[Peripheral hearing disorders in childhood. Results of an evidenced based consensus conference].
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Biomedical subjects
Publications and source records attributed to W Reuter.
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UNLABELLED: The treatment of rhinosinusitis seen in the light of uncertain pathogenesis and variable symptoms is under discussion and ranges from the administration of antibiotics, decongestants and anti-allergic agents to no treatment. In this randomized, prospective, double-blind and controlled study the effect of a 14-day treatment (1-2 sprays into each nostril t.d.) with either isotonic Ems Mineral Salts (EMS) solution (Siemens & Co., Bad Ems, Germany) or xylometazoline solution (0.05%) was tested in children (n=66) aged 2-6 years. MAIN OUTCOMES: the degree of mucosal inflammation, nasal patency, general state of health, condition of the middle ear, auditory function as well as an assessment of complaints by the parents. With the exception of the hearing defects, all parameters showed a clear improvement in both treatment groups at the end of the observation period (p>0.001). The hearing defects showed only a trend towards improvement. At the end of the study no differences between the treatment groups could be determined. However, at the intermediate examination after the first 7 days of treatment more favourable results were seen in the group treated with EMS. No undesired medicinal effects were observed, although in 7 out of 34 cases the nasal spray was improperly used in the group treated with xylometazoline. The results of the study show that there is no difference in efficacy between an exclusive treatment by EMS solution in children aged 2-6 years and a treatment with xylometazoline, but with the distinction that with EMS the length of use was not restricted, there were not the potential side effects of nasal decongestants, and there was no contraindication in the newborn and infants.
BACKGROUND: It remains controversial whether fatty acid (FA) composition of breast milk relates to development of atopy in the infant. This study evaluates FA in colostrum from mothers of children at high risk of atopy in association with atopy at the age of 1 year. METHODS: The FA of colostrum were analyzed for 218 children (60 with low birth weight between 1500 and 2500 g, 84 with a history of maternal atopy, and 74 with an elevated cord blood immunoglobulin (Ig)E of >0.9 IU/ml). Total lipids were extracted, methylated and separated by gas-liquid chromatography. Laboratory screening for allergic sensitization and clinical examination took place within the Leipzig Allergy Risk Children's Study (LARS). RESULTS: Low birth weight was correlated with low percentage levels of 20:2n-6, 22:2n-6, and 22:3n-3 (r = 0.14, P < 0.05; r = 0.14, P < 0.05 and r = 0.20, P < 0.01, respectively) and low gestational age at birth was correlated with low 22:3n-3 (r = 0.15, P < 0.05). There was no association between FA and atopic eczema at the age of 1 year. However, high linoleic acid (LA, 18:2n-6) was linked to high specific IgE against cow's milk protein (P < 0.05), and low docosapentaenoic acid (DPA, 22:5n-3) was associated with elevated total serum IgE (P < 0.05) at the age of 1 year, respectively. CONCLUSIONS: The polyunsaturated fatty acid composition of colostrum in a high risk newborn population shows associations with atopic sensitization at the age of 1 year and may be predictive for later atopic disease.
OBJECTIVES AND METHODS: Several studies showed the efficacy of inpatient geriatric treatment. Different outcomes were reported for geriatric patients treated in outpatient facilities. To analyze the course of rehabilitation, 312 patients (62.2% female) with a mean age of 77.2 years (SD = 7.4) in a geriatric day hospital were evaluated regarding a) changes of functional deficits and mobility, b) cognitive function and c) depression. Patients were examined with a geriatric assessment including activities of daily living, Tinetti, Timed-up and go, Mini Mental State Examination (MMSE), Clock Completion Test, Handgrip Strength-Test, Money-Counting Test and Geriatric Depression Scale (GDS) at admission and discharge. RESULTS: All examined parameters had changed significantly after treatment. A clear decrease in the portion of patients with disability-related outcomes in the examined parameters (Barthel Index, Tinetti, Timed-up and go, MMSE, GDS) was demonstrated: a) the proportion of patients with a Barthel Index under 75 had decreased by 26.5%, the proportion of patients with an increased risk of falls was reduced by 27%, b) the proportion of patients with a MMSE Score less than 24 was decreased by 14.8% and c) mild effects were achieved in depression. CONCLUSIONS: Day hospital geriatric treatment leads to an improvement of functional deficits, mobility and mental health of patients. The results contrast to other studies in day hospital treatment.
The laboratory analyses of 404 participants of the health study GUNDULA, 201 men and 203 women between 30 and 80 years old, were performed to evaluate the variables for the determination of biological age. From the more than 70 laboratory variables resulting from clinical-chemical and hematologic tests and from urinalysis, less than 40 are significantly age-dependent. About half of these variables were examined by regression analysis to evaluate whether they are useful for the estimation of biological age by a laboratory index. Considerable sex differences were observed. The laboratory indexes for the participants altogether (resulting from 13 parameters) and separated for women (10 parameters) and men (8 parameters) show more variations than the biological age estimated by non-invasive parameters. In men only, there exists a significant but inverse correlation between laboratory index and relative aging rate, the difference between biological and chronological age. The results of some striking variables (e.g. dehydroepiandrosterone sulfate and others) and the results of an explorative factor analysis with regard to possible interconnections between variables and chronological age will be discussed.
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LDL apheresis is highly efficient in reducing elevated plasma cholesterol. Due to strict indications only patients with severe, refractory hypercholesterolemia are treated with this method. Mutations in the LDL receptor gene are major genetic causes for severe hypercholesterolemia. Screening the entire gene in LDL apheresis patients from Saxony should determine whether an increased frequency of defined mutations is responsible for the atherogenic hypercholesterolemia in this group. 31 unrelated patients (15 male, 16 female, age 33-71 yrs.) were included in the analysis. The LDL-R gene was screened using SSCP and/or automated sequencing. The familial defective apolipoprotein B-100 (FDB) mutation was genotyped using established PCR techniques. Nineteen of 31 patients were carriers of an LDL-R mutation. Ten missense and two nonsense mutations, three insertions and two deletions were detected. The mutations C74S, C74R, T87M, 660delC, 662insCCCCG, 680insGGACAAATCTGA, 1428insC and 2167delG have not been previously described. One patient was compound heterozygous for two missense mutations. Two further patients were heterozygous for FDB. No mutations were found among controls. A genetic background for hypercholesterolemia in the LDL-R could be established in about 61% of the patients examined. Therefore, methods of DNA analysis allow to recognize and adequately treat a large portion of high-risk individuals at an early stage.
OBJECTIVES: Upregulation of leukocyte adhesion molecules under atherogenic conditions is accompanied by the release of soluble forms of adhesion molecules into the bloodstream. Vegetarians have a favorable cardiovascular risk profile. The aim of the present study was to assess the levels of circulating E-selectin (cE-selectin), circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular adhesion molecule-1 (cVCAM-1) in both vegetarians and subjects of the average population and furthermore to evaluate the age dependence of cell adhesion molecules. METHODS: 24 male and 59 female vegetarians (mainly members of the German Society of Vegetarians) and 124 male and 179 female control subjects (volunteers, of the ILSE study Leipzig = Interdisciplinary Long Time Study of Health Adult Age and the Lipid-Study Leipzig), 18-89 years old were included in the study. The serum levels of circulating cell adhesion molecules were determined using monoclonal antibody-based ELISA assays (R & D Systems, Abingdon, Europe Ltd.). RESULTS: Vegetarians were characterized by a favorable lipid profile and a low prevalence of common risk factors for atherosclerosis. This group showed a tendency towards lower cICAM-1 levels in comparison with control subjects. Furthermore, significantly lower cE-selectin levels were found in the group of vegetarians. An age-dependent increase of cVCAM-1 and cICAM-1 levels was found both in the group of vegetarians and control subjects. No significant differences were noted regarding the gender of the subjects included in the study. CONCLUSION: Low cE-selectin levels of vegetarians may reflect the favorable cardiovascular risk profile of this group. Furthermore, the present data indicate that cVCAM-1 and cICAM-1 are age-dependent parameters independent of risk for atherosclerosis.
Recently, two isoforms of the growth hormone-binding protein (GHBP), which is identical with the extracellular domain of the growth hormone receptor (GHR), have been described. One isoform contains the exon 3 (E3+GHBP) and one excludes the exon 3 (E3-GHBP). The distribution of both isoforms in peripheral blood and their functional relevance is so far unknown. To study the molecular distribution of both species we have analysed sera of 141 subjects with average weight, overweight and obesity by newly developed immunoassays. The relationship between the different molecular forms of GHBP and specific parameters of body composition as well as risk factors of metabolic disturbances, were then examined. The extracellular domain of the exon 3-retaining and -deleted isoforms of the GHR are released as E3+GHBP and E3-GHBP into the peripheral circulation. Furthermore, both molecular species do not show any correlation to each other (r = 0.67) and their relative proportion in blood is gender-dependent with a higher E3-GHBP proportion in females (P < 0.01). E3+GHBP appears to have a considerably stronger correlation to indicators (BMI, fat mass, waist circumference) and metabolic risk factors (fasting insulin, uric acid, triglycerides, apolipoprotein B, diastolic blood pressure) of adiposity than E3-GHBP, indicating differences in their functional significance. The availability of assays for the determination of GHBP isoforms may be very important for the study of the GH receptor and its soluble extracellular domain, GHBP.
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Cytochrome c6from the unicellular green alga Scenedesmus obliquus was sequenced, crystallized in its reduced and oxidized state and the three-dimensional structure of the protein in both redox states was determined by X-ray crystallography. Reduced cytochrome c6crystallized as a monomer in the space group P 21212, whereas the oxidized protein crystallized as a dimer in the space group P 3121. The structures were solved by molecular replacement and refined to 1. 9 and 2.0 A, respectively. Comparison of the structures of both redox states revealed only slight differences on the protein surface, whereas a distortion along the axis between the heme iron and its coordinating Met61 residue was observed. No redox-dependent movement of internal water molecules could be detected. The high degree of similarity of the surfaces and charge distributions of both redox states, as well as the dimerization of cytochrome c6as observed in the oxidized crystal, is discussed with respect to its biological relevance and its implications for the reaction mechanisms between cytochrome c6and its redox partners. The dimer of oxidized cytochrome c6may represent a molecular structure occurring in a binary complex with cytochrome b6f. This assembly might be required for the correct orientation of cytochrome c6with respect to its redox partner cytochrome b6f, facilitating the electron transfer within the complex. If the dimerization is not redox-dependent in vivo, the almost identical surfaces of both redox states do not support a long range differentiation between reduced and oxidized cyt c6, i.e. a random collision model for the formation of an electron transfer complex must be assumed.
An electrophoretically purified allophycocyanin-linker complex, AP. LC7.8, from phycobilisomes of Mastigocladus laminosus has been crystallized in the orthorhombic space group P212121. Cryocrystallographic x-ray measurements enabled the structural analysis of the complex at a resolution of 2.2 A. The asymmetric unit contains two side-to-side associated "trimeric" (alphabeta)3 allophycocyanin complexes comprising the linker polypeptide in a defined orientation inside the trimer. The linker representing a protein fold related to the prosegment of procarboxypeptidase A is in contact with only two of the three beta-subunits and directly interacts with the corresponding chromophores of these proteins. In addition to a modulation of the chromophores' spectral properties, the linker polypeptide attracts the alphabeta-subcomplexes, thereby bringing the beta-chromophores closer together. These results will enable interpretations of energy-transfer mechanisms within phycobiliproteins.
BACKGROUND: Glutathione S-transferases (GSTs) are detoxification enzymes, found in all aerobic organisms, which catalyse the conjugation of glutathione with a wide range of hydrophobic electrophilic substrates, thereby protecting the cell from serious damage caused by electrophilic compounds. GSTs are classified into five distinct classes (alpha, mu, pi, sigma and theta) by their substrate specificity and primary structure. Human GSTs are of interest because tumour cells show increased levels of expression of single classes of GSTs, which leads to drug resistance. Structural differences between classes of GST can therefore be utilised to develop new anti-cancer drugs. Many mutational and structural studies have been carried out on the mu and alpha classes of GST to elucidate the reaction mechanism, whereas knowledge about the pi class is still limited. RESULTS: We have solved the structures of the pi class GST hP1-1 in complex with its substrate, glutathione, a transition-state complex, the Meisenheimer complex, and an inhibitor, S-(rho-bromobenzyl)-glutathione, and refined them to resolutions of 1.8 A, 2.0 A and 1.9 A, respectively. All ligand molecules are well-defined in the electron density. In all three structures, an additionally bound N-morpholino-ethansulfonic acid molecule from the buffer solution was found. CONCLUSIONS: In the structure of the GST-glutathione complex, two conserved water molecules are observed, one of which hydrogen bonds directly to the sulphur atom of glutathione and the other forms hydrogen bonds with residues around the glutathione-binding site. These water molecules are absent from the structure of the Meisenheimer complex bound to GST, implicating that deprotonation of the cysteine occurs during formation of the ternary complex which involves expulsion of the inner bound water molecule. The comparison of our structures with known mu class GST structures show differences in the location of the electrophile-binding site (H-site), explaining the different substrate specificities of the two classes. Fluorescence measurements are in agreement with the position of the N-morpholino-ethansulfonic acid, close to Trp28, identifying a possible ligandin-substrate binding site.
Since reliable headphones are now available, clinical audiometry can also be performed in extended high frequencies (EHF). Hearing in frequencies over 10 kHz is more influenced by age, noise and toxicity. Thus it is useful to take additionally results in children to establish the normal hearing threshold. In the present study, 35 pre-school children (ages 4-7 years) were tested by EHF (8 kHz-16 kHz) using a new Sennheiser HDA-200 headphone. The hearing thresholds recorded corresponded to those of other studied. Median and standard deviations for 10 kHz were 25 dB(SPL) +/- 12 dB(SPL), 35 dB(SPL) +/- 12 dB(SPL) for 12.5 kHz and 50 dB(SPL) +/- 15 dB(SPL) for 16 kHz. In the older children (> 5 years), hearing thresholds could be more reliably determined and were 10 dB(SPL) better than in the younger children (< 5 years). Thresholds at 10 kHz-12.5 kHz corresponded to those found in adults, but were more sensitive by 5 dB(SPL)-15 dB(SPL) in the 14 kHz-16 kHz range.
BACKGROUND: Elevated Lp(a) levels are known as risk factor for premature coronary artery disease and apoplexy. To our knowledge ophthalmologic alterations have not been described in combination with elevated Lp(a) levels. We examined whether patients with LP (a) elevation had an increased incidence of keratoconjunctivitis sicca. PATIENTS AND METHODS: 27 patients, 16 women and 11 men were examined. The Lp(a) value was in all patients definitively pathological. The following examinations were performed: history, slitlamp examination, Schirmer-test, impressioncytology, fluorescein staining of the cornea, applanation tonometry and examination of the ocular fundus. RESULTS: The results show a pathologic Schirmer-test in 70.3% of the eyes, in 81.5% a pathologic impressioncytology, and in 48.1% a pathologic fluorescein staining. The Schirmer-test is not sufficiently sensitive and specific in diagnosing the dry eye, whereas impression cytology is highly sensitive and specific. CONCLUSIONS: We could show, that in more than 80% of the examined patients at least one sign of keratoconjunctivitis sicca was found; however we did not find a correlation between the height of the Lp(a) level and the degree of pathologic impression cytology. Further examinations are needed to investigate the causal connection between keratoconjunctivitis sicca and Lp(a) elevation.
The oxidative modification of LDL could play an important role for the development of atherosclerosis. The present study was undertaken to compare the concentration of vitamin E in serum and lipoproteins between patients with coronary heart disease and a healthy control group. The study included 36 male patients with angiographically established coronary three-vessel disease and 32 healthy volunteers. Cholesterin, triglyceride, LDL-cholesterin, HDL-cholesterin, and vitamin E in serum and in lipoproteins were determined. The serum vitamin E concentration in the patients group was significantly higher than in controls. However, vitamin E was correlated with cholesterin in both groups. The distribution of vitamin E in healthy volunteers was LDL 53%, HDL 34% and VLDL 13%, whereas that in patients was LDL 57%, HDL 26% and VLDL 16%. The level of vitamin E in LDL was in the patient group significantly higher and correlated with the vitamin E- and the cholesterin-concentration in serum. The ratio vitamin E/cholesterin in LDL was in patients discretely lower, whereas the same ratio in HDL was higher. The results suggest that also in patients with coronary artery disease vitamin E is related to the lipid concentration. The decreased ratio vitamin E/cholesterin in LDL could be attributed to the oxidative modification of LDL.
In 56 patients with HLP (40 with hypertriglyceridemia and mixed HLP respectively and 16 with hypercholesterolemia), changes in the lipid state and in the parameters of the antioxidative potential before and after a 4-week olive-oil phase, and after 8-, 20- and 32-week intakes of salmon-oil capsules were determined. The treatment with salmon-oil led to a decrease of triglycerides in patients with hypertriglyceridemia and mixed HLP respectively, on the other hand, it led to an increase of cholesterol in hypercholesterolemia. The increase of malondialdehyde as measure of lipid peroxidation in both patient groups underlines the necessity of a substitution of antioxidants. Further investigations are necessary before wide use of fish-oil capsules can be recommended, especially to avoid side-effects.