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p53 and cyclin D1 as prognostic factors in squamous cell carcinoma of the larynx.

OBJECTIVES/HYPOTHESIS: Proteins p53 and cyclin D1 play a crucial role in cell cycle control. Protein p53 mutations are one of the most common genetic alterations in human cancer, and cyclin D1 gene amplification has been found to be associated with poor prognosis in different types of tumors. Functional alterations of these proteins may play an important role both in the carcinogenesis of squamous carcinomas of the head and neck and in the clinical evolution of these tumors. The objective of the present study was to evaluate whether the presence of p53 and/or cyclin D1 proteins (detected by immunohistochemical analysis) could serve as relevant variables for the assessment of the prognosis of laryngeal squamous cell carcinoma. STUDY DESIGN: Retrospective multicentric study. METHODS: Paraffin-embedded biopsy specimens from 62 human epidermoid laryngeal carcinomas were randomly selected. The expression of p53 and cyclin D1 was examined by means of immunohistochemical analysis with a view to evaluating whether there is a correlation between the aberrant expression of these proteins and disease prognosis. RESULTS: In the sample, the presence of immunohistochemically detectable p53 is associated with shorter survival and disease-free intervals, as shown in Kaplan-Meier survival curve analysis. Indeed, multivariate statistical analysis revealed that the accumulation of p53 is an independent prognostic factor, which is associated with shorter survival. This association was not evident in the case of cyclin D1. CONCLUSION: A more precise prognosis of patients with laryngeal epidermoid carcinomas could be achieved by taking into account the presence of p53 (as assayed by immunohistochemical analysis) in biopsy tissue

Adult↗

Types, frequencies, and risk factors for complications after third molar extraction.

OBJECTIVES: The study objective was to identify the types, frequency, and risk factors for complications after third molar (M3) extractions. STUDY DESIGN: This retrospective cohort study consisted of patients who had 1 or more M3s removed between 1996 and 2001. Risk factors were grouped into demographic, general health, anatomic, and operative. Outcome variables were operative or inflammatory complications. Data were analyzed using descriptive, bivariate, and multivariate statistics. RESULTS: The study sample was composed of 583 patients (57.0% male) with a mean age of 26.4 +/- 8.4 years. The overall complication rate was 4.6%. Increasing age, a positive medical history, and the position of the M3 relative to the inferior alveolar nerve were associated with an increased risk for complications. CONCLUSION: While age, medical history, and M3 anatomy cannot be altered directly, these factors may be modified indirectly, resulting in a potential decrease for postoperative complications.

Adolescent↗

Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach.

BACKGROUND: Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships. The aim of this study was to investigate, using factor analysis, a clustering of pro-inflammatory markers, anti-inflammatory cytokines such as interleukin-10 (IL-10) and HDL cholesterol, and to determine their role in prediction of risk of recurrent coronary events in ACS patients. METHODS: We assessed 320 consecutive patients (236 men; 67 years; IQ 58-74 years) admitted with ACS. The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum CRP, fibrinogen, HDL cholesterol, IL-10, IL-18 and ICAM-1 levels were measured at study entry. We assessed independent predictors of the combined end-point during a 1-year follow-up using multiple logistic regression analysis. RESULTS: Factor analysis identified three clusters which were arbitrarily interpreted as (1) a "systemic inflammation" cluster with positive loadings of CRP and fibrinogen, (2) a "local inflammation-endothelial dysfunction" cluster with positive loadings of IL-18 and ICAM-1 and (3) an "anti-inflammation" cluster comprising IL-10 and HDL cholesterol. Only the "anti-inflammation" cluster was a significant predictor (OR 0.66, 95% CI: 0.49-0.89) of adverse cardiac events during a 1-year follow-up and remained significant (OR 0.65, 95% CI: 0.48-0.88) in a multivariate model that included all three factors. CONCLUSIONS: Although inflammatory markers such as CRP predict future cardiovascular events in ACS patients, when all inflammatory mediators are taken into account in a prospective analysis of risk, markers reflecting anti-inflammatory mechanisms are better prognostic markers.

Acute Disease↗

Histometrics: improvement of the dynamic range of fluorescently stained proteins resolved in electrophoretic gels using hyperspectral imaging.

Most image-based analyses, using absorbance or fluorescence of the spatial distribution of identifiable structures in complex biological systems, use only a very small number of dimensions of possible spectral data for the generation and interpretation of the image. We here extend the concepts of hyperspectral imaging, being developed in remote sensing, into analytical biotechnology. The massive volume of information contained in hyperspectral spectroscopic images requires multivariate analysis in order to extract the chemical and spatial information contained within the data. We here describe the use of multivariate statistical methods to map and quantify common protein staining fluorophores (SYPRO Red, Orange and Tangerine) in electrophoretic gels. Specifically, we find (a) that the 'background' underpinning limits of detection is due more to proteins that have not migrated properly than to impurities or to ineffective destaining, (b) the detailed mechanisms of staining of SYPRO red and orange are apparently not identical, and in particular (c) that these methods can provide two orders of magnitude improvement in the detection limit per pixel, to levels well below the limit observable optically.

Biotechnology↗

Characteristic electron microscopical projections of the small ribosomal subunit from Thermomyces lanuginosus.

Multivariate statistical analysis and hierarchical ascendant classification techniques have been used to sort electron images of small ribosomal subunits from the thermophilic fungus Thermomyces lanuginosus into their characteristic views. Three predominant modes of adsorption to the support were elucidated: right-lateral, left-lateral and asymmetric, showing reproducible detail approaching 1.8 nm resolution. The projections of the fungal complexes appeared almost identical to those of HeLa cells, rat liver and rabbit reticulocytes studied previously in this manner. This result contrasts with the greater variation in fine structural features observed between ribosomal subunits from different prokaryotic species.

Animals↗

Interferon-alpha therapy in HCV hepatitis: HLA phenotype and cirrhosis are independent predictors of clinical outcome.

Interferon-alpha therapy is effective in only approximately 20% of individuals with chronic HCV infection. A knowledge of the genetic and/or environmental factors that underlie this heterogeneity of response should provide useful predictors of clinical outcome. HCV infected patients and healthy subjects were selected from the expatriate Egyptian population living in Qatar, where chronic HCV infection poses a serious health problem. HCV infection was confirmed by ELISA and RT-PCR. Fifty five patients received interferon-alpha therapy for 6 months and their response was assessed by liver enzyme activity and histology of liver biopsies; the patient responses were followed during treatment and for 1 year afterwards. Twenty five patients were characterised as responders, and the remaining 30 as non-responders. All individuals in the study were typed for HLA class II alleles. Data were analysed by univariate and multivariate statistical methods. Expression of the HLA DR2 Major Histocompatibility class II allele is significantly associated with a beneficial response to interferon-alpha therapy in Egyptian patients (p < 0.005). This association is independent of cirrhosis, the absence of which also showed a significant association with response to therapy (p < 0.005). Our results therefore provide evidence that HLA DR2 is an important additional factor for predicting a long term response to interferon-alpha therapy in chronic HCV hepatitis.

Adult↗

Homeostatic signature of anabolic steroids in cattle using 1H-13C HMBC NMR metabonomics.

We used metabonomics to discriminate the urinary signature of different anabolic steroid treatments in cattle having different physiological backgrounds (age, sex, and race). (1)H-(13)C heteronuclear multiple bonding connectivity NMR spectroscopy and multivariate statistical methods reveal that metabolites such as trimethylamine-N-oxide, dimethylamine, hippurate, creatine, creatinine, and citrate characterize the biological fingerprint of anabolic treatment. These urinary biomarkers suggest an overall homeostatic adaptation in nitrogen and energy metabolism. From results obtained in this study, it is now possible to consider metabonomics as a complementary method usable to improve doping control strategies to detect fraudulent anabolic treatment in cattle since the oriented global metabolic response provides helpful discrimination.

Analysis of Variance↗

Treatment failure and dietary habits in women with breast cancer.

BACKGROUND: Epidemiological and experimental evidence suggests that breast cancer risk can be reduced by dietary measures. Study of the relationships between dietary habits and prognosis in patients with breast cancer is essential to the design of diet intervention trials. PURPOSE: Our purpose was to determine whether dietary habits are associated with disease-free survival in patients with breast cancer who have undergone treatment. METHODS: We interviewed 240 women about their dietary histories. These women were 50-65 years old and had pathological stage I-II breast cancer with subsequent follow-up for 4 years; 209 of these women were postmenopausal. Differences in dietary variables between groups of patients were analyzed with bivariate and multivariate statistical methods. RESULTS: Cancers were classified as estrogen receptor (ER) rich (> or = 0.10 fmol/micrograms of DNA) in 149 patients and as ER poor (< 0.10 fmol/micrograms of DNA) in 71 patients. Fifty-two patients had treatment failure during follow-up. The 30 patients with ER-rich tumors who had treatment failure reported higher intakes of total fat, saturated fatty acids, and polyunsaturated fatty acids than did the 119 patients with ER-rich tumors who did not have treatment failure. The multiple-odds ratio (OR) for treatment failure in these women was 1.08 for each 1% increment in percentage of total energy (E%) from total fat. For treatment failure within the first 2 years, the OR was 1.19 for each 1-mg increase in vitamin E intake per 10 megajoules of energy. In women with treatment failure 2-4 years after diagnosis, ORs were 1.13 and 1.23 for each E% increment in total fat or saturated fatty acids, respectively. No association between dietary habits and treatment failure was found for women with ER-poor cancers. There was a tendency to a dose-response relationship (in quartiles) between intake of saturated fatty acids and disease-free survival, but the observed differences were not statistically significant. CONCLUSIONS: Dietary habits at the time of diagnosis may affect prognosis, at least for patients with ER-rich breast cancers. Dietary fat may have an effect on growth or spread of breast cancer, both of which may vary according to type of fat. Total fat and saturated fatty acids were the dietary parameters most strongly associated with risk for treatment failure. IMPLICATIONS: Dietary intervention might serve as an adjuvant treatment to improve breast cancer prognosis.

Aged↗

Molecular diversity within Lactobacillus helveticus as revealed by genotypic characterization.

Lactobacillus helveticus is a homofermentative thermophilic lactic acid bacterium that is used in the manufacture of Swiss type and long-ripened Italian cheeses, such as Emmental, Grana, and Provolone cheeses. Substantial differences in several technologically important characteristics are found among L. helveticus strains isolated from natural dairy starter cultures. In the present study we investigated the genotypic diversity of 74 strains isolated from different dairy cultures used for manufacturing Grana and Provolone cheeses and six collection strains. A restriction fragment length polymorphism analysis of both total genomic DNA and the 16S rRNA gene (ribotyping) was used as genotypic fingerprinting. A multivariate statistical analysis of the data enabled us to identify significant genotypic heterogeneity in L. helveticus. We found that genotypic fingerprinting could be used to distinguish strains; in particular, it was possible to associate the presence of specific strain genotypes with dairy ecosystem sources (e.g., Grana or Provolone cheese). Our data contribute to the description of microbial heterogeneity in L. helveticus and provide a more solid basis for understanding the functional and ecological significance of the presence of different L. helveticus biotypes in natural dairy starter cultures.

Base Sequence↗

Effects of the novel neuroprotective agent, riluzole, on human brain function and behavior: I. Double-blind, placebo-controlled EEG mapping and psychometric studies under normoxia.

In a double-blind, placebo-controlled, crossover study, the encephalotropic and psychotropic properties of single oral doses of the novel neuroprotective agent, riluzole, were investigated utilizing EEG mapping and psychometry. Twenty healthy young volunteers received randomly at weekly intervals, placebo, 50, 100 and 200 mg riluzole. EEG recordings and evaluation of 9 noopsychic and 5 thymopsychic variables were carried out at 0, 2, 4, 6 and 8 h after oral drug administration. EEG maps on the multivariate analysis demonstrated that all three doses induced significant changes in human brain function, as compared with placebo, between 2 and 8 h, with effect only increasing slightly with dose. EEG maps on univariate analysis demonstrated generally an increase of delta/theta, decrease of alpha and beta power, as well as a slowing of the centroid of the total power spectrum, which suggests sedative properties of the drug. Only after the two highest doses at 6 h were some different findings observed. Multivariate statistics on psychometry failed to show any significant effects on the noopsyche, while for the thymopsyche, all three doses of riluzole produced a deterioration. The latter was characterized by a decrease in drive and wakefulness as well as deterioration in well-being, mood and affectivity. Thus, under normoxia, in all three doses riluzole produced neurophysiologically a sedative effect, accompanied at the behavioral level by a deterioration in the thymopsyche, which may be expected from a drug with antiglutamatergic effects in normals.

Adult↗

3D reconstruction and processing of volumetric data in cryo-electron tomography.

A software package is presented that was primarily developed for electron tomography in biological research. It comprises routines for preprocessing micrographs, CTF-correction of images of untilted and tilted specimens, alignment of tilt series, 3D reconstruction, spatial averaging of paracrystalline specimens, alignment of single particles or components of larger macromolecular assemblies, correlation averaging, multivariate statistical analysis, classification, and volume reassembly, in which molecular components in raw tomograms are replaced by averaged versions with higher signal-to-noise ratio. The emphasis for image analysis is placed on the processing of large sets of individual molecular volumes. The design philosophy of the software is both simplicity and interoperability, i.e. to write standalone programs for simple tasks that are combined through shell scripting to provide more complex functionality, and to communicate with other software via common image formats. This paper gives an overview of the current state of the programs and some applications to cryo-electron tomography.

Algorithms↗

Contribution of neuropsychological data to the prediction of temporal lobe epilepsy surgery outcome.

PURPOSE: We empirically examined the contribution of neuropsychological data to the prediction of postoperative seizure control relative to base rate information in an existing series of patients undergoing anterior temporal lobectomy (ATL). METHODS: A discriminant function predicting surgery outcome (seizure-free vs. non-seizure-free) was computed separately for samples of patients with left (n = 79) and right (n = 62) temporal lobectomy (LATL, RATL). Predictor variables included 14 measures tapping five neurocognitive domains. The predicted base rates were compared with the actual base rates in the two samples. Finally, overall predictive accuracy was examined in optimal versus suboptimal ATL patients. RESULTS: The base rate of seizure freedom in the LATL group was 74.70%; that in the RATL group was 66.10%. The predictive function for the LATL group achieved a hit rate of 80.00% and a positive predictive power of 92.11%. The function for the RATL group achieved a hit rate of 83.33% and a positive predictive power (PPP) of 89.66%. The overall predictive accuracy for the optimal group was only 55%, but that in the suboptimal group was 72%. CONCLUSIONS: Neuropsychological data used in a multivariate statistical fashion may be able to offer an incremental increase in the prediction of postoperative seizure freedom relative to existing base rates of surgery success in patients with ATL epilepsy. The use of neuropsychological data may be of greatest predictive value in a population of ATL candidates with suboptimal findings with a lower base rate of postoperative seizure freedom, but may actually reduce predictive accuracy in a group of ATL candidates from an optimal population with an already high base rate of surgical success.

Adult↗

Characterizing dynamic brain responses with fMRI: a multivariate approach.

In this paper we present a multivariate analysis of evoked hemodynamic responses and their spatiotemporal dynamics as measured with fast fMRI. This analysis uses standard multivariate statistics (MANCOVA) and the general linear model to make inferences about effects of interest and canonical variates analysis (CVA) to describe the important features of these effects. We have used these techniques to characterize the form of hemodynamic transients that are evoked during a cognitive or sensorimotor task. In particular we do not assume that the neural or hemodynamic response reaches some "steady state" but acknowledge that these physiological changes could show profound task-dependent adaptation and time-dependent changes during the task. To address this issue we have modeled hemodynamic responses using appropriate temporal basis functions and estimated their exact form within the general linear model using MANCOVA. We do not propose that this analysis is a particularly powerful way to make inferences about functional specialization (or more generally functional anatomy) because it only provides statistical inferences about the distributed (whole brain) responses evoked by different conditions. However, its application to characterizing the temporal aspects of evoked hemodynamic responses reveals some compelling and somewhat unexpected perspectives on transient but stereotyped responses to changes in cognitive or sensorimotor processing. The most remarkable observation is that these responses can be biphasic and show profound differences in their form depending on the extant task or condition. Furthermore these differences can be seen in the absence of changes in mean signal.

Arousal↗

Who are the elderly who never receive influenza immunization?

OBJECTIVE: This paper estimates the rates of lifetime nonreceipt of influenza immunization among elderly and examines variations in the lifetime nonreceipt of immunization by gender, race and ethnic group, socioeconomic status, access to health care, and health status. METHODS: Cross-sectional, nationally representative data on 5557 adults older than 50 years of age and living in the community from the 2000 Medical Expenditure Panel Survey are used. Lifetime nonreceipt of influenza immunization was analyzed with bivariate and multivariate statistical techniques. FINDINGS: Thirty-one percent of the elderly reported never receiving influenza immunization and 20% reported irregular immunization. Higher odds of lifetime nonreceipt of vaccination and irregular vaccination were seen among African-Americans, young-old, current smokers, and those with no usual source of care. CONCLUSIONS: Future campaigns to increase immunization rates should be tailored to target this hard-to-reach group of individuals.

Aged↗

Tobacco use and acculturation among Californians of Korean descent: a behavioral epidemiological analysis.

This study presents population estimates of cigarette use among adults of Korean descent residing in California. Data were drawn from telephone interviews with adults (N=2,830) developed from a random sampling of listed persons in California with Korean surnames. A total of 86% of attempted interviews were completed, and 85% of the interviews were conducted in Korean. Less acculturated men and more acculturated women reported higher present and predicted future rates of smoking after multivariate statistical controls were applied. Sharply divergent rates of cigarette use were found between the genders. Although men did not smoke their first cigarette or smoke cigarettes regularly earlier than women, both groups began smoking later than adults born in the United States. To be effective, tobacco intervention efforts must be tailored specifically to cultures of each minority. Results suggest that acculturation processes influence tobacco use differentially by gender, and future research is needed to identify the implications of processes in tobacco initiation and cessation.

Adult↗

Bioaccumulation of mercury in muscle tissue of fish in the Elbe River (Czech Republic): multispecies monitoring study 1991-1996.

The study monitored mercury (Hg) contamination of fish muscle tissue at 13 geographical sites that can be regarded as crucial points for an ecotoxicological assessment of the Czech Republic section of the Elbe River. The descriptive part of the study was primarily aimed at comparative evaluation of the Hg load during the period 1991-1996. The conclusions were supported by multivariate statistical analyses of the content of Hg in the muscle tissue of 1251 fish belonging to 23 species with four dominant indicator species: Perca fluviatilis (n=163), Abramis brama (n=173), Rutilus rutilus (n=148), and Leuciscus cephalus (n=166). Considering data from 3- to 5-year-old fish, significantly increased contamination was detected in typical predators compared to the other fish species in all sites (P<0.001). On the other hand, omnivorous and planctivorous species were ranked as the least sensitive for Hg pollution. Perch appeared to be the most contaminated species in the sample with muscle Hg concentration in the range of 0.840-1.398 mg Hg kg(-1). Although less contaminated than perch, muscle contamination of bream sensitively separated differently contaminated sites; the highest load ranged from 0.368 to 0.543 mg Hg kg(-1). Time-related comparison of sampling campaigns revealed no significant trend changes, in either sediment samples or fish tissue. Thus, the analyses documented an evidently rather stabilized total Hg pollution in the Elbe River environment. Multivariate multispecies analyses found the age of analyzed individuals and the feeding strategy of a given species as the most important, however mutually interactive, covariates for Hg accumulation in muscle tissue. The analyses revealed decreasing sensitivity of older predator individuals to differentiate highly and moderately contaminated sites. Benthophagous species mostly kept their discrimination capacity toward contaminated sites in all age categories, with the exception of bream that was rather linked to the pattern typical for predator species. The unclear position of omnivorous species, represented namely by roach, corresponded with their weak bioindicator power, mainly in the young age categories.

Animals↗

Plasma levels of procalcitonin and neopterin in multiple trauma patients with or without brain injury.

Clinical and experimental evidence suggests that traumatic brain injury (TBI) leads to a systemic immune response. To examine whether TBI causes a release of procalcitonin (PCT) or neopterin (NT) into the circulation, we compared plasmatic mediator levels among multiple injured patients with or without TBI. In total, 98 trauma patients (24 with TBI only, 39 with extracranial injuries excluding TBI, and 35 with combined injuries) and 35 healthy volunteers were studied. Blood was sampled at 15 predefined time points within 132 h after injury and analysed for NT and PCT. Multivariate statistical comparisons were adjusted for different severity of head, thorax, abdomen and extremity injuries, as quantified by the Abbreviated Injury Scale (AIS). PCT was normal 3 h after trauma, but 24 h after extracranial injuries a massive release (median 3 ng/mL) was observed. Significant positive associations between injury severity and posttraumatic PCT levels were found for abdominal and extremity, but not for cranial or thoracic injuries. Only modest changes of marginal statistical significance were detected for NT. The maximum increase per AIS point was 9% (95% confidence intervals [CI]: 3-16%). The effect of TBI on NT release was significant only at 108 h posttrauma with a 5% (95% CI: 1-10%) increase per AIS point. TBI induces a release of PCT and NT into the plasma, but this effect seems to be smaller for intra- than for extracranial injuries, probably due to more extensive surgery for abdominal and extremity injuries.

Adult↗

[An analysis of the prognostic factors in renal-cell carcinoma].

OBJECTIVES: The study proposes the analysis of the influence of gross, microscopical and clinical pathoanatomical prognostic factors in the survival of patients with RCC through univariance and multivariance statistical analysis, and its global evaluation as a predictive model. PATIENTS AND METHOD: The study involved 218 RCC cases operated on over 20 years, with a mean follow-up of 60 months. RESULTS AND CONCLUSIONS: All prognostic factors studied have a significant influence on the survival. When studied jointly, they include separately and in order of significance the metastatic involvement, mitotic index, cava vein involvement, nuclear grade and sarcomatoid histologic pattern. Also, we confirm that considered jointly they conform a valid predictive model.

Carcinoma, Renal Cell↗