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Biomedical subjects

G Förster

Publications and source records attributed to G Förster.

At least 19 recordsLinked to original sources

Influence of poly(L-lysine) on the structure of dipalmitoylphosphatidylglycerol/water dispersions studied by X-ray scattering.

The interaction between the negatively charged phospholipid DPPG and positively charged poly(L: -lysine) (PLL) of different lengths was studied by X-ray scattering in the SAXS and WAXS region. As a reference pure DPPG (Na salt) was investigated over a wide temperature range (-30 to 70 degrees C). The phase behavior of DPPG in aqueous and in buffer/salt dispersions showed a metastable subgel phase at low temperatures and a recrystallization upon heating before reaching the liquid-crystalline phase. The presence of additional salt stabilizes the bilayer structure and decreases the recrystallization temperature. Large changes in the SAXS region are not connected with changes in chain packing. In DPPG/PLL samples, the PLL is inserted between adjacent headgroup layers and liberates counterions which give rise to a freezing point depression. In the complex with DPPG PLL form an alpha-helical secondary structure at pH 7 and temperatures below the gel to liquid-crystalline phase transition. This prevents DPPG from recrystallization and strongly increases the stacking order. The lamellar repeat distance is decreased and fixed by the helix conformation of PLL in the gel phase. PLL with n = 14 is too short to form helices and is squeezed out reversibly from the interbilayer space upon cooling by freezing of trapped water. In dispersions with longer PLLs (n > 400) at -20 degrees C a 1D crystallization of PLL alpha-helices in the aqueous layer between the headgroups takes place. A structural model is presented for the lateral periodic complex, which is similar to the known cationic lipid/DNA complex.

Colloids↗

[How do pleasant and unpleasant odours change the breathing pattern?].

BACKGROUND: Pleasant odours are thought to stimulate whereas unpleasant odours are thought to shorten it. This common breathing behaviour should be tested with short pure odour stimuli. The question was: Is there an influence on exhalation as well? METHOD: 53 normosmic subjects (33 female, 20 male, mean 22,3 years) had to breathe through one nostril. The other nostril was closed using a foam nose tip with a tube connected to a manometer to record the respiratory pressure. The signal was digitally converted and visualised with LabView-software. Odours were presented in front of the nose with a flow-olfactometer OM 2S by Kobal. Hydrogen sulphide (H2S) as an unpleasant pure odour and phenylethylalcohol (PEA) as a pleasant pure odour were used in weak, moderate and strong concentration. The stimulus duration was 200 ms. The onset of stimulus was triggered manually in late exhalation during regular breathing pattern. The interstimulus interval was at least 3 min. A trial consisted of 16 stimuli (4 weak, 2 moderate, 2 strong of both odours). From the recording the duration and the areas below the respiration curves of inhalation and exhalation were calculated. The changes of these four respiratory parameters were estimated using the ratio of the first breathing cycle after stimulus to the average from the five regular breathing cycles prior to stimulation. Only changes of more than +/- 20 % were defined as an olfactory evoked respiratory response (OERR). RESULTS: Short PEA stimuli evoked about three times more frequently an increase than a decrease of duration of inhalation. The area below the inhalatory curve was enlarged. The subjects inhaled the pleasant odour more deeply and for longer. Short H2S-stimuli evoked three times more frequently a decrease of duration of exhalation than an increase. Due to the forced exhalation an increase of the area below the exhalatory curve was observed in these cases. Changes of inhalation did not show any trend. The subjects exhaled quickly to breathe fresh air in the following cycle. Every subject showed some OERR. 52 subjects responded to both odours. One subject responded to PEA only. The individual frequency of OERRs in a trial ranged from 16 % to 84 %. CONCLUSIONS: In all normosmic subjects some OERRs are evoked by repeated H2S- and PEA-stimuli. Strong stimuli do not increase the rate of OERRs. Therefore, the use of perithreshold stimuli is recommended for respiration-olfactometry.

Adult↗

[Olfactory dysfunction. Epidemiology, pathophsiological classification, diagnosis and therapy].

The present manuscript is the result of a collaborative effort within the framework of the Working Group of Olfactology and Gustology of the German Society for ENT, Head and Neck Surgery. It provides a comprehensive overview about the current views on the epidemiology, terminology, diagnostics, and therapy of olfactory dysfunction, and aims to offer a framework for the standardized procedures for the diagnosis and therapy of olfactory disorders.

Algorithms↗

[Medicolegal screening of olfactory function].

Prior to nose surgery the birhinal ability to smell should be tested routinely. From the medico-legal point of view a short screening-test consisting of 5 or 8 test items is not sufficient. It is recommended to use an identification test with 12 or 16 items. The results of these tests taken together with the patients' self estimation, the patients' history and the rhinoscopic findings offer a satisfactory evaluation of the patients' ability to smell in most cases. In case of discrepancies a more detailed test determining the TDI-value is recommendable. If the 16-identification test is used, it is sufficient to add the values of the threshold and the discrimination measurements with the "Sniffin' Sticks" to complete a full TDI score.

Algorithms↗

[Unusual manifestation of zoster sine herpete as unilateral caudal cranial nerve syndrome].

Multiple lower cranial nerve palsies are a rare complication following varicella zoster virus (VZV) reactivation, especially if typical herpetic eruptions are lacking. We report a case of a 45-year-old, immunocompetent male with unilateral involvement of the cranial nerves VIII, IX, X, and XI without skin lesions. Cerebrospinal fluid (CSF) studies revealed mononuclear pleocytosis with intrathecal antibody synthesis against VZV, while polymerase chain reaction (PCR) did not detect VZV or HSV (herpes simplex virus). The patient almost completely recovered after aciclovir administration. VZV reactivation without rash (zoster sine herpete) may lead to multiple cranial nerve palsies. PCR is a useful tool to detect VZV-DNA in CSF, but negative results do not exclude a reactivation. In case of multiple cranial nerve palsies of unknown etiology with mononuclear pleocytosis in CSF tumors of the skull base, meningitis tuberculosis, and meningeosis have to be excluded, and antiviral therapy should be discussed.

Acyclovir↗

[Polyglandular autoimmune syndrome type II: epidemiology and forms of manifestation].

BACKGROUND AND OBJECTIVE: Polyglandular autoimmune syndrome (PAS), is characterized by the coexistence of several autoimmune diseases, affecting predominantly the endocrine glands. The juvenile form (PAS type I) is distinguished from the adult type II in which autoimmune thyroiditis, adrenal cortical insufficiency and diabetes mellitus type I predominate. The connections between epidemiological, clinical and immunological aspects were analysed and described in this study of patients with PAS type II. PATIENTS AND METHODS: Among a total patient population of over 15,000 seen in our endocrinological university policlinic from 1992 through 1996, the clinical data of all 151 patients with PAS type II were analysed retrospectively. RESULTS: Of the 151 patients with PAS 37 were male (aged 16-74 years, median 42 years) and 114 female (aged 16-84 years; median 46 years), a prevalence of 1:100, 92 patients (61%) had diabetes mellitus type I (78% males, 55% females; p = 0.013), 50 (33%) had hyperthyroidism (32% and 33%; difference not significant), 49 had Hashimoto's thyroiditis (14% and 39%; p = 0.005) and 28 (18.5% had Addison's disease (14% males, 20% females; n.s.). Vitiligo was less common, occurring in 30 (20%), alopecia in 9 (6%), pernicious anaemia in 5 (5%) and hypogonadism in 8 (5%). The most common combination was diabetes type I with thyroiditis (33%), the time between manifestations of each disease being highly variable, diabetes was the first manifestation in half the cases. Partial cell antibodies were present in 62 patients (54%), and 52% had positive thyroid-associated antibodies without manifest signs of thyroid disease. CONCLUSION: PAS occurs relatively often among patients of an endocrinological centre, with a 3:1 female to male ratio. Because there is usually a long interval between the onset of the various endocrine diseases, regular monitoring of patients with an endocrine autoimmune disease is indicated, specific tests to be performed if additional immune diseases are suspected.

Addison Disease↗

[Cost effective planning of controlled trials with diagnostic instruments of limited reproducibility].

This paper proposes a simple approach for sample size prediction in controlled diagnostic or clinical trials for group comparison when the diagnostic (imaging) instrument under consideration shows limited reliability and thus calls for taking replicate measurements on each study subject. Using a specified cost function for the overall trial, a cost optimum replication number per subject is predicted, resulting in a cost-optimum predicted group size. This approach results in remarkable cost-effectiveness, as single assessment costs based on the imaging method under consideration only present a small fraction of the overall costs of preparing study subjects for a series of measurement replications by, for example, injection of nuclear or contrast agents.

Controlled Clinical Trials as Topic↗

Ultrastructural characterization of peptide-induced membrane fusion and peptide self-assembly in the lipid bilayer.

The peptide sequence B18, derived from the membrane-associated sea urchin sperm protein bindin, triggers fusion between lipid vesicles. It exhibits many similarities to viral fusion peptides and may have a corresponding function in fertilization. The lipid-peptide and peptide-peptide interactions of B18 are investigated here at the ultrastructural level by electron microscopy and x-ray diffraction. The histidine-rich peptide is shown to self-associate into two distinctly different supramolecular structures, depending on the presence of Zn(2+), which controls its fusogenic activity. In aqueous buffer the peptide per se assembles into beta-sheet amyloid fibrils, whereas in the presence of Zn(2+) it forms smooth globular clusters. When B18 per se is added to uncharged large unilamellar vesicles, they become visibly disrupted by the fibrils, but no genuine fusion is observed. Only in the presence of Zn(2+) does the peptide induce extensive fusion of vesicles, which is evident from their dramatic increase in size. Besides these morphological changes, we observed distinct fibrillar and particulate structures in the bilayer, which are attributed to B18 in either of its two self-assembled forms. We conclude that membrane fusion involves an alpha-helical peptide conformation, which can oligomerize further in the membrane. The role of Zn(2+) is to promote this local helical structure in B18 and to prevent its inactivation as beta-sheet fibrils.

Amino Acid Sequence↗

Acellular muscle with Schwann-cell implantation: an alternative biologic nerve conduit.

Denatured or acellular muscle grafts are known to support axonal regeneration. With increasing gap length, failure of regeneration is evident, due to the lack of viable Schwann cells in the graft. The authors created a biologic nerve conduit, in a rat sciatic nerve model, by implanting cultured Schwann cells into an acellular gracilis muscle. Autologous nerve grafts and acellular muscle grafts without Schwann cells served as controls. After 6 weeks, regeneration was assessed clinically, histologically, and morphometrically. Polymerase chain reaction (PCR) analysis showed that the implanted Schwann cells remained viable within the graft. Good regeneration was noted in the muscle-Schwann cell group, while regeneration in the muscle grafts without Schwann cells was significantly impaired. The muscle-Schwann cell graft demonstrated systematic and organized regeneration, including the proper orientation of regenerated fibers. The number of axons regenerating through the muscle-Schwann cell grafts was significantly increased, compared with the acellular muscle without Schwann cells. Implantation of Schwann cells into acellular muscle thus provided a biologic conduit with large basal lamina tubes, as a pathway for regenerating axons. The positive effects of Schwann cells, producing neurotrophic and neurotropic factors, supported axonal regeneration.

Animals↗

Increased sulfatation of orbital glycosaminoglycans in Graves' ophthalmopathy.

Accumulation of interstitial glycosaminoglycans (GAG) in orbital tissue of patients with Graves' ophthalmopathy (GO) leads to edema, increased orbital pressure, and proptosis. In this study, a new, highly sensitive, high performance liquid chromatography method was developed to determine the altered concentration and biochemical composition of different GAG polymers in orbital connective tissue of 27 GO patients and 18 controls. GAG were isolated by tissue homogenization and digestion, followed by sequential enzymatic GAG hydrolysis and high performance liquid chromatographic analysis of the resulting alpha,beta-unsaturated disaccharides. High recovery rates of 78 +/- 6% (mean +/- SE) and a detection limit of 4.0 microg/L (0.01 micromol/L) were obtained. Total tissue GAG amounted to 254 +/- 16 microg/g wet tissue wt in patients and 150 +/- 13 microg/g (P < 0.0001) in controls. Regarding the GAG polymers, marked differences were detected between patients and controls (chondroitin sulfate, 127 +/- 13 vs. 47 +/- 5 microg/g; hyaluronic acid, 56 +/- 5 vs. 34 +/- 4 microg/g; both P < 0.0001; dermatan sulfate, 77 +/- 6 vs. 69 +/- 6 microg/g; P < 0.05). In patients, chondroitin sulfate was the major GAG component (48 +/- 6 vs. 31 +/- 5% of total GAG in controls), whereas dermatan sulfate was dominant in controls (46 +/- 8% vs. 30 +/- 5%). The sulfated disaccharide digestion products were markedly increased (P < 0.0001) in patients, and the ratio of sulfated vs. total disaccharide content was 85 +/- 6% vs. 65 +/- 5% (P < 0.05) in patients and controls, respectively. As accumulation of negatively charged sulfate residues in GAG disaccharides results in enhanced water-binding capacity, beside inflammation and increased volume of the orbital adipose tissue, the altered structure and nature of sulfated GAG units in the orbit may be responsible for the pathogenic changes in Graves' ophthalmopathy.

Adult↗

[Bioequivalence of a combination of levothyroxine and iodine in comparison with levothyroxine only. A controlled double-blind study of bioavailability].

BACKGROUND: Iodine deficiency is the main cause of endemic goitre. Iodine supplementation and decrease of pituitary TSH are the therapeutical aims. In this study, bioavailability of levothyroxine combined with iodide and the same dose of levothyroxine alone were compared. PATIENTS AND METHODS: Fourty-eight subjects aged 18 to 40 years were randomly assigned for 6 days either 150 micrograms levothyroxine and 150 micrograms iodide (group A, n = 25) or 150 micrograms levothyroxine (group B, n = 23). Baseline TSH and thyroid hormones were measured 2 days before starting therapy as well as daily till day 6. TRH-test (delta TSH) and thyroid sonography were performed at day -2 and 6. RESULTS: During therapy baseline TSH decreased markedly from 1.26 to 0.35 mU/ml (median) in group A and from 1.37 to 0.39 to 0.39 mU/ml in group B (both p < 0.001), as well as delta TSH (A from 5.66 to 2.61 mU/ml; B from 6.3 to 2.95 mU/ml; p < 0.001). Difference of delta TSH (day -2 versus day 6) was negatively correlated to body surface (r = -0.307; p < 0.05). TT4 levels increased in both groups (A from 7.1 to 9.1 microU/dl; B from 7.2 to 9.4 microU/dl; p < 0.005). No significant differences were noted between both groups for thyroid-related parameters. In both groups, confidence intervals for baseline TSH and TT4 were in the expected range. CONCLUSION: In this study, similar bioavailability and bioequivalence for levothyroxine and the combination of levothyroxine with iodide were demonstrated.

Adolescent↗

[Endocrine orbitopathy 1998].

BACKGROUND: Ophthalmopathy is the most common extrathyroidal manifestation of Graves' disease, also called thyroid-associated ophthalmopathy. CLINICS: This autoimmune disorder is characterized by a lymphocyte infiltration of the retrobulbar space. Activated T cells react with the target organ and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema of the peri- and retrobulbar tissue and enlargement of the extraocular muscles. During the inflammatory stage, the increased orbital pressure results in the clinical manifestation of the eye disease. DIAGNOSIS AND TREATMENT: Thus, therapeutic immunosuppression is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of the thyroid eye disease. In recent years, new pathogenetic aspects and clinical randomized trials led to modified therapy concepts. CONCLUSION: Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with thyroid-associated ophthalmopathy.

Cytokines↗

[Individually dosed levothyroxine with 150 micrograms iodide versus 100 micrograms levothyroxine combined with 100 micrograms iodide. A randomized double-blind trial].

BASIC PROBLEM AND OBJECTIVE: Intrathyroid deficiency and the influence of thyroid stimulating hormone (TSH) are the main pathogenetic factors in the development of endemic euthyroid goitre. Goitre reduction is achieved with either administration of levothyroxine, which diminishes hypophyseal TSG production, or of iodide. Aim of this study was to compare the efficacy of treatment with a dose-fixed combination of levothyroxine plus iodide with that of an individualized dosage of levothyroxine plus iodide. PATIENTS AND METHODS: After randomization 49 patients with euthyroid goitre (24 women, 25 men, aged 20-43 years) were treated for 12 weeks in a double-blind trial. Patients in group A received levothyroxine in a weight-adapted dosage (75,100 or 150 micrograms) plus 150 micrograms iodide, while those in group B were given a fixed dosage of 100 micrograms levothyroxine plus 100 micrograms iodide. Basal TSH, thyroid hormones, iodide excretion, hyperthyroid score and sonographic volume of the thyroid were determined before treatment and after 12 weeks. RESULTS: Basal TSH levels were reduced in both groups (P < 0.0001), without significant difference between the two groups (median relative change: group A 78.1%, group B 52.8%). Thyroid volume was decreased independently of the form of treatment (P < 0.0001) (median relative reduction: group A 37.6%, group B 30.9%; difference not significant). Iodide excretion rose in both groups, without significant difference (group A 107%, group B 49%). There was hardly any change of the hyperthyroid score in both groups. There were no side effects. CONCLUSION: Both forms of medication were equally efficacious and well tolerated in the treatment of euthyroid goitre.

Adult↗

Analysis of orbital T cells in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) has a major effect on the two compartments of the retro-orbital (RO) space, leading to enlargement of the extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue is a characteristic feature of TAO and there is current interest in whether these T cells are specifically and selectively reactive to RO tissue itself. We recently established 18 T cell lines (TCL) from RO adipose/connective tissue of six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T cells reactive to autologous RO tissue protein fractions. Here we report on the phenotype characteristics and cytokine gene expression profiles of these orbital TCL and on their immunoreactivity to the organ-specific thyroid antigens thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG). Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL), interferon-gamma (IFN-gamma) (n = 10), tumour necrosis factor-beta (TNF-beta) (n = 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-alpha (n = 12) and IL-10 (n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other 16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were predominantly CD4+ there were no significant relationships between TCL phenotype, cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare) occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine gene expression in all RO tissue-reactive TCL support the concept that TAO is a tissue-specific autoimmune disease, distinct immunologically from the thyroid, and involving both T cell and B cell autoimmune mechanisms in disease pathogenesis.

Adult↗

Glycosaminoglycans in thyroid eye disease.

Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAG) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with thyroid eye disease (TED). In order to analyze whether the alteration of distribution pattern and biochemical composition of GAG and proteoglycans play a role in the development of the disease, a highly specific high-pressure liquid chromatography (HPLC) method was developed. The concentration of total GAG, chondroitin sulfate A (CA), dermatan sulfate (DS), and hyaluronic acid (HA) was determined in patients and controls, revealing marked differences in urinary concentration of total GAG and HA, as well as an elevation of CA in patients versus controls. Method sensitivity was 0.86 for patients with active disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation. Furthermore, distribution pattern of orbital extracellular matrix GAG exhibited a significant increase in the tissue fractions of CA and HA in patients with TED in comparison to controls. In conclusion, GAG polysaccharides not only play a major role in the pathogenesis of TED but have been successfully introduced as an activity marker of the disease.

Chondroitin Sulfates↗

[Combination therapy of endemic goiter with two different thyroxine/iodine combinations].

AIM: Of this study was to investigate the extent of thyrotropin (TSH) suppression and volume reduction in combination therapy of endemic goitre. We compared an individually adapted dose of thyroxine with a fixed dose. METHODS: 105 patients of a multicenter study (randomised, single blinded, controlled) received daily a weight-adjusted LT4-dose in combination with 150 micrograms iodide (group A) or a fixed combination of 100 micrograms LT4 plus 100 micrograms iodide (group B), respectively. At the beginning and after 12 weeks TSH-levels and goitre volume were examined. RESULTS: Although the amount of thyrotropin suppression showed no differences in both groups, there were more patients in the weight-adjusted treatment group with completely suppressed thyrotropin serum concentrations (p < 0.05). Both groups showed a reduction of goitre volume of 24% CONCLUSION: A weight-adjusted LT4-dose of 1.4 micrograms/kg body weight often leads to subclinical hyperthyroidism. To obtain low TSH-levels without complete suppression LT4-doses of 1.0 microgram/kg body weight plus 150 micrograms iodide are probably sufficient.

Adolescent↗

HPLC glycosaminoglycan analysis in patients with Graves' disease.

1. Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAGs) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with Graves' eye disease. 2. A highly specific method to determine the concentration and biochemical composition of different GAGs was developed in order to obtain a sensitive test system for the activity of the disease. By means of this method, GAG excretion in 24 h urine collections of 56 patients and 21 controls was analysed by precipitation with cetylpyridinium chloride and potassium acetate in ethanol, followed by sequential enzymic hydrolysis with chondroitin AC lyase, chondroitin ABC lyase and hyaluronate lyase, with HPLC analysis of the resulting alpha, beta-unsaturated disaccharides by anion-exchange chromatography. 3. Concentrations of GAG, chondroitin sulphate A (CA), dermatan sulphate (DS) and hyaluronic acid (HA) were determined in patients and controls, with high recovery rates [72.2 +/- 5.3%, mean +/- SEM; detection limit, 4.2 micrograms/l (0.01 mumol/l)], revealing marked differences in urinary concentrations of total GAG and HA, as well as an elevation of CA in patients compared with controls. 4. Method sensitivity was 0.86 for patients with active Graves' eye disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation (before therapy: GAG, 111.49 +/- 40.32; CA, 59.58 +/- 21.34; DS, 25.05 +/- 8.12; HA, 26.88 +/- 11.63 mg/24 h; during therapy: GAG, 54.22 +/- 10.94; CA, 20.52 +/- 4.58; DS, 17.65 +/- 3.46; HA, 16.05 +/- 3.69 mg/24 h), whereas GAG excretion increased markedly 2-3 months after stopping prednisone therapy in patients with still active eye disease (GAG, 109.9 +/- 10.51; CA, 63.8 +/- 7.34; DS, 24.1 +/- 5.07; HA, 22.0 +/- 6.28 mg/24 h). 5. This sensitive method determines the nature of renally excreted GAGs, reflecting the aberrant synthesis pattern of fibroblasts in patients with Graves' disease.

Acute Disease↗