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PubMed2004

[Prognosis of hepatocellular carcinoma according to new staging classifications].

BACKGROUND AND OBJECTIVE: We investigated prognostic factors and survival of patients with hepatocellular carcinoma (HCC) in North-Germany. Established staging systems (Child-Pugh, Okuda and UICC classification) were compared with new prognostic scores from Italy (CLIP) and Spain (BCLC). PATIENTS AND METHODS: The clinical course of 62 consecutive patients (34-82 years, 48 males, 14 females) with HCC observed in the Medical School of Hannover from October 1996 to September 1998 were retrospectively analyzed. The patients were classified according to the staging systems of Child Pugh, Okuda, UICC, CLIP and BCLC. Follow-up ended on December 31 (st) 2001. RESULTS: Overall median survival was 11,3 (1 - 59,5) months. At univariate analysis (log-rank test) Okuda, UICC, CLIP and BCLC Score were each associated with a shorter survival. In contrast Child Pugh score provided no significant prognostication. By multiple regression analysis (Cox regression analysis), only the CLIP and UICC score and chronic hepatitis B infection were shown to be independent risk factors. CONCLUSION: Our investigations indicate, that the CLIP and UICC classifications identified those patients with the best prognosis and they, as well as chronic hepatitis C, were shown to be independent risk factors.

Adult↗

PubMed2001

A rapid classification protocol for the CATH Domain Database to support structural genomics.

In order to support the structural genomic initiatives, both by rapidly classifying newly determined structures and by suggesting suitable targets for structure determination, we have recently developed several new protocols for classifying structures in the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath). These aim to increase the speed of classification of new structures using fast algorithms for structure comparison (GRATH) and to improve the sensitivity in recognising distant structural relatives by incorporating sequence information from relatives in the genomes (DomainFinder). In order to ensure the integrity of the database given the expected increase in data, the CATH Protein Family Database (CATH-PFDB), which currently includes 25,320 structural domains and a further 160,000 sequence relatives has now been installed in a relational ORACLE database. This was essential for developing more rigorous validation procedures and for allowing efficient querying of the database, particularly for genome analysis. The associated Dictionary of Homologous Superfamilies [Bray,J.E., Todd,A.E., Pearl,F.M.G., Thornton,J.M. and Orengo,C.A. (2000) Protein Eng., 13, 153-165], which provides multiple structural alignments and functional information to assist in assigning new relatives, has also been expanded recently and now includes information for 903 homologous superfamilies. In order to improve coverage of known structures, preliminary classification levels are now provided for new structures at interim stages in the classification protocol. Since a large proportion of new structures can be rapidly classified using profile-based sequence analysis [e.g. PSI-BLAST: Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. (1997) Nucleic Acids Res., 25, 3389-3402], this provides preliminary classification for easily recognisable homologues, which in the latest release of CATH (version 1.7) represented nearly three-quarters of the non-identical structures.

Computational Biology↗

PubMed1996

Three distinct neuronal phenotypes exist in embryonic rat hippocampal neurons cultured in basic fibroblast growth factor.

The possibility that neurons cultured in basic fibroblast growth factor (bFGF) are heterogeneous raises concerns about their subsequent use in gene transfection and transplantation studies. We have examined the fate of embryonic hippocampal neurons in bFGF culture, and now conclude that these cells are not only heterogeneous, but possess neurons of various stages of development. Morphological and immunocytochemical analysis reveal three distinct developmental classes of neurons are present in extended bFGF culture. This tripartite classification is supported by electrophysiological analysis, which reveals that upon depolarization, neurons with precursor and juvenile neuron morphologies are unable to fire action potentials. The third class of neurons, which resemble age-matched polarized neurons in standard serum culture, fired multiple action potentials indicative of a mature phenotype. These data show neurons at multiple developmental stages co-exist in bFGF culture, and provide an experimental basis for their classification.

Action Potentials↗

PubMed2005

[A pilot study of spectrum of gene expression of acute leukemia].

OBJECTIVE: To investigate the gene expression of acute leukemia so as to study the pathogenesis of leukemia. METHODS: Five ml of bone marrow was collected from 22 patients with leukemia, 15 males and 7 females, aged 15-86, 17 with acute myelocytic leukemia, 4 with acute lymphocytic leukemia, and 1 with AHL. Mononuclear cells were isolated. Total RNA was extracted and mRNA was purified. DNA microarray technique with 12 848 genes was used to analyze the gene expression profiles. RESULTS: The predicted 45 genes were enormously expressed in 21 patients with acute leukemia, which were consistent with the ALL and AML classification standards reported by Golub and others. 7 genes which were overexpressed in multiple-resistant cell line K562-n/VCR were also overexpressed in 6 cases of refractory acute leukemia. Further analysis showed that 31 genes were upregulated in AML (M(4)-M(6)) and ALL but downregulated in AML (M(1)-M(3)). CONCLUSION: This results support the standard Golub has put forward. The reason that adult patients with ALL and subtypes of AML (M(4)-M(6)) have poorer prognosis in comparison with AMLM(1)-M(3) is attributed to alterations in gene expression. Primary drug resistance may be the major characteristics of refractory leukemia. Analysis of gene expression profile in acute leukemia is significant for classification and prognosis.

Adolescent↗

PubMed2006

A comparison of transcriptomic and metabonomic technologies for identifying biomarkers predictive of two-year rodent cancer bioassays.

Two-year rodent bioassays play a central role in evaluating the carcinogenic potential of both commercial products and environmental contaminants. The bioassays are expensive and time consuming, requiring years to complete and costing $2-4 million. In this study, we compare transcriptomic and metabonomic technologies for discovering biomarkers that can efficiently and economically identify chemical carcinogens without performing a standard two-year rodent bioassay. Animals were exposed subchronically to two chemicals (one genotoxic and one nongenotoxic) that were positive for lung and liver tumors in a standard two-year bioassay, two chemicals that were negative, and two control groups. Microarray analysis performed on liver and lung tissues identified multiple biomarkers in each tissue that could discriminate between carcinogenic and noncarcinogenic treatments. The discriminating biomarkers shared a common expression profile among carcinogenic treatments despite different genotoxicity categories and potential modes of action, suggesting that they reflect underlying cellular changes in the transition toward neoplasia. Statistical classification analysis exhibited 100% accuracy in both tissues when the number of genes was less than 5000. Additional genes reduced the predictive accuracy of the model. Serum samples were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy, and chemical-specific metabolites were removed from the spectra. The statistical classification analysis of the endogenous serum metabolites showed relatively low predictive accuracy with few metabolites in the model, but the accuracy increased to a maximum of 94% when all metabolites were added. These results suggest that individual endogenous metabolites are relatively poor biomarkers, but the metabolite profile as a whole is altered following carcinogen treatment.

Animals↗

PubMed2006

Clinical prediction tool to identify patients with Pseudomonas aeruginosa respiratory tract infections at greatest risk for multidrug resistance.

Despite the increasing prevalence of multiple-drug-resistant (MDR) Pseudomonas aeruginosa, the factors predictive of MDR have not been extensively explored. We sought to examine factors predictive of MDR among patients with P. aeruginosa respiratory tract infections and to develop a tool to estimate the probability of MDR among such high-risk patients. This was a single-site, case-control study of patients with P. aeruginosa respiratory tract infections. Multiple-drug resistance was defined as resistance to four or more antipseudomonal antimicrobial classes. Clinical data on demographics, antibiotic history, and microbiology were collected. Classification and regression tree analysis (CART) was used to identify the duration of antibiotic exposure associated with MDR P. aeruginosa. Log-binomial regression was used to model the probability of MDR P. aeruginosa. Among 351 P. aeruginosa-infected patients, the proportion of MDR P. aeruginosa was 35%. A significant relationship between prior antibiotic exposure and MDR P. aeruginosa was found for all of the antipseudomonal antibiotics studied, but the duration of prior exposure associated with MDR varied between antibiotic classes; the shortest prior exposure duration was observed for carbapenems and fluoroquinolones, and the longest duration was noted for cefepime and piperacillin-tazobactam. Within the final model, the predicted MDR P. aeruginosa likelihood was most dependent upon length of hospital stay, prior culture sample collection, and number of CART-derived prior antibiotic exposures. A history of a prolonged hospital stay and exposure to antipseudomonal antibiotics predicts multidrug resistance among patients with P. aeruginosa respiratory tract infections at our institution. Identifying these risk factors enabled us to develop a prediction tool to assess the risk of resistance and thus guide empirical antibiotic therapy.

Adult↗

PubMed1997

Prognostic value of objective semen parameters in an in vitro fertilization program.

PURPOSE: The basic semen parameters seem to have a limited predictive value in male fertility. Could other objective sperm analyses be helpful in the choice of the most adapted assisted procreation technique? METHODS: This study concerns 78 infertile couples with insemination failures. For each semen, 21 objective parameters are analyzed in fresh semen and after sperm selection procedure. The 78 couples are then included in an IVF protocol and classified into two groups: fertile (at least one cleaved embryo is obtained) and infertile. RESULTS: Using multiple variant discriminant factorial analysis, we have found nine nonconventional parameters which induce us to define two classes of semen. These two classes fit with the classification into fertile and infertile groups in 74.4% of the cases. CONCLUSIONS: So these parameters allow us to predict the chance of obtaining embryos during an IVF trial and to choose for each couple the most appropriate technique: IVF or ICSI.

Acrosin↗

PubMed2005

Analysis of factors influencing hepatocellular carcinoma detection: efficient use of computed tomography during arterial portography and during hepatic arteriography.

BACKGROUND: This study was performed to investigate the situations in which computed tomography (CT) combined with arterial portography and hepatic arteriography surpassed dynamic CT in the detection of hepatocellular carcinoma. METHODS: Computed tomography combined with arterial portography and hepatic arteriography was performed on 137 patients with chronic hepatitis (92 men and 45 women; mean age, 66.5 years) with hepatocellular carcinoma (HCC) as revealed or suspected by dynamic CT. We analyzed the clinical factors leading to the discovery of additional HCC lesions on CT combined with arterial portography and hepatic arteriography that were undetected by dynamic CT. RESULTS: Computed tomography combined with arterial portography and hepatic arteriography detected additional HCC lesions that had not been revealed by dynamic CT in 33 of 137 patients. Univariate analysis revealed that in the event of HCC recurrence (vs. primary), multiple HCC lesions detected by dynamic CT (vs. single) and decreased liver function (Child's classification B/C vs. A) significantly favored the additional detection of HCC lesions. Multivariate logistic regression indicated that recurrence was the strongest predicting factor for finding additional lesions on computed tomography combined with arterial portography and hepatic arteriography. CONCLUSIONS: Computed tomography combined with arterial portography and hepatic arteriography is capable of finding additional HCC lesions undetectable by dynamic CT, especially in advanced cases such as HCC recurrence, which may affect the choice of treatment.

Aged↗

PubMed2000

Molecular analysis of ribosomal RNA gene of red tide algae obtained from the seto inland sea.

Eleven clones from five species of the planktonic microalgae, (Chattonella antiqua, Chattonella marina, Heterosigma akashiwo, Alexandrium catenella, and Scrippsiella trochoidea), which were collected from the Seto Inland Sea in Japan and from Thailand, were subjected to nucleotide sequence analysis of the D1/D2 domain of the large subunit (LSU) of their ribosomal RNA genes. After amplification by polymerase chain reaction using degenerated primers, whole-nucleotide sequences for the D1/D2 domains of the LSU rRNA gene of 11 microalgae were analyzed. Phylogenic tree analysis using these nucleotide sequences showed each species located in a cluster corresponding to its morphological classification. The nucleotide sequence data for Chattonella spp. suggest that multiple clones of both Chattonella antiqua and Chattonella marina are present in the Seto Inland Sea and that red tide blooms of Chattonella spp. in different years may have contained different clones.

Journal Article↗

PubMed1998

Determining the number of independent sources of the EEG: a simulation study on information criteria.

The separation of signal and noise is an important problem in the analysis of EEG and MEG data. Furthermore, many source localisation strategies need the number of independent signal components as input parameter (e.g., dipole fit, multiple signal classification). Information criteria offer a relatively objective way to separate the space spanned by the principal components of the data covariance matrix into a signal and a noise part. Eighteen such criteria were extensively tested by simulations. They differ with respect to the statistical model of the data, the assumptions on the noise, and the correction term. In the simulations, different dipole sources were used to generate EEG, which was then distorted by Gaussian correlated or uncorrelated noise. The noise level, the accuracy of the noise covariance matrix used by the criteria, the numbers of channels and time samples, and the stochastic or deterministic nature of the source waveforms were varied. The performance of the criteria was very variable. For each criterion, limits for the noise level and the relative inaccuracy of the noise covariance matrix could be established. Taking more channels or time steps did increase the criteria's ability to tolerate noise, but at the same time, made them more vulnerable to inaccuracies in the (estimated) noise covariance matrices. Out of the eighteen criteria investigated, we recommend two criteria that are best suited for the cases of (1) high noise and accurate covariances and (2) low noise and less accurate covariances.

Artifacts↗

PubMed1979

The prediction of swimming performance in competition from behavioral information.

The swimming performances of the Canadian Team at the 1976 Olympic Games were categorized as being improved or worse than previous best times in the events contested. The two groups had been previously assessed on the Psychological Inventories for Competitive Swimmers. A stepwise multiple-discriminant analysis of the inventory responses revealed that 13 test questions produced a perfect discrimination of group membership. The resultant discriminant functions for predicting performance classification were applied to the test responses of 157 swimmers at the 1977 Canadian Winter National Swimming Championships. Using the same performance classification criteria the accuracy of prediction was not better than chance in three of four sex by performance classifications. This yielded a failure to locate a set of behavioral factors which determine swimming performance improvements in elite competitive circumstances. The possibility of sets of factors which do not discriminate between performances in similar environments or between similar groups of swimmers was raised.

Behavior↗

PubMed2003

Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data.

BACKGROUND: Pulmonary thromboembolism (PTE) is a common clinical problem that is associated with substantial morbidity and mortality. Estimates of PTE mortality and predictions of PTE trends have varied widely. These estimates play a role in the planning of national health strategies. The analysis of pulmonary embolism mortality trends and comorbidities may elucidate how well we treat and prevent the disease as well as identify additional risk factors. METHODS: We analyzed PTE (International Classification of Diseases, Ninth Revision code 415.1) as reported on death certificates in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics from 1979 to 1998. RESULTS: Of all the 42932973 decedents, 572773 (1.3%) had PTE listed on their death certificates and 194389 of these (33.9%) had PTE as the underlying cause of death. The age-adjusted rate of deaths with PTE decreased from 191 per million in 1979 to 94 per million in 1998 overall, decreasing 56% for men and 46% for women. During the study period, the age-adjusted mortality rates for blacks were consistently 50% higher than those for whites, and those for whites were 50% higher than those for people of other races (Asian, American Indian, etc). Within racial strata, mortality rates were consistently 20% to 30% higher among men than among women. Conditions that were of higher likelihood in persons who died with PTE included thrombophlebitis, fractures, trauma, postoperative complications, certain cancers, and the inflammatory bowel diseases. CONCLUSIONS: Mortality with PTE in the United States has decreased during the 20-year period. The mortality rates between men and women and between racial groups vary substantially. These findings may be useful in better directing preventive therapy efforts.

Adolescent↗

PubMed1999

Risk stratification for coronary bypass surgery in patients with left ventricular dysfunction: analysis of the coronary artery bypass grafting patch trial database.

BACKGROUND: Preoperative characteristics may influence morbidity and mortality in patients undergoing coronary artery bypass grafting (CABG). The CABG Patch Trial was designed to assess the impact of prophylactic insertion of an implantable cardioverter-defibrillator in patients undergoing high-risk CABG. This database was used to investigate the influence of symptomatic congestive heart failure (CHF) and angina on morbidity and mortality in CABG patients with ventricular dysfunction. METHODS AND RESULTS: Data were analyzed for 900 randomized patients with an ejection fraction </=35% and an abnormal signal-averaged ECG. Single-variable and stepwise multiple logistic regression analyses were used for mortality and length-of-stay (LOS) data. Severity of CHF and angina was graded by the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications, respectively. Perioperative mortality was 3.5% in 454 patients without clinical signs of heart failure versus 7.7% in 443 patients with NYHA class I to IV heart failure (P=0.018). By multiple logistic regression analysis, mortality was significantly higher in patients with preoperative symptomatic (NYHA class I to IV) heart failure (odds ratio, 2.4; P=0.01) or reoperation (odds ratio, 3.8; P<0.0001). Mortality was not significantly influenced by age, sex, the presence or severity of angina, hypertension, left main coronary artery disease, pulmonary disease, or severity of CHF (although LOS was increased 0.7 days per NYHA class). Patients with a history of stroke had a higher rate of perioperative stroke (16.4% versus 3.6%, P=0.001) and an increased LOS (by 3.5 days). CONCLUSIONS: Symptomatic heart failure and reoperation are predictors of increased operative mortality in patients with ventricular dysfunction and a positive signal-averaged ECG. Conversely, patients without heart failure symptoms may undergo CABG with relatively low mortality despite low ejection fraction. LOS is prolonged significantly by advanced age, history of stroke, and the presence and severity of heart failure.

Adult↗

PubMed1987

Rationale for the histological spectrum of tuberculosis. A basis for classification.

There is need to re-appraise the cellular response to Mycobacterium tuberculosis. Histological analysis of 54 untreated patients with established disease demonstrated a continuous spectrum of tissue responses in which six groups correlated with evidence of resistance to bacterial multiplication. A predominance of cases in the two middle groups (82%) signified an immunological equilibrium in middle grade resistant patients that is absent in related diseases such as leprosy and cutaneous leishmaniasis. The dominant feature was necrosis, which increased progressively across the spectrum. Its form varied from minimal fibrinoid change, through fine eosinophilic necrosis, to basophilic necrosis characterized by neutrophil karyorrhexis, and finally to an almost acellular lesion with many bacilli. Cytological differentiation of the granuloma was of subsidiary significance, mature epithelioid cells being found only in high resistant cases. No correlation was found for the number of lymphocytes. This classification is thought to be an accurate reflection of the immune state in relation to antigenic load. It raises a hitherto unconsidered possibility that "caseation", a loosely applied macroscopic term, may embrace immunologically distinct states. The classification of multiple lesions was consistent. Histology offers a promising basis for further immunopathological investigation.

Cell Nucleus↗

PubMed1994

DNA sequence analysis using hierarchical ART-based Classification Networks.

Adaptive resonance theory (ART) describes a class of artificial neural network architectures that act as classification tools which self-organize, work in realtime, and require no retraining to classify novel sequences. We have adapted ART networks to provide support to scientists attempting to categorize tandem repeat DNA fragments from Onchocerca volvulus. In this approach, sequences of DNA fragments are presented to multiple ART-based networks which are linked together into two (or more) tiers; the first provides coarse sequence classification while the subsequent tiers refine the classifications as needed. The overall rating of the resulting classification of fragments is measured using statistical techniques based on those introduced by Zimmerman, et al. (1994) to validate results from traditional phylogenetic analysis. Tests of the Hierarchical ART-based Classification Network, or HABclass network, indicate its value as a fast, easy-to-use classification tool which adapts to new data without retraining on previously classified data.

Algorithms↗

PubMed2006

The MPI Bioinformatics Toolkit for protein sequence analysis.

The MPI Bioinformatics Toolkit is an interactive web service which offers access to a great variety of public and in-house bioinformatics tools. They are grouped into different sections that support sequence searches, multiple alignment, secondary and tertiary structure prediction and classification. Several public tools are offered in customized versions that extend their functionality. For example, PSI-BLAST can be run against regularly updated standard databases, customized user databases or selectable sets of genomes. Another tool, Quick2D, integrates the results of various secondary structure, transmembrane and disorder prediction programs into one view. The Toolkit provides a friendly and intuitive user interface with an online help facility. As a key feature, various tools are interconnected so that the results of one tool can be forwarded to other tools. One could run PSI-BLAST, parse out a multiple alignment of selected hits and send the results to a cluster analysis tool. The Toolkit framework and the tools developed in-house will be packaged and freely available under the GNU Lesser General Public Licence (LGPL). The Toolkit can be accessed at http://toolkit.tuebingen.mpg.de.

Computational Biology↗

PubMed1990

Transformation of multitrait to unitrait mixed model analysis of data with multiple random effects.

An algorithm for transforming a multitrait into a unitrait analysis was presented for a mixed model that has equal design matrices for t traits and contains more than one random classification. The class of models was restricted to those in which the covariance matrices for all random effects including the residual can be diagonalized simultaneously. A variation of this assumption was called the common principal component by Flury. As a result of the transformation, setting up and solving the laborious t trait mixed model equations becomes a simple matter of setting up and solving the unitrait mixed model equations separately for each of the t transformed traits. The present procedure would not only simplify computer programming but more importantly it would drastically reduce central processing unit time and computer space requirements. A numerical example was given to illustrate this procedure of indirect multitrait analysis in comparison with direct multitrait analysis.

Algorithms↗

PubMed2002

[What prognostic factors correlate with activities of daily living (Barthel Index) 1 year after para-articular hip fracture? A prospective observational study].

UNLABELLED: The aim of this prospective study was to identify prognostic factors predicting post-operative outcome in patients one year after their hip fracture. METHODS: From October 1996 until September 1997 all patients (n = 98) treated for a hip fracture in our hospital were prospectively included into the study. Follow up was performed at three, six and twelve months after the injury. The main outcome variable was the activity of daily living measured by the Barthel-Index. An univariate analysis of the variables age, gender, ASA-classification, type of fracture and treatment, length of stay and rehabilitation was performed and all these variables were correlated with the Barthel-Index. A multiple logistic regression was performed for identification of prognostic factors predicting outcome. RESULTS: The one year lethality was 33% (n = 31). All patients younger than 75 years reached their preoperative activity level at one year follow up. Patients with age of 75 years or more experienced a reduction of their activities of daily living of 20%. The ADL-differences of both groups at the follow up after 3, 6 and 12 months showed a significant p-value (p < 0.001). The ADL-differences between the group of patients with or without a transfer to a specialized rehabilitation center were not significant. The multivariate analysis showed that the preoperative use of the Barthel-Index was the best prognostic factor for outcome until one year after the injury. CONCLUSION: The preoperative Barthel-Index should be seriously considered for therapeutic decision making in patients with hip fractures.

Activities of Daily Living↗