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Biomedical subjects

A Manz

Publications and source records attributed to A Manz.

At least 37 records · Page 2Linked to original sources

Inhibitory control in children with traumatic brain injury (TBI) and children with attention deficit/hyperactivity disorder (ADHD).

The behavioural and cognitive sequelae of traumatic brain injury (TBI) have features in common with attention deficit/hyperactivity disorder (ADHD), best characterized by deficits in response inhibition.The performance was, therefore, examined of 27 children with TBI, 31 children with developmental ADHD, and 26 matched controls aged 8-12, on two inhibition tasks: the Stop-Signal Task and a Delayed-Response-Task. Children with TBI and children with ADHD showed a pervasive deficit in their inhibitory control processes with respect to inhibition of both pre-potent and on-going responses. In addition, children with TBI were found to suffer from a general slowing of their information processing, which was not correlated with the inhibition deficit. TBI children with and without a secondary ADHD differed only tendentially in their Mean Go-Reaction time in the stop-task. However, subdividing TBI children according to actigraph data into hypo-, hyper- and normokinetic subgroups revealed that the hyperactive TBI children had inhibitory deficit patterns that were similar to children with developmental ADHD. It is concluded that slowing of information processing speed seems to be a general consequence of TBI in childhood, whereas slowing of the stop-processes or inhibitory deficits, specifically, are associated with post-injury hypo- or hyperactivity.

Attention Deficit Disorder with Hyperactivity↗

[Splenic rupture as a complication of ventilation in the prone position and pneumococcal sepsis as a late complication].

We are reporting the case of a female patient who had to undergo splenectomy after she suffered splenic rupture as a result from "kinetic therapy" during the treatment for pulmonary failure secondary to sepsis. Four years later the patient was again admitted with a clinical picture consistent with sepsis. Two blood cultures were positive for pneumococci confirming the diagnosis of pneumococcal sepsis. This paper discusses the potential risks of kinetic therapy in patients with ARDS. After splenectomy there is increased risk of infection with certain bacteria, funghi, viruses and protozoa. The most common bacterial pathogen is pneumococcus. A polyvalent vaccine is available for prophylaxis. Although penicillin G is still commonly used as an antibiotic therapy for pneumococcal infection, increased resistance of pathogens to penicillin must be anticipated. Alternative antibiotic regimens are demonstrated.

Female↗

[Significance of the label "risk duplication" in occupational medicine expert opinion and redefinition of occupational diseases].

Referring to scientifically well-founded epidemiological statistical parameters for characterising probabilities of causal relationships, a critical assessment is given of the use of the parameter 'doubling risk' in research and expert evidence in occupational medicine. When assessing single cases, the attainment of this frequency level can serve as an appropriate additional argument for assuming a corresponding relationship; but even if lower frequency levels are attained, such a relationship cannot be excluded. In addition to the statistical data, any conspicuous features from the occupational history and from the course of the disease must be included in the analysis. In the investigation of causal relationships, the exclusive consideration of research results with enhanced frequencies dose to the doubling risk value would imply an illegitimate neglect of existing important information and would thus possibly lead to a misjudgement of the real situation. In the author's opinion, this would also result in set-backs both in legislation concerning occupational diseases and in the realm of labour protection.

Germany↗

Chemical amplification: continuous-flow PCR on a chip.

A micromachined chemical amplifier was successfully used to perform the polymerase chain reaction (PCR) in continuous flow at high speed. The device is analogous to an electronic amplifier and relies on the movement of sample through thermostated temperature zones on a glass microchip. Input and output of material (DNA) is continuous, and amplification is independent of input concentration. A 20-cycle PCR amplification of a 176-base pair fragment from the DNA gyrase gene of Neisseria gonorrhoeae was performed at various flow rates, resulting in total reaction times of 90 seconds to 18.7 minutes.

DNA Topoisomerases, Type II↗

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗

Immune cell functions in industrial workers after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: dissociation of antigen-specific T-cell responses in cultures of diluted whole blood and of isolated peripheral blood mononuclear cells.

A comparative analysis was performed of the phenotype and function of peripheral blood leukocytes of two age-matched cohorts of industrial workers in chemical plants, one of which was exposed occupationally to high concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Median actual TCDD burdens were 116 ng/kg and 4 ng/kg, respectively. The phenotype analysis of peripheral blood mononuclear cells (PBMC) revealed no significant differences in the proportions of CD3, CD4, or CD8+ T lymphocytes, of CD16+ natural killer cells, and of CD19+ B lymphocytes. However, in PBMC of the TCDD-exposed workers; the proportion of CD8+ memory T cells (CD45R0+) was significantly higher, and that of lymphocytes with naive phenotype (CD45RA+) was significantly lower than in PBMC of the control group. Polyclonal and antigen-specific T-cell activation was assessed in parallel in isolated PBMC as well as in diluted whole blood cultures. In both culture systems the polyclonally stimulated cytokine release did not differ significantly between the two cohorts; however, we found a significantly reduced interferon gamma release in diluted whole blood cultures but not in isolated PBMC cultures of the TCDD-exposed cohort when we performed an antigen-specific T-cell stimulation with tetanus-toxoid. Therefore, we propose that exposure of individuals to high doses of TCDD can partially impair in the "blood milieu" those T-cell/monocyte interactions that are essential for antigen-specific T-cell responses, whereas isolated PBMC of the same donors appear functionally less affected.

Adult↗

Developments in technology and applications of microsystems.

In the past year, microchips as applied to miniaturised total analysis systems, or microTAS, have benefited from technological improvements in their fabrication and been applied to analysis in many different biological areas. From a technological perspective, salient work includes fast, cheap and easy micromachining in polymers and integrated optical detection. From the bioapplications perspective, advances in DNA and protein separations, cell manipulations, immunoassays and polymerase chain reaction using on-chip electrophoretic separation stand out.

Chemistry Techniques, Analytical↗

Elimination of beta-hexachlorocyclohexane in occupationally exposed persons.

The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of beta-HCH. The data support the assumption of first-order kinetics.

Adipose Tissue↗

Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors.

A prototype miniaturized Total Chemical Analysis System (muTAS) has been developed and applied to on-line monitoring of glucose and lactate in the core blood of anaesthetized dogs. The system consists of a highly efficient microdialysis sampling interface sited in a small-scale extracorporeal shunt circuit ('MiniShunt'), a silicon machined microflow manifold and integrated biosensor array for glucose and lactate detection with associated computer software for analytical process control. During in-vivo testing the device allowed real-time on-screen monitoring of glucose and lactate with system response times of less than 5 min, made possible by the small dead volume of the microflow system. On-line glucose and lactate measurements were made in the basal state as well as during intravenous infusion of glucose or lactate. The prototype muTAS is currently suitable for trend monitoring but refinements are necessary before application of the system for determination of individual lactate values.

Animals↗

Micellar electrokinetic chromatography separations and analyses of biological samples on a cyclic planar microstructure.

Micellar electrokinetic capillary chromatography (MECC) separations and analyses of biological samples on a planar glass microchip capillary electrophoresis device with laser-induced fluorescence solute detection are discussed. A cyclic channel system which permits dead volume free repeated column switching and thus the use of various channel lengths together with a relatively low applied separation voltage is described. It features an unbiased, dead volume free electrokinetic sample inlet system of approximately 12 pL. Because of the small cross section and favorable heat dissipation in glass microstructures, MECC separations with an electric field strength of up to 2000 V/cm achieving efficiencies of submicrometer plate heights can be performed. After a separation length of 2 cm, six fluorescein isothiocyanate labeled amino acids are shown to be separable within a few seconds and with an imprecision for peak areas (or heights) and detection times of < 2% and < 0.5%, respectively. Without application of electrokinetic solute stacking, the detection limit of fluorescein isothiocyanate labeled arginine is 3.3 nM, corresponding to approximately 40 zmol injected. Furthermore, the feasibility of directly applying human urine and serum samples onto the uncoated channel system is demonstrated and first data of the successful performance of a chip-based MECC immunoassay for serum theophylline are presented. Compared to MECC in conventional fused-silica capillaries, MECC analyses on microchips can be performed 1-2 orders of magnitude faster, with higher efficiency and at no expense of accuracy and precision. Furthermore, versatility is shown to be much increased with the use of a cyclic rather than a single-path channel system. The MECC separation efficiency of fluorescein isothiocyanate labeled amino acids is shown to be comparable to that obtained by gel electrophoresis performed in the same chip layout.

Amino Acids↗

Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.

In an occupational cohort study, the relation between exposure to phenoxy herbicides, and contaminants (dioxins and furans) and cancer mortality was investigated. A total of 2,479 workers from four plants in Germany were included, with a mortality follow-up until the end of 1989 (for one cohort, until the end of 1992). A total of 484 deaths were recorded yielding a standardized mortality ratio (SMR) of 101 (95 percent confidence interval [CI] = 92-111) for total mortality, and an SMR of 119 (CI = 100-141) for all malignant diseases. A variety of herbicides was produced, including those which are known to have been contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). High dioxin and furan exposure (in particular, exposure to TCDD, but also to higher chlorinated dioxins) had occurred in two of the four plants as shown by blood-fat measurements in a sample of workers. Mortality from all neoplasms increased with latency and was highest in the largest plant where the highest TCDD blood levels were recorded. An increased mortality in the total cohort from respiratory cancer (SMR = 154, CI = 115-202), cancer of the buccal cavity and pharynx (SMR = 295, CI = 135-560), and non-Hodgkin's lymphoma (SMR = 326, CI = 119-710) was observed. Our findings are consistent with results from other cohorts which showed an increased overall cancer mortality and mortality of respiratory cancer after long-term exposure to these phenoxy herbicides and dioxins.

Adipose Tissue↗

Elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in occupationally exposed persons.

The elimination of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was investigated in a group of n = 43 exposed workers with 2 blood measurements and n = 5 workers with 3 measurements. Under the assumption of a one-compartment, first-order kinetic model the median half-life for 2,3,7,8-TCDD was 7.2 yr, while for the other dioxins the estimates were between 3.7 yr for 1,2,3,4,6,7,8-HpCDD (hepta-chlorinated) and 15.7 yr for 1,2,3,7,8-PCDD (penta-chlorinated). For the furans median half-lives between 3.0 yr for 1,2,3,4,6,7,8-HpCDF and 19.6 yr for 2,3,4,7,8-PCDF were observed. There was no indication for a deviation from a first-order kinetic. Increasing age and percent body fat were associated with increasing half-life for most of the congeners. Smokers in general had a faster decay than non- and ex-smokers. In summary, the higher chlorinated PCDD/F like TCDD appear to be highly persistent in humans with half-lives ranging between 4 and 12 yr.

Adipose Tissue↗

Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany.

The relation between mortality (all cause; cancer; cardiovascular diseases (International Classification of Diseases, Ninth Revision (ICD-9), codes 390-459); ischemic heart diseases (ICD-9 codes 410-414)) and exposure to polychlorinated dibenzo-p-dioxins and -furans (PCDD/F) was investigated in a retrospective cohort study. The cohort consisted of 1,189 male workers in a chemical plant in Hamburg, Federal Republic of Germany, who had produced phenoxy herbicides, chlorophenols, and other herbicides and insecticides known to be contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and other, higher chlorinated dioxins and furans. The authors reported previously on cancer mortality in this cohort for the follow-up period 1952-1989. The current study covers the years 1952-1992 and investigates the relation of PCDD/F exposure to mortality using a quantitative estimate of PCDD/F exposure for the whole cohort derived from blood and adipose tissue levels measured in a subgroup (n = 190). Quintiles and deciles of these estimates served as dose parameters in the estimation of relative risks (RRs), using year-of-birth stratified Cox regression. An unexposed cohort of gas workers served as an external reference group. The total mortality was elevated in all dose groups. The highest relative risk was observed for the highest 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decile (RR = 2.43, 95% confidence interval (CI) 1.80 to 3.29). Cancer mortality and mortality due to ischemic heart diseases showed a dose-dependent relation with TCDD and all PCDD/F combined. The highest relative risks for cancer (RR = 3.30, 95% CI 2.05 to 5.31) and ischemic heart diseases (RR = 2.48, 95% CI 1.32 to 4.66) were observed in the highest PCDD/F exposure group. The pattern of effects and tests for trend were similar when the lowest exposure group within the chemical worker cohort served as the reference, but the relative risks were smaller and the confidence intervals were larger. Potential confounding exposures complicate the interpretation of the internal comparison. These findings indicate a strong dose-dependent relation between mortality due to cancer or ischemic heart diseases and exposure to polychlorinated dioxins and furans.

Causality↗