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At least 217 records · Page 12Linked to original sources
PubMed2003

Cutaneous cysts: a plea for systematic analysis.

So-called cutaneous cysts are extremely frequent tumours that could need surgical attention. Most of the time, due to their quite pathognomonic clinical presentation and indolent course, they are simply enucleated. Often, the clinical diagnosis is easily confirmed at surgery by the typical appearance of a cystic formation filled with a creamy fluid. It is frequent for such "typical" lesions to escape histological investigation following removal. However, some mimicking lesions could also be found as "cutaneous cysts" and have quite different prognoses. This paper present five patients with such lesions, three basal cell carcinomas, one benign proliferating trichilemmal cyst and a malignant proliferating trichilemmal cyst. None of the lesions was clinically distinguishable from a classical epidermis cyst.

Adolescent↗
PubMed2006

Conclusiveness of the Cochrane Neonatal Reviews: a systematic analysis.

AIM: To assess the conclusiveness of the Cochrane Neonatal Reviews (CNRs). We tested the hypotheses that: 1) the majority of the reviews is inconclusive; 2) the majority of reviews recognizes the need for further studies; 3) the ability to reach a conclusion is dependent upon both the number of studies and the number of patients. We also aimed to determine whether the conclusiveness of the CNRs was affected by time. METHODS: We selected CNRs available in the Cochrane Library in June 2004. The number of randomized clinical trials (RCTs) found, number of RCTs included for analysis, number of patients enrolled, the stated need for further studies, and the conclusiveness of CNRs were recorded. RESULTS: Out of 170 CNRs, 67.7% were conclusive. The average number of articles was similar, but the total number of patients enrolled was three times higher in the conclusive CNRs. The percentage of articles included in conclusive studies was significantly higher than in inconclusive ones. The vast majority of CNRs recognized the need for further studies. The number of studies included correlated significantly with the total number of patients included. The percentage of conclusive CNRs correlated negatively with year of publication. CONCLUSION: The majority of CNRs is conclusive, but emphasizes the need for further studies. The ability of a CNR to reach a conclusion is affected by the cumulative sample size and by the number of studies performed. The probability of a newer review to be conclusive is lower than that of an older review.

Humans↗
PubMed2006

Consolidation therapy for adult acute myeloid leukemia: a systematic analysis according to evidence based medicine.

Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.

Adult↗
PubMed2003

Molecular systematic analysis reveals cryptic tertiary diversification of a widespread tropical rain forest tree.

The broad geographic range of many Neotropical rain forest tree species implies excellent dispersal abilities or range establishment that preceded the formation of current dispersal barriers. In order to initiate historical analyses of such widespread Neotropical trees, we sequenced the nuclear ribosomal spacer (ITS) region of Symphonia globulifera L. f. (Clusiaceae) from populations spanning the Neotropics and western Africa. This rain forest tree has left unmistakable Miocene fossils in Mesoamerica (15.5-18.2 Ma) and in South America ( approximately 15 Ma). Although marine dispersal of S. globulifera is considered improbable, our study establishes three marine dispersal events leading to the colonization of Mesoamerica, the Amazon basin, and the West Indies, thus supporting the paleontological data. Our phylogeographic analysis revealed the spatial extent of the three Neotropical S. globulifera clades, which represent trans-Andes (Mesoamerica+west Ecuador), cis-Andes (Amazonia+Guiana), and the West Indies. Strong phylogeographic structure found among trans-Andean populations of S. globulifera stands in contrast to an absence of ITS nucleotide variation across the Amazon basin and indicates profound regional differences in the demographic history of this rain forest tree. Drawing from these results, we provide a historical biogeographic hypothesis to account for differences in the patterns of beta diversity within Mesoamerican and Amazonian forests.

Africa↗
PubMed1993

Systematic analysis of antisense RNA inhibition of myosin II heavy-chain gene expression in Dictyostelium discoideum.

The powerful potential of antisense nucleotide inhibition of gene expression is presently being exploited in many biological systems. Although use of the technique is widespread, little is known about the variables that contribute to experimental success. We sought to define those variables that affect inhibition of myosin II heavy-chain (MIIHC) gene expression by stable nuclear-derived antisense RNAs in Dictyostelium discoideum. Different fragments of the MIIHC gene cloned in the antisense orientation into several transformation vectors were introduced into cells, and the accumulation of MIIHC protein and mRNA was examined. Inhibition of expression ranged from slight to virtually complete, and depended only on the specific gene fragment used to generate the antisense RNA. Fragments of the 3' end of the gene were the most effective and resulted in almost complete inhibition, whereas 5' fragments gave very little reduction. The severity of the morphological phenotypes associated with MIIHC depletion reflected the different levels of MIIHC in the transformants. Important implications for the design of antisense vectors suggested by these results are discussed.

Animals↗
PubMed1996

Systematic analysis of repeated gene delivery into animal lungs with a recombinant adenovirus vector.

Adenovirus-based vectors are promising candidates for genetic therapy of cystic fibrosis (CF). Because adenoviruses naturally infect airway cells, they grow to very high titers, and the transgenes carried by the adenoviruses are expressed at high levels. In addition, adenoviruses are relatively safe because the disease caused by the wild-type virus is self-limiting. One disadvantage of adenovirual vectors is that the transgene expression would be transient because adenoviruses do not integrate their DNA into the genome of the host cells. Adenoviral gene delivery into the lungs is also complicated by the anatomy of the airways and the defense mechanisms of the recipient. To assess the feasibility of adenovirus-mediated gene therapy for CF, a recombinant adenovirus carrying a lacZ gene was delivered into animal lungs to study the efficiency and cellular distribution of gene transfer, the duration of gene expression, the possible histopathology of the lungs after gene transfer, and the efficacy of repeated administrations of the viral agent. The results of these studies demonstrate that (i) efficient gene transfer into animal lungs can be achieved; (ii) a near-homogenous delivery of the vectors can be achieved by airway instillation, although the pattern of transduction varies among individual animals; (iii) pathological effects are generally mild in CD1 mice; (iv) gene expression is transient; (v) repetitive gene transfer is achievable, but becomes progressively less efficient, and (vi) immune responses are induced against both the viral and transgene products.

Adenoviridae↗
PubMed2004

Predicting gene function through systematic analysis and quality assessment of high-throughput data.

MOTIVATION: Determining gene function is an important challenge arising from the availability of whole genome sequences. Until recently, approaches based on sequence homology were the only high-throughput method for predicting gene function. Use of high-throughput generated experimental data sets for determining gene function has been limited for several reasons. RESULTS: Here a new approach is presented for integration of high-throughput data sets, leading to prediction of function based on relationships supported by multiple types and sources of data. This is achieved with a database containing 125 different high-throughput data sets describing phenotypes, cellular localizations, protein interactions and mRNA expression levels from Saccharomyces cerevisiae, using a bit-vector representation and information content-based ranking. The approach takes characteristic and qualitative differences between the data sets into account, is highly flexible, efficient and scalable. Database queries result in predictions for 543 uncharacterized genes, based on multiple functional relationships each supported by at least three types of experimental data. Some of these are experimentally verified, further demonstrating their reliability. The results also generate insights into the relative merits of different data types and provide a coherent framework for functional genomic datamining. AVAILABILITY: Free availability over the Internet. CONTACT: f.c.p.holstege@med.uu.nl SUPPLEMENTARY INFORMATION: http://www.genomics.med.uu.nl/pub/pk/comb_gen_network.

Computer Simulation↗
PubMed1998

A systematic analysis of the factors that determine the strength of pre-mRNA splicing enhancers.

We find that the strength of splicing enhancers is determined by the relative activities of the bound serine-arginine (SR)-rich splicing factors, the number of SR proteins within the enhancer complex and the distance between the enhancer and the intron. Remarkably, the splicing activity of the bound SR proteins is directly proportional to the number of RS tetrapeptide sequences within the RS domain. Quantitative analysis of the effects of varying the distance between the enhancer and the intron revealed that the splicing efficiency is directly proportional to the calculated probability of a direct interaction between the enhancer complex and the 3' splice site. These data are consistent with a model in which splicing enhancers function by increasing the local concentration of SR proteins in the vicinity of the nearby intron through RNA looping.

Base Sequence↗
PubMed2003

Systematic analysis of essential yeast TAFs in genome-wide transcription and preinitiation complex assembly.

The general transcription factor TFIID is composed of the TATA box binding protein (TBP) and a set of conserved TBP-associated factors (TAFs). Here we report the completion of genome-wide expression profiling analyses of yeast strains bearing temperature-sensitive mutations in each of the 13 essential TAFs. The percentage of the yeast genome dependent on each TAF ranges from 3% (TAF2) to 59-61% (TAF9). Approximately 84% of yeast genes are dependent upon one or more TAFs and 16% of yeast genes are TAF independent. In addition, this complete analysis defines three distinct classes of yeast promoters whose transcriptional requirements for TAFs differ substantially. Using this collection of temperature-sensitive mutants, we show that in all cases the transcriptional dependence for a TAF can be explained by a requirement for TBP recruitment and assembly of the preinitiation complex (PIC). Unexpectedly, these assembly experiments reveal that TAF11 and TAF13 appear to provide the critical functional contacts with TBP during PIC assembly. Collectively, our results confirm and extend the proposal that individual TAFs have selective transcriptional roles and distinct functions.

Base Sequence↗
PubMed1999

Artefactual increasing frequency of omphaloceles in the Northern Netherlands: lessons for systematic analysis of apparent epidemics.

BACKGROUND: While monitoring birth defects in a registry, statistically significant increases in prevalence occasionally occur. In the European Registration Of Congenital Anomalies (EUROCAT) in the Northern Netherlands 20000 births are monitored every year. For omphaloceles, a steady increase in the prevalence from 0.86 per 10000 live- and stillbirths in 1981-1983 to 3.11 per 10000 live- and stillbirths in 1994 was seen in the three northern provinces of The Netherlands. METHODS: A stepwise enquiry into this increase, which included checking for misclassification and change in coding and ascertainment when necessary, was done. All cases of omphalocele and associated or similar birth defects registered at the EUROCAT registry were retrieved and if necessary recoded. RESULTS: This study showed that the increase reported previously was not a true time trend. A few cases of e.g. diastasis recti and trisomy 18 were misclassified. The prevalence in more recent years is comparable with that in the rest of Europe, whereas it used to be lower. There was an increase in isolated omphalocele, but the numbers are small. CONCLUSIONS: The stepwise enquiry described should be a standard procedure after noticing an increasing prevalence in a registry. A better subdivision, e.g. in isolated cases versus children with multiple congenital anomalies, before monitoring can contribute to a lower number of false positive signals.

Congenital Abnormalities↗
PubMed2006

Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to the degree of prematurity.

BACKGROUND: Nulliparous women are at increased risk of spontaneous preterm birth. Other maternal and biochemical risk factors have also been described. However, it is unclear whether these associations are strong enough to offer clinically useful prediction. It is also unclear whether the predictive power of these factors varies in relation to the degree of prematurity. METHODS: The risk of spontaneous preterm birth associated with maternal characteristics and second trimester serum screening data was analysed in a dataset of 84 391 first births in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in the relative risk of preterm birth over the period 24-36 weeks was assessed using a test of the proportional hazards assumption. RESULTS: The risk of spontaneous preterm birth was positively associated with maternal serum levels of alpha-fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions, smoking, and being unmarried and was negatively associated with height and body mass index. The risk of preterm birth at 24-28 weeks, but not later gestations, was increased in association with maternal levels of human chorionic gonadotrophin >95th percentile, maternal age <20, and two or more previous miscarriages. The area under the receiver operating characterise curve (95% CI) for models based on these factors was 0.67 (0.63-0.71) for 24-28 weeks, 0.65 (0.62-0.68) for 29-32 weeks, and 0.62 (0.61-0.63) for 33-36 weeks. CONCLUSIONS: Time to event analytic methods can identify factors that are differentially associated with spontaneous preterm birth according to the degree of prematurity. However, models based on maternal and biochemical data perform poorly as a screening test for any degree of spontaneous preterm birth.

Adult↗
PubMedDate not supplied

Systematic analysis of solvents and other volatile substances by gas chromatography.

Four column packings for screening volatiles in biological material by gas chromatography are evaluated. Retention data are standardized by the calculation of retention indices, and packing materials are compared by discriminating power and identification power. A combination of 5% Carbowax 20M on Carbopack B and 0.3% Carbowax 20M on Carbopack C appears to be best suited for screening. Hydroxy-n-alkanes are used as reference substances for the calculation of retention indices.

Chromatography, Gas↗
PubMedDate not supplied

Systematic analysis of stimulants and narcotic analgesics by gas chromatography with nitrogen specific detection and mass spectrometry.

The recovery data of 40 doping agents from human urine were evaluated. Retention data were standardized by the calculation of relative retention times using N,N-diisopropyl-n-dodecane as the internal standard. The relative standard deviations of retention times were less than 0.5% for the within batch analyses and less than 0.8% for the day-to-day analyses. Good recoveries (greater than 70%) were observed for most of the drugs.

Analgesics, Opioid↗
PubMedDate not supplied

Systematic analysis of diuretic doping agents by HPLC screening and GC/MS confirmation.

The simultaneous analysis of diuretic agents by reversed-phase liquid chromatography with a diode-array detector (DAD) was performed by using a gradient elution with acetonitrile and phosphate buffer on a Hypersil-ODS column. For the spiked urine the extraction recovery of solid-phase extraction (SPE) using Sep-Pak C18 cartridge was compared with that of liquid-liquid extraction (LLE) with diethyl ether at various pH. The standard calibration curves were linear from 0.20-20.0 micrograms/mL for all diuretic agents except amiloride, 1.0-20.0 micrograms/mL, and the detection limit was about 0.2 micrograms/mL for 3 mL of urine, except that of amiloride, which was 1.0 micrograms/mL. The confirmation analysis was performed by gas chromatography/mass spectrometry (GC/MS) following methylation. The characteristic mass fragment ions obtained by electron-impact (EI) ionization (70 eV) provided identification of each diuretic agent.

Adult↗
PubMed2004

Regulation of high-affinity sulphate transporters in plants: towards systematic analysis of sulphur signalling and regulation.

Plants require the function of plasma membrane-bound sulphate transporters for the initial uptake of inorganic sulphate. Part of this fundamental process is the energy-dependent proton/sulphate co-transport systems that are located in the surface cell layers of roots. During sulphur limitation, plants are able to activate the expression of sulphate transporters that facilitate the uptake of sulphate in roots. SULTR1;1 and SULTR1;2 are suggested to be the essential components of the sulphate uptake system in Arabidopsis roots. The physiological importance of SULTR1;1 and SULTR1;2 is supported by characteristics that can cope with sulphur deficiency: they were (i) functional high-affinity sulphate transporters; (ii) induced by sulphur limitation at the mRNA levels; and (iii) predominantly localized in the root hairs, epidermis, and cortex. The expression of high-affinity sulphate transporters was primarily regulated by sulphur in a promoter-dependent manner. Aside from the sulphur-specific regulation, the induction of SULTR1;1 and SULTR1;2 high-affinity sulphate transporters by sulphur limitation was dependent on the supply of carbon and nitrogen. In this review, the application of SULTR promoter-GFP systems for the analysis of regulatory pathways of sulphate acquisition in plants is described.

Anion Transport Proteins↗
PubMed1991

Construction of an ordered clone bank and systematic analysis of the whole transcripts of chromosome VI of Saccharomyces cerevisiae.

By comparing sequences of restriction enzyme cleavage sites and their distance data, we sorted 384 lambda phage clones containing segments of chromosome VI of S. cerevisiae and constructed an ordered clone bank for this chromosome. The physical length of this bank is 269.7 kb. The bank contains the entire chromosome including the left telomere, but it is not certain whether it contains the right telomere as well. To estimate the number of genes present on this chromosome, we performed a series of Northern hybridization experiments using 157 restriction enzyme fragments prepared from the bank as hybridization probes and total poly(A)+ RNA from vegetatively growing cells. Thus, 97 distinct transcripts were identified. The relative abundance levels of individual transcripts were measured by comparing their band intensity with that of the RPO41 transcript. It was found that the transcripts from the genes located in the telomeric and centromeric regions are less abundant as compared to those from the genes in the central regions of both arms.

Blotting, Northern↗
PubMed1997

A systematic analysis of how medical school characteristics relate to graduates' choices of primary care specialties.

PURPOSE: To examine medical school characteristics, in particular federal funding for biomedical research, as they relate to the graduates' choices of family medicine, general internal medicine, general pediatrics, or all three specialties. METHOD: Data were collected for 121 U.S. medical schools, including information on funding, faculty, curricula, and other school characteristics. In addition, a questionnaire was mailed to the schools requesting information about non-federal funding for primary care, primary care department characteristics, and primary care representation on the admission, curriculum, and promotion and tenure committees. Analyses were carried out separately for each specialty and for all three combined. The first multiple regression analysis was done to predict specialty choice (proximate predictors), the second to predict the predictors of specialty choice (intermediate predictors), and the third to predict those predictors (distal predictors). RESULTS: Prediction was best for family medicine practice. Interest at matriculation and required third-year and fourth-year time in primary care were the two best proximate predictors. The best predictors of initial interest were the percentage of rural students and special programs for primary care, while the best predictors of required time in primary care were funding for family medicine and the percentage of faculty in family medicine (intermediate predictors). The best predictor of the percentage of faculty in family medicine was funding for family medicine (distal predictor). CONCLUSION: The results suggest that the most effective way to increase the number of physicians with generalist practices is to increase the number of students interested in a family medicine career at matriculation.

Career Choice↗