Biomedical subjects

W Vach

Publications and source records attributed to W Vach.

At least 19 recordsLinked to original sources

PubMed2005

Efficacy of A-line AEP Monitor as a tool for predicting acceptable tracheal intubation conditions during sevoflurane anaesthesia.

BACKGROUND: It is essential for the clinical anaesthetist to know whether patients are sufficiently anaesthetized to tolerate direct laryngoscopy and endotracheal intubation. Because of the lack of an accurate objective method to determine the level of general anaesthesia, under- or overdosing of anaesthetics may occur. Auditory evoked potential (AEP) is one of several physiological parameters under investigation. We aimed to determine the clinically required depth of anaesthesia, measured by the A-line AEP Monitor and expressed as A-Line ARX Index (AAI) for 90% probability of acceptable conditions for endotracheal intubation. METHODS: We studied 108 patients anaesthetized by mask with increasing concentration of sevoflurane in 30% oxygen and 70% nitrous oxide. Fentanyl 1.5 microg kg(-1) and glycopyrrolate 0.2 mg were administered intravenously immediately before starting induction of anaesthesia. The monitor was programmed to give an alarm at AAI 10, 15, 20, 25 or 30 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was registered and endotracheal intubation was attempted. Intubation conditions were assessed by an observer blinded to the AAI. RESULTS: At AAI 10 we found acceptable conditions in 91% (confidence interval [CI 72-99%]) of patients. The prediction probability value P(K) of AAI was 0.69 (CI 0.59-0.79) and the P(K) of end-expiratory sevoflurane concentration was 0.93 (CI 0.87-0.99). ED(90) (the AAI with a 90% probability of acceptable intubation conditions) was calculated as 8.5 (CI 0-17.5). CONCLUSIONS: AAI indicates the depth of anaesthesia necessary for acceptable endotracheal intubation conditions. Under the conditions of the present study, end-expiratory sevoflurane concentration was a better predictor and may turn out to be more useful in the clinical setting.

Adult↗

PubMed2005

Haplotype effects on human survival: logistic regression models applied to unphased genotype data.

Haplotype based linkage disequilibrium (LD) mapping exhibits higher power than the single locus approach because it makes use of the LD information contained in the flanking markers. New statistical methods have been proposed to help to infer haplotype effects on human diseases using multi-locus genotype data collected from unrelated individuals. In this paper, we introduce a statistical procedure for measuring haplotype effects on human survival using the popular logistic regression model with haplotype based parameterizations. By modeling haplotype frequency as a function of age, our model infers haplotype effects by estimating and testing the slope parameters under different genetic mechanisms (multiplicative, dominant, or recessive). In addition, by estimating the sex-specific slope parameters, our model allows the detection of sex-specific haplotype effects or haplotype-sex interactions. As an example, we apply our model to an empirical dataset on a stress related gene, interleukin-6, to look for haplotypes that affect individual survival and for haplotype-sex interactions. We show that our logistic regression based haplotype model can be a helpful tool for researchers interested in the genetics of human aging and longevity.

Female↗

PubMed2005

A comparison between criteria for diagnosing atopic eczema in infants.

BACKGROUND: Epidemiological studies have shown different estimates of the frequency of atopic eczema (AE) in children. This may be explained by several factors including variations in the definition of AE, study design, age of study group, and the possibility of a changed perception of atopic diseases. The role of IgE sensitization in AE is a matter of debate. OBJECTIVES: To determine the prevalence and cumulative incidence of AE in a group of unselected infants followed prospectively from birth to 18 months of age using different diagnostic criteria; to evaluate the agreement between criteria; and to describe the association between atopic heredity and postnatal sensitization, respectively, and the development of AE according to the different diagnostic criteria. METHODS: During a 1-year period a consecutive series of 1095 newborns and their parents were approached at the maternity ward at the Odense University Hospital, Denmark and a cohort of 562 newborns was established. Infants were examined and followed prospectively from birth and at 3, 6, 9, 12 and 18 months of age. AE was diagnosed using four different criteria, the Hanifin and Rajka criteria, the Schultz-Larsen criteria, the Danish Allergy Research Centre (DARC) criteria developed for this study and doctor-diagnosed visible eczema with typical morphology and atopic distribution. Additionally, the U.K. diagnostic criteria based on a questionnaire were used at 1 year of age. Agreement between the four criteria was analysed at each time point and over time, and agreement between the four criteria and the U.K. questionnaire criteria was analysed. RESULTS: The cumulative 1-year prevalence of AE using the Hanifin and Rajka criteria was 9.8% (95% confidence interval, CI 7-13%), for the Schultz-Larsen criteria it was 7.5% (95% CI 5-10%), for the DARC criteria 8.2% (95% CI 6-11%), for visible eczema 12.2% (95% CI 9-16%) and for the U.K. criteria 7.5% (95% CI 5-10%). The pairwise agreement between criteria showed good agreement, with rates varying between 93% and 97% and kappa scores between 0.6 and 0.8. Agreement analysis of diagnoses between the four criteria demonstrated that cumulative incidences showed better agreement than point prevalence values. CONCLUSIONS: Agreement between different criteria for diagnosing AE was acceptable, but the mild cases constituted a diagnostic problem, although they were in the minority. Repeated examinations gave better agreement between diagnostic criteria than just one examination. Atopic heredity was less predictive for AE than sensitization to common food and inhalant allergens in early childhood.

Adolescent↗

PubMed2004

Socio-economic inequalities in first-time use of antidepressants: a population-based study.

OBJECTIVE: To analyse whether first-time use of antidepressants (incidence) and selection of TCAs (tricyclic antidepressants) versus new-generation drugs are associated with socio-economic status and psychiatric history. METHOD: We conducted a population-based cohort study using registry data covering Funen County, Denmark. A total of 305,953 adult residents without antidepressant prescriptions 5 years prior to the study period (1998) were included. RESULTS: The 1-year incidence rate of antidepressant prescription (1.7%) increased with age. It was higher in people who were female, less educated, unemployed, those receiving old-age or disability pension, low-income groups, and singles. The proportion prescribed new-generation antidepressants (82%) showed no difference according to socio-economic variables (education, annual income and socio-economic group), but was higher among the young and single. Admission to psychiatric hospital within 4 years prior to the study period was associated with high-incidence rate of antidepressant prescription and overall a preference for the new-generation antidepressants. CONCLUSION: Socio-economic status did not seem to influence the selection of TCAs versus new-generation antidepressants. Compatible with the general epidemiology of depression, low socio-economic status was associated with a high number of first-time users of antidepressants in the population, and the incidence rate increased with age.

Adolescent↗

PubMed2004

Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs.

This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently developed statistical model for measuring marker-longevity associations [Yashin et al., 1999: Am J Hum Genet 65:1178-1193], enabling direct power comparison between linkage and association approaches. The non-parametric linkage (NPL) scores estimated in the region harboring the causal allele are evaluated to assess the statistical power for different genetic (allele frequency and risk) and heterogeneity parameters under various sampling schemes (age-cut and sample size). Based on the genotype-specific survival function, we derived a heritability calculation as an overall measurement for the effect of causal genes with different parameter settings so that the power can be compared for different modes (dominant, recessive) of inheritance. Our results show that the ASP approach is a powerful tool in mapping very strong effect genes, both dominant and recessive. To map a rare dominant genetic variation that reduces hazard of death by half, a large sample (above 600 pairs) with at least one extremely long-lived (over age 99) sib in each pair is needed. Again, with large sample size and high age cut-off, the method is able to localize recessive genes with relatively small effects, but the power is very limited in case of a dominant effect. Although the power issue may depend heavily on the true genetic nature in maintaining survival, our study suggests that results from small-scale sib-pair investigations should be referred with caution, given the complexity of human longevity.

Age Factors↗

PubMed2004

Assessing genetic association with human survival at multi-allelic loci.

Genetic variation plays an important role in natural selection and population evolution. However, it also presents geneticists interested in aging research with problems in data analysis because of the large number of alleles and their various modes of action. Recently, a new statistical method based on survival analysis (the relative risk model or the RR model) has been introduced to assess gene-longevity associations [Yashin et al. (1999) Am J Hum Genet 65: 1178-1193] which outperforms the traditional gene frequency method. Here we extend the model to deal with polymorphic genes or gene markers. Assuming the Hardy-Weinberg equilibrium at birth, we first introduce an allele-based parameterization on gene frequency which helps to cut down the number of frequency parameters to be estimated. We then propose both the genotype and allele-based parameterizations on risk parameters to estimate genotype and allelic relative risks (the GRR and ARR models). While the GRR model allows us to investigate whether the alleles are recessive, dominant or codominant, the ARR model further minimizes the number of parameters to be estimated. As an example, we apply the methods to empirical data on Renin gene polymorphism and longevity. We show that our models can serve as useful tools in searching for important genetic variations implicated in human aging and longevity.

Aging↗

PubMed2004

Efficacy of the A-line AEP monitor as a tool for predicting successful insertion of a laryngeal mask during sevoflurane anesthesia.

BACKGROUND: The use of clinical signs for assessing depth of anesthesia is unreliable during periods with little noxious stimulation. A patient may appear adequately anesthetized at one moment at a given level of stimulation, but may later, when facing other more intense stimuli, show signs of insufficient anesthesia. In order to prevent under- or overdosing of anesthetics, an anesthesia depth monitor that is able to predict responses to noxious stimulation would therefore be useful. Auditory evoked potentials (AEP) is one of several physiological parameters under investigation. The method has been improved by rapid extraction and conversion of the AEP curve into an index (A-Line ARX Index = AAI). We aimed to determine the clinically required depth of anesthesia, measured by the A-line AEP Monitor, for at least 90% probability of acceptable insertion conditions for a laryngeal mask airway (LMA). METHODS: We studied 112 patients anesthetized by mask with increasing concentration of sevoflurane in oxygen. The monitor was programmed to give an alarm at AAI between 15 and 40 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was recorded and the LMA inserted. Insertion conditions were assessed by an observer blinded to the AAI. RESULTS: The ED(95) and prediction probability (P(K)) for AAI were 14.5 (CI 7.4-21.6) and 0.76 (0.66-0.86), respectively, while the ED(95) and P(K) for expiratory sevoflurane concentration were 4.36% (CI 3.73-4.98) and 0.95 (0.91-0.99). CONCLUSIONS: AAI indicates the level of depth of anesthesia necessary for acceptable laryngeal mask insertion conditions. End-expiratory sevoflurane concentration was the better predictor.

Adult↗

PubMed2004

Reactivity to patch tests with nickel sulfate and fragrance mix in infants.

The pattern of patch test reactivity to nickel sulfate and fragrance mix was studied with respect to patch test performance, reproducibility and clinical relevance in a population of unselected infants followed prospectively from birth to 18 months of age. TRUE Testtrade mark patches with nickel sulfate in 3 concentrations, 200, 66 and 22 microg/cm(2), and fragrance mix 430 microg/cm(2) were used. A likely case of nickel sensitivity was defined as a reproducible positive reaction with at least homogeneous erythema and palpable infiltration occurring at least 2x and present at both the 12 and 18 months follow-up. 543 infants (268 girls and 275 boys) were tested at least 1x, 304 were tested at both 12 and 18 months. The prevalence of a reproducible positive reaction to nickel was 8.6% (20 girls and 6 boys). A transient positive reaction was observed in 111 children. Clinical relevance of nickel sensitivity was found in only 1 child. No reproducible positive reaction to fragrance mix was found. The high proportion of transient patch test reactivity to nickel sulfate 200 microg/cm(2) indicates that this standard concentration used for adults cannot be applied to infants. The interpretation of a single positive nickel patch test in infants must be assessed with caution and it is probably of non-specific or irritant nature.

Allergens↗

PubMed2004

Microvessel density compared with the Chalkley count in a prognostic study of angiogenesis in breast cancer patients.

AIMS: Evaluation of angiogenesis by intratumoral vessel profiles can be performed by different methods. The aim of this study was to investigate the prognostic value of estimates obtained by the intratumoral microvessel density (MVD) method and then to compare with corresponding estimates obtained by the Chalkley method. METHODS AND RESULTS: A total of 330 patients treated for primary, unilateral, invasive breast carcinoma were included. The median follow-up time was 14 years and 4 months. The microvessels were immunohistochemically stained by antibodies to CD34. MVD was not significantly correlated with any clinicopathological variables. By univariate analysis, MVD showed no prognostic value with regard to recurrence-free survival (RFS) or overall survival (OS), while the Chalkley count had significant prognostic value (P < 0.0001; RFS and OS). In the Cox multivariate analysis, MVD had no prognostic impact [median HR [confidence interval (CI)] was 0.93 [0.66, 1.32] for RFS; and HR [CI] was 0.86 [0.62, 1.19] for OS], while the Chalkley count [median HR (CI) was 2.12 (1.48, 3.06) for RFS; and HR (CI) was 1.71 (1.23, 2.37) for OS] provided independent prognostic value when adjusted for age, menopausal status, axillary lymph node status, tumour size, histological grade, adjuvant systemic treatment and radiation therapy. In comparing the results obtained by MVD in our study with those from other published studies we find good agreement. CONCLUSIONS: The Chalkley count technique seems to be preferable for estimating angiogenesis with regard to the prognostic stratification of breast cancer patients, based on its strong prognostic impact, and acceptable reproducibility.

Age Distribution↗

PubMed2004

Appendicectomy has no beneficial effect on admission rates in patients with ulcerative colitis.

BACKGROUND AND AIMS: Those who have had an appendicectomy have a reduced risk of developing ulcerative colitis. However, the effect of appendicectomy on disease activity in patients with ulcerative colitis has not been established. METHODS: We used the Danish National Patient Registry to identify all incident cases of ulcerative colitis in Denmark during the period 1981 to 1999. Of these, 202 had an appendicectomy after their first admission with ulcerative colitis. In these patients, we compared the incidence rate of hospitalisations with ulcerative colitis as first diagnosis during the period between the onset of ulcerative colitis and appendicectomy, with the rate of such hospitalisations after appendicectomy. To adjust for the clinical course of ulcerative colitis unrelated to appendicectomy, we extracted a reference cohort (n = 808), matched to the index subjects with respect to age, sex, and year of first admission, but with an intact appendix. RESULTS: The rate of admission with ulcerative colitis as first diagnosis decreased by 47% after appendicectomy (rate ratio 0.53 (95% confidence interval (CI) 0.36-0.80)). However, the reference cohort showed a similar decline in admission rate (rate ratio 0.51). Thus appendicectomy had no apparent beneficial effect on admission rate after adjustment for the clinical course of disease unrelated to appendicectomy (adjusted rate ratio 1.05 (95% CI 0.67-1.67)). CONCLUSIONS: Appendicectomy had no significant beneficial effect on admission rates in patients with ulcerative colitis.

Adult↗

PubMed2003

GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?

We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non-diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we investigate the association of GLUT4 expression with the intracellular triglyceride (TG) content in the same muscle fibres and with plasma lipid parameters. We used histochemistry and stereology to study the relationship between TG content and GLUT4 expression in muscle fibres from obese, obese type 2 diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (p<0.05). We found an increased TG density in slow twitch fibres of obese diabetic subjects compared to obese (p<0.05) and lean controls (p<0.008). Intracellular TG densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced GLUT4 expression. The GLUT4 expression was not associated with an increased intracellular triglyceride content or with increased plasma FFA levels. Thus, intracellular TG content and circulating FFA may not influence glucose transport directly through GLUT4 expression.

Adult↗

PubMed2003

Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity.

In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture the age-dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age-dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important gene variations that contribute to human aging and longevity.

Age Factors↗

PubMed2002

GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres.

In this study we examined the relationship between GLUT4 expression at the plasma membrane and muscle fibre size in fibre-typed human muscle fibres by immunocytochemistry and morphometry in order to gain further insight into the regulation of GLUT4 expression. At the site of the plasma membrane, GLUT4 was more abundantly expressed in slow as compared to fast fibres at the same fibre diameter (p < 0.01) and the GLUT4 expression increased with increasing fibre radius independently of fibre type (p < 0.01). The GLUT4 density at the surface of slow fibres of both diabetic and obese was reduced compared to control subjects at the same diameter (p < 0.001). Fast fibres in obese and type 2 diabetic subjects expressed a fibre-volume-dependent GLUT4 expression (p < 0.001), while this did not reach significance in slow fibres (obese p = 0.18 and diabetic p = 0.06). Our results show that increasing fibre volume is associated with increasing GLUT4 expression in both slow and fast fibres. Based on the possible dependency of GLUT4 expression on volume, we hypothesize that the reduced GLUT4 expression in obesity and type 2 diabetes may partly be compensated for by physical activity.

Adult↗

PubMed2001

A logistic regression model for measuring gene-longevity associations.

The logistic regression model is a popular model for data analysis in epidemiological research. In this paper, we use this model to analyze genetic data collected from gene-longevity association studies. This new approach models the probability of observing one genotype as a function of the age of investigated individuals. Applying the model to genotype data on the TH and 3'ApoB-VNTR loci collected from an Italian centenarian study, we show how it can be used to model the different ways that genes affect survival, including sex- and age-specific influences. We highlight the advantages of this application over other available models. The application of the model to empirical data indicates that it is an efficient and easily applicable approach for determining the influences of genes on human longevity.

Adolescent↗

PubMed2000

On the misuses of artificial neural networks for prognostic and diagnostic classification in oncology.

The application of artificial neural networks (ANNs) for prognostic and diagnostic classification in clinical medicine has become very popular. In particular, feed-forward neural networks have been used extensively, often accompanied by exaggerated statements of their potential. In this paper, the essentials of feed-forward neural networks and their statistical counterparts (that is, logistic regression models) are reviewed. We point out that the uncritical use of ANNs may lead to serious problems, such as the fitting of implausible functions to describe the probability of class membership and the underestimation of misclassification probabilities. In applications of ANNs to survival data, further difficulties arise. Finally, the results of a search in the medical literature from 1991 to 1995 on applications of ANNs in oncology and some important common mistakes are reported. It is concluded that there is no evidence so far that application of ANNs represents real progress in the field of diagnosis and prognosis in oncology.

Decision Support Techniques↗

PubMed2000

Vascular grading of angiogenesis: prognostic significance in breast cancer.

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P < 0.0001), node-negative patients (P < 0.0001) and node-positive patients (P < 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P < 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer.

Adult↗

PubMed2000

Immunohistochemical assessment of oestrogen and progesterone receptors: correlations with the DCC method and clinical outcome in primary breast cancer patients.

Two different methods to determine steroid receptors were analysed with respect to their ability to estimate prognosis in primary breast cancer patients. The immunohistochemical assay (IHA) was compared with the dextran-coated charcoal (DCC) method of receptor determination. A random sample of 281 patients with invasive ductal carcinoma was drawn from 841 consecutive patients with primary breast carcinoma treated at Odense University Hospital between 1 January 1980 and 31 December 1990. Receptor determination by the DCC method had been carried out previously in 164 patients for the oestrogen receptor and in 132 patients for the progesterone receptor. The former group was reassessed by IHA with the antibody ER1D5, and the latter with the antibody PgR-ICA. The median follow-up time was 8.3 years (range 2.9-12.9 years). A cutoff of zero was used for the DCC method. Immunohistochemical results were quantified by counting in systematically random sampled fields of vision and values above zero were considered to be positive. Overall agreement of positive and negative cases was 86% for the oestrogen receptor and 83% for the progesterone receptor. Although the study included a limited number of patients, receptor positive cases fared better than negative cases in all situations. Investigation of the prognostic power revealed that classification based on IHA allowed better discrimination of patients than classification based on the DCC method. The reason for this difference might be because distinction between benign and malignant tissue is possible using the IHAmethod. Thus, IHAresults appear to be more clinically relevant.

Journal Article↗

PubMed2000

The prognostic value of angiogenesis by Chalkley counting in a confirmatory study design on 836 breast cancer patients.

This study addresses the prognostic value of estimating angiogenesis by Chalkley counting in breast cancer. A population-based group consisting of 836 patients with operated primary, unilateral invasive breast carcinomas was included from a predefined region and period of time. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. The Chalkley count was obtained by a 25-point grid within three, subjectively selected, vascular tumor areas of highest microvessel density. The Chalkley count was analyzed in three categories using predefined Chalkley cutoff points at five and seven. There were significant correlations between high Chalkley counts and axillary lymph node metastasis, large tumor size, high histological malignancy grade, and histological type. A high Chalkley count showed lower probabilities of recurrence-free survival (P < 0.0001) and overall survival (P < 0.0001). In the Cox multivariate analysis, the hazard ratio (and 95% confidence interval) showed that the increased risk to die were: 1.55 (1.19-2.03) with Chalkley counts between 5 and 7; 2.26 (1.72-2.98) with counts > or =7 compared with counts < or =5; and 1.46 (1.14-1.87) with counts > or =7 compared with counts between 5-7. The study confirmed that estimation of angiogenesis by Chalkley counting had independent prognostic value in breast cancer patients. The Chalkley count could be useful to stratify node-negative patients for adjuvant treatment.

Adenocarcinoma↗