for borderline personality disorder (BPD). However, the evidence for its efficacy published thus far should be regarded as preliminary. Aims To compare the effectiveness of DBT with treatment as usual for patients with BPD and to examine the impact of baseline severity on effectiveness. Method Fifty-eight women with BPD were randomly assigned to either 12 months of DBT or usual treatment in a randomised controlled study. Participants were recruited through clinical referrals from both addiction treatment and psychiatric services. Outcome measures included treatment retention and the course of suicidal, self-mutilating and self-damaging impulsive behaviours. Results Dialectical behaviour therapy resulted in better retention rates and greater reductions of self-mutilating and self-damaging impulsive behaviours compared with usual treatment, especially among those with a history of frequent self-mutilation. Conclusions Dialectical behaviour therapy is superior to usual treatment in reducing high-risk behaviours in patients with BPD.

Visualization of Microtubule Growth in Cultured Neurons via the Use of EB3-GFP (End-Binding Protein 3-Green Fluorescent Protein)

Abstract: Several microtubule binding proteins, including CLIP-170 (cytoplasmic linker protein-170), CLIP-115, and EB1 (end-binding protein 1), have been shown to associate specifically with the ends of growing microtubules in non-neuronal cells, thereby regulating microtubule dynamics and the binding of microtubules to protein complexes, organelles, and membranes. When fused to GFP (green fluorescent protein), these proteins, which collectively are called +TIPs (plus end tracking proteins), also serve as powerful markers for visualizing microtubule growth events. Here we demonstrate that endogenous +TIPs are present at distal ends of microtubules in fixed neurons. Using EB3-GFP as a marker of microtubule growth in live cells, we subsequently analyze microtubule dynamics in neurons. Our results indicate that microtubules grow slower in neurons than in glia and COS-1 cells. The average speed and length of EB3-GFP movements are comparable in cell bodies, dendrites, axons, and growth cones. In the proximal region of differentiated dendrites approximately 65% of EB3-GFP movements are directed toward the distal end, whereas 35% are directed toward the cell body. In more distal dendritic regions and in axons most EB3-GFP dots move toward the growth cone. This difference in directionality of EB3-GFP movements in dendrites and axons reflects the highly specific microtubule organization in neurons. Together, these results suggest that local microtubule polymerization contributes to the formation of the microtubule network in all neuronal compartments. We propose that similar mechanisms underlie the specific association of CLIPs and EB1-related proteins with the ends of growing microtubules in non-neuronal and neuronal cells.