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Pneumococcal bacteremia in adults over a 10-year period at University Hospital, Leiden.

The medical records on all cases of pneumococcal bacteremia in adults at the University Hospital, Leiden, over a 10-year period (1976-1986) were retrospectively reviewed. In this series of 147 episodes (an annual incidence of 0.8 episodes/10,000 adults), overall mortality was 25.9%. Factors significantly related to a higher mortality rate were shock, respiratory insufficiency, preexisting renal failure, and rapidly fatal underlying disease. Several laboratory abnormalities-such as a low percentage of band forms, an elevated level of serum lactate dehydrogenase, and hyperbilirubinemia-were significantly related to a poor outcome. Multilobar pneumonia and meningitis were both associated with high mortality, although not to a statistically significant degree. Discriminant analysis showed the presence of shock as the most powerful predictive factor of death. Surprisingly, prior splenectomy did not correlate with higher mortality. Treatment with beta-lactam antibiotics favorably influenced the outcome of illness in patients with ultimately fatal and nonfatal underlying disease, while the use of these agents in patients with rapidly fatal underlying disease did not correlate significantly with a good prognosis.

Adolescent↗

Calculation with MCNP of capture photon flux in VVER-1000 experimental reactor.

The aim of this study is to obtain by Monte Carlo method the high energy photon flux due to neutron capture in the internals and vessel layers of the experimental reactor LR-0 located in REZ, Czech Republic, and loaded with VVER-1000 fuel. The calclated neutron, photon and photon to neutron flux ratio are compared with experimental measurements performed with a multi-parameter stilbene detector. The results show clear underestimation of photon flux in downcomer and some overestimation at vessel surface and 1/4 thickness but a good fitting for deeper points in vessel.

Computer Simulation↗

Transforming growth factor-beta 1 (TGF-beta 1) expression in normal healthy pulps and in those with irreversible pulpitis.

AIM: To evaluate the Transforming Growth Factor-beta 1 (TGF-beta 1) expression in normal healthy pulps and in those with irreversible pulpitis. METHODOLOGY: Twenty-three normal, healthy pulps were removed from mandibular third molars, and 20 pulps were retrieved from teeth with irreversible pulpitis. TGF-beta 1 was evaluated in the odontoblastic and subodontoblastic layers, in the stromal cells (fibroblasts), and in the blood vessels. TGF-beta 1 expression was determined by evaluating 500 cells in the odontoblastic and subodontoblastic layers and 500 fibroblasts in the stroma for each specimen, and counting the number of positive cells. The number of the positive vessels was evaluated in 10 high power fields (HPF). In almost all cases, the cellular positivity was cytoplasmatic. Statistical analysis was performed using Mann-Whitney U- and Student's t-tests. RESULTS: A higher expression of TGF-beta 1 was found in the odontoblastic-subodontoblastic layer of the irreversible pulpitis specimens; this difference was statistically significant (P = 0.0002). No statistically significant difference was observed between the two groups in TGF-beta 1 expression in the stromal cells (P = 0.54) or in the vascular component (P = 0.94). CONCLUSIONS: The higher and statistically significant expression of TGF-beta 1 found in the odontoblastic-subodontoblastic layer of irreversible pulpitis specimens may indicate a role for TGF-beta 1 in the dentinal repair processes after pulp inflammation.

Adolescent↗

Relationship between periodontal disease status and combination of biochemical assays of gingival crevicular fluid.

BACKGROUND: Currently, no biochemical assay involving gingival crevicular fluid is utilized routinely as a screening test for periodontal disease. OBJECTIVE: The objective of the present study was to evaluate the potential of gingival crevicular fluid assay as a screening methodology. METHODS: The subject population was comprised of 27 volunteers. Nine participants were classified as 'subject with periodontal destruction' (SPD) exhibiting at least one site with pocket depth and attachment loss>3.5 mm, whereas the remaining individuals were categorized as 'subject with minimal periodontal destruction' (SMD). Gingival crevicular fluid was collected from fixed sites via a standardized method. Biochemical assays of 12 substances (hemoglobin, albumin, transferrin, alpha(1)-antitrypsin, fibronectin, IgA, IgG, IgM, lactoferrin, myeloperoxidase and neutrophil elastase) were conducted at a commercial laboratory. Power transformation of total quantities in gingival crevicular fluid was performed for statistical analysis. RESULTS: Relationships between total quantity of each substance and periodontal disease status were unclear. Logistic regression analysis yielded six predictive models, which consisted of substance pairs: neutrophil elastase/IgA, neutrophil elastase/hemoglobin, neutrophil elastase/alpha(1)-antitrypsin and neutrophil elastase/IgG, and IgA/albumin and IgA/transferrin (p<0.05). Regression lines for SPD and SMD on a scattergram of IgA and neutrophil elastase were nearly parallel within the range of amounts in gingival crevicular fluid. The predictive model derived from both substances afforded sensitivity and specificity of 88% and 94%, respectively. CONCLUSIONS: These results indicated that the combination of IgA and neutrophil elastase in gingival crevicular fluid may be crucial for prediction of periodontal disease status. Furthermore, these data suggested that biochemical assays employing both substances in gingival crevicular fluid may provide a satisfactory screening test for periodontal disease.

Adult↗

Effects of hypocarbia on the pharmacodynamics of sufentanil in humans.

Descriptors of power and frequency derived from power spectral analysis of the electroencephalogram (EEG) were used to determine the effects of low-dose sufentanil (0.1 micrograms/kg) on brain activity. The effects of hypocarbia alone and of hypocarbia with sufentanil in patients receiving a N2/O2 (70%:30%) anesthetic were also studied. Hypocarbia alone caused changes in most EEG descriptors from both the anterior (F3-C3) and posterior (P3-O1) EEG montages. All EEG descriptors in both hypocarbic and normocarbic patients significantly changed when sufentanil was administered, reflecting a shift of power into the lower frequency ranges. When the anterior EEG montages from the two groups that received sufentanil were compared, the delta power band, spectral edge 50 (median power frequency), and the relative power in the delta power band divided by the alpha plus beta power bands [D/(A + B)] in the hypocarbic group exhibited a significantly greater shift of power into the lower frequency range. It is concluded that (a) power spectral analysis is a sensitive measure of the effects of hypocarbia and small doses of sufentanil on the brain; (b) the power spectral analysis descriptors--delta power band, spectral edge 50, and [D/(A + B)]--are statistically the most sensitive to EEG changes induced by sufentanil; and (c) hypocarbia intensifies patient EEG response to sufentanil, as judged by changes in EEG descriptors.

Adult↗

Distinction between homozygous and heterozygous subjects with hereditary haemochromatosis using iron status markers and receiver operating characteristic (ROC) analysis.

The purpose of the present study was: 1) to evaluate which of the four iron status markers (serum iron, serum transferrin, serum transferrin saturation, serum ferritin) displayed the highest discriminatory potential in the distinction between homozygous patients with hereditary haemochromatosis and heterozygous relatives, 2) to suggest optimum cut-off values for these iron status markers, and 3) to demonstrate how these cut-off values change if the expected utility from a correct diagnosis is incorporated into the analysis. The patients and relatives were found by a nation-wide epidemiological survey. The study population consisted of 162 patients with clinically overt hereditary haemochromatosis and 84 asymptomatic heterozygous relatives. The statistical evaluation was performed using receiver operating characteristic (ROC) curve analysis. The diagnostic power of the iron markers is expressed as the area under the ROC curve. The optimum cut-off value is at the point where the slope of the ROC curve is equal to one. Changes in the optimum cut-off value at varying expected utility from a correct classification was estimated by changing the scaling of the ROC diagram. Serum iron and serum transferrin had the smallest area under the ROC curve, and were both unsuitable as discriminators. Near complete discrimination was obtained with serum transferrin saturation and serum ferritin concentrations, displaying the largest area under the ROC curve (0.991 and 0.998). The optimum threshold value for transferrin saturation was 61%, and for serum ferritin concentration 800 micrograms/l. The transferrin saturation level reflects the presence of the haemochromatosis allele, whereas the serum ferritin concentration indicates the degree of iron overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vivo toxicity screening programs using metabonomics.

Metabonomics is an emerging technology that enables rapid in vivo screening for toxicity, disease state, or drug efficacy. The technology combines the power of high-resolution nuclear magnetic resonance (NMR) techniques with statistical data analysis methods to rapidly evaluate the metabolic "status" of an animal. Complimentary to other profiling technologies like proteomics and genomics, metabonomics provides a fingerprint of the small-molecules contained in a given biofluid through the time course of a study. This article reviews the steps in implementing a metabonomics-based screening program from study design through data analysis. While metabonomics is still a relatively new technology in comparison to the other "omics", published results from metabonomics studies demonstrate its potential impact in the drug discovery process by enabling the incorporation of safety endpoints much earlier in the drug discovery process, reducing the likelihood (and cost) of later stage attrition.

Algorithms↗

Diffuse nodular lung disease on chest radiographs: a pilot study of characterization by fractal dimension.

OBJECTIVE: We present a computer-aided diagnostic technique for identifying nodular interstitial lung disease on chest radiographs. The fractal dimension was used as a numerical measure of image texture on digital chest radiographs to distinguish patients with normal lung from those with a diffuse nodular interstitial abnormality. MATERIALS AND METHODS: Twenty digitized chest radiographs were classified as normal (n = 10) or as containing diffuse nodular abnormality (n = 10) on the basis of readings assigned according to the classification of the International Labour Organization. Regions of interest (ROIs) measuring 1.28 cm2 were selected from the intercostal spaces of these radiographs. The fractal dimension of these ROIs was estimated by power spectrum analysis. The cases were not subtle. RESULTS: The fractal dimension provided statistically significant discrimination between normal parenchyma and nodular interstitial lung disease. The area under the receiver operating characteristic curve was 0.90 (+/- 0.02). One operating point provides sensitivity of 88% with a specificity of 80%. CONCLUSION: The fractal dimension can provide a measure of lung parenchymal texture and shows promise as an element of computer-aided diagnosis, characterization, and follow-up of interstitial lung disease.

Fractals↗

Theoretical structure of adolescent alienation: a multigroup confirmatory factor analysis.

This study examined the construct validity of adolescent alienation using second-order confirmatory factor analysis of the five dimensions conceptualized by Seeman (1959). Analysis was based on data from 275 high school students aged 14 to 18. The hypothesized multidimensionality of the construct was confirmed for both boys and girls using a second-order factor labeled alienation. Central dimensions of alienation as a latent construct were self-estrangement and powerlessness. Social isolation, meaninglessness, and especially normlessness were poorly explained by the second-order factor, suggesting that these dimensions entail enough specificity to be considered separately. A different theoretical model relating these dimensions is suggested and discussed.

Adolescent↗

[Study of genetic polymorphism of 6 short tandem repeat loci in Nongqu Mongolian of inner Mongolia Autonomous Region in China].

OBJECTIVE: To get the genotype and allele frequency distribution of 6 short tandem repeat (STR) loci VWA, FGA, PENTAE, D6S1043, D2S1772, D7S3048 in NongQu Mongolia of China. METHODS: Two hundred and ninety-three unrelated individuals from Nongqu Mongolian were investigated. Polymerase chain reaction and polyacrylamide gel electrophoresis were used. RESULTS: Eighty alleles and 335 genotypes were detected, with frequencies ranging from 0.0017 to 0.2828. All the 6 loci met Hardy-Weinberg equilibrium. The statistical analysis of 6 STR loci showed the heterozygosity (H) >/= 0.7945, the discrimination power (DP) >/= 0.9160, the probability of paternity exclusion (PPE) >/= 0.5919, and the polymorphic information content (PIC) >/= 0.7617. CONCLUSION: These results could serve as valuable data to enrich the Chinese genetic database and play an important role in Chinese population genetic forensic medical application.

Alleles↗

[MELD score in prediction of early mortality in patients suffering refractory ascites treated by TIPS].

UNLABELLED: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is now well established in the treatment of complications of symptomatic portal hypertension such as acute or recurrent variceal bleeding, refractory ascites and Budd-Chiari syndrome. In some patients with refractory ascites who belong to group C according to Child-Pugh classification (score around 12), the indication of the procedure could be very questionable and early mortality is quite high. However, in some cases, the subgroup of such risky patients can profit from TIPS. Child-Pugh classification is used for the stratification of the patients routinely. During the last decade other scoring systems occured to bring a better prognostic value. MELD (Model for End stage Liver Disease) score, based only on laboratory values is one of them. Comparison of these two scoring systems in patients treated by TIPS in previous trials brought certain discrepancy, but MELD score seems to be better in predicting early mortality. The aim of our study was to determine retrospectively the predictive accuracy of MELD score for the early mortality in comparison to Child-Pugh score in patients treated for refractory ascites by TIPS. METHODS: We evaluated 110 patients (mean age 55 years) with liver cirrhosis (61% of patients with alcoholic etiology), who underwent TIPS for refractory ascites in our center from September 1992 to December 2003. MELD and Child-Pugh score was calculated and then compared between groups with early (one month), three month and one year mortality, and those who survived over this period (one, three and twelve months), comparing MELD and Child-Pugh score (ROC analysis and Student's T test were used). RESULTS: Mean follow up was 23 months. Average MELD score in the whole group was (16). In patients, who died within one month the score before TIPS was 21, three months 20 and 18 one year. Comparing MELD score between subgroups and then Child-Pugh score, only for MELD score there was a statistically significant difference (p < 0.05) in one month. Using ROC (AUC) analysis, discriminant power of MELD score was superior to Child-Pugh score for one (0.73 vs 0.63) and three month (0.73 vs 0.67) mortality. The discriminant power for one year mortality was low in both scores. CONCLUSION: MELD scoring system is a better tool to predict the risk of early mortality in patients with refractory ascites treated by TIPS than Child-Pugh classification. The discriminant power was low in both scores in one year horizon.

Ascites↗

[Bamifylline in the therapy of asthmatic syndromes. Efficacy and side effects vs delayed-action theophylline anhydride].

Two homogeneous groups of 8 patients suffering from bronchial asthma or chronic obstructive bronchial pneumonia were treated with slow release theophylline anhydride or bamiphylline respectively, both products being given orally twice a day. The results showed that both drugs possess a powerful bronchodilatory action and therefore have a beneficial effect on subjective symptoms. Statistical analysis confirmed the absence of any significant difference between the two xanthine derivatives, both of which were well-tolerated though bamiphylline offered a slight advantage in this respect. In fact there were no side effects at all in the bamiphylline group whereas there was one case of moderate gastric intolerance in the group given theophylline anhydride, though it was not severe enough to warrant suspension of the treatment or reduction of the dose.

Administration, Oral↗

Evaluation problems of a long-term study on evolving pulmonary arterial hypertension in chronic non specific lung disease.

After having collected a sufficient number of standardized data checked for reliability from patients with chronic non specific lung disease, the following subgroups of pulmonary arterial mean pressure were defined: A = PAP less than 2.7 kPa [= 20 mmHg]; B = 2.7 less than PAP less than 4 kPa; C = PAP greater than 4 kPa [= 30 mmHg]. Within these subgroups a diagnostic classification was also carried out: chronic obstructive lung disease, thrombo-embolic lung disease, diffuse interstitial lung disease. The aims of data processing were: clustering correctly individual cases in one of the I-II-III subgroups based on non-invasive variables only; To define equations predictive of quantitative values of pulmonary arterial mean pressure from non-invasive data; To find regularity of evolution of elevated pulmonary arterial mean pressure in chronic non specific lung disease and detect risk factors and/or beneficial interventions if such exist at all. Two different statistical methods were applied: conditional probability (Bayes theorem) and discriminant analysis. The predictive power of each depends mainly on the seriousness of signs and symptoms denoted by the medical user. Three probability-functions have been defined between severity of single variables and their specificity, sensitivity and probability of pulmonary hypertension. By application of these functions the user can select different quantitative values of variables which determine the proportion of false/true, positive/negative cases. After having chosen the desired values of these proportions, multivariate equations are defined by stepwise regression analysis optimized for predictive power.(ABSTRACT TRUNCATED AT 250 WORDS)

Bayes Theorem↗

A genetic association study of the mu opioid receptor and severe opioid dependence.

OBJECTIVES: Twin, family and adoption studies have suggested that vulnerability to opioid dependence may be a partially inherited trait (Cadoret et al., 1986; Merikangas et al., 1998; Tsuang et al., 1998, 2001). Studies using animal models also support a role for genetic factors in opioid dependence, and point to a locus of major effect on mouse chromosome 10 (Berrettini et al., 1994; Alexander et al., 1996), which harbors the mu opioid receptor gene (Mor1) (Kozak et al., 1994). The gene encoding the human mu opioid receptor (OPRM1) is thus an obvious candidate gene for contributing to opioid dependence. A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence. METHODS: In the current study, we genotyped 213 subjects with severe opioid dependence (89 African-Americans, 124 European-Americans) and 196 carefully screened "supercontrol" subjects (96 African-Americans, 100 European-Americans) at five SNPs residing in the OPRM1 gene. The polymorphisms include three in the promoter region (T-1793A, -1699T insertion and A-1320G) and two in exon 1 (C+17T [Ala6Val] and A+118G [Asp40Asn]). RESULTS: Statistical analysis of the allele frequency differences between opioid-dependent and control subjects for each of the polymorphisms studied yielded P values in the range of 0.444-1.000. Haplotype analysis failed to identify any specific combination of SNPs associated with the phenotype. CONCLUSIONS: Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans.

Base Sequence↗

A comment on confusion in open-field studies: abuse of null-hypothesis significance test.

The confusion in open-field studies which has resulted from a misinterpretation of statistical results was examined. Several discrepant results obtained on the basis of significance tests have revealed that the discrepancy was not so serious as had been thought. Examples of highly reliable but substantially small experimental effects were presented to indicate the erroneous impression given. The expectation that consistent results can always be obtained from even a small sample size was criticized. In order to reduce some of this confusion, the use of strength of association (eta2) together with consideration for statistical power in the interpretation of open-field results was recommended.

Analysis of Variance↗

Pathologic N1 non-small cell lung cancer: correlation between pattern of lymphatic spread and prognosis.

OBJECTIVES: Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survivals. Prognosis and pattern of recurrence seem to be particularly affected by the level of lymph node involvement. METHODS: From 1990 to 1995, a total of 1954 consecutive patients underwent surgical resection for non-small cell lung cancer: 549 (28%) had ipsilateral pulmonary lymph node metastases (N1). The hospital survivors (n = 535) were reviewed. Three levels of lymph node metastases (hilar, interlobar, and lobar) were identified according to the new Regional Lymph Node Classification for Lung Cancer Staging and differentiated from lymph node involvement on the basis of direct invasion. RESULTS: 1 The overall 5-year survival of patients with N1 disease was 40%. Survival was related in the univariate analysis to T classification, level-type of N1 involvement, number of involved nodes, multilevel involvement, Karnofsky Index, R status, and adjuvant therapy. In the multivariate analysis, only T classification and level-type of N1 involvement clearly showed statistical power (P =.000 and P =.001, respectively). The pattern of cancer relapse according to level-type of N1 involvement differed significantly: hilar N1 disease recurred at distant sites in 41% of patients and locoregionally in 12% of patients, whereas N1 disease by direct invasion occurred in 24% and 17% of patients, respectively (P =.030). CONCLUSIONS: Metastases to ipsilateral hilar, interlobar, or both, lymph nodes are associated with a poorer prognosis compared with metastases in intralobar lymph nodes or with lymph node involvement by means of direct invasion. Although surgical resection remains the mainstay of treatment, the high rate of tumor recurrence in both groups mandates further randomized studies with multimodality therapy approaches.

Adult↗

Do nurses exercise power in basic care situations?

Power is a matter of authority and control. It can be wielded either consciously or unconsciously, and it can be either overt or latent. Using a structured questionnaire, this study set out to describe nurses' opinions about the exercise of power in basic care situations in both acute and long-term care. The questionnaire was organized into four categories in which items concerned: power in obligatory daily activities; power in activities necessitated by obligatory activities; power in voluntary activities; and power in activities that take into account the patient's characteristics. The samples consisted of 228 nurses from five medical and surgical wards of district hospitals, and 233 nurses from five geriatric units of a community health centre and from one nursing home in Finland. The final response rate was 65% (acute care 76%; long-term care 55%). Data analysis was based on statistical methods. The results showed that, in the nurses' own opinion, negative power is exercised only in certain situations and in the patient's best interest, when for instance there are concerns that something may happen to the patient.

Adult↗

Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior.

Suicidal behavior, which ranks among the top 10 causes of death worldwide, is an important public-health problem and a psychiatric disorder, which has been the subject of considerable study. Studies have shown association between the serotonin transporter (5-HTT) gene and suicidal behavior, although a proportion of alternative studies have produced contrary results both in terms of positive and negative findings, possibly reflecting inadequate statistical power and the use of different populations. Using the cumulative data from recent years in both European and, more particularly, Asian populations, this updated meta-analysis seeks to examine whether the aggregate data provide evidence of statistical significance, and to clarify the contradictory findings suggested by previous studies. It covers all published studies using multiple research methods up to January 2006. Compared with a previous meta-analysis, which found no association between the 5-HTTLPR polymorphism and suicidal behavior (P=0.38), the current results (39 studies) suggest a significant association with a P-value of 0.0068 (overall odds ratio=0.88 (0.8,0.97)), and supports the involvement of the brain 5-HTT in the pathogenesis of suicidal behavior.

Depressive Disorder↗