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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 73 records · Page 4Linked to original sources

Animal models of allergic and inflammatory conjunctivitis.

Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small number of allergens such as ovalbumin, ragweed pollen or major cat allergens and consecutive challenge. Different animal species have been used so far. Starting with guinea-pig models of allergic conjunctivitis to assess pharmacological aspects, new models including rats and mice have been developed which mimic major features of ocular allergy. The presently preferred species for the investigation of the immunological basis of the disease is represented by murine models of allergic conjunctivitis. In the future, combined ocular, nasal and aerosolic challenges with allergens may provide a model of allergy that encompasses simultaneously the target organs eye, nose and airways with conjunctivitis, rhinitis and asthma.

Allergens↗

Fundamentals of pulmonary drug delivery.

Aerosol administration of peptide-based drugs plays an important role in the treatment of pulmonary and systemic diseases and the unique cellular properties of airway epithelium offers a great potential to deliver new compounds. As the relative contributions from the large airways to the alveolar space are important to the local and systemic availability, the sites and mechanism of uptake and transport of different target compounds have to be characterized. Among the different respiratory cells, the ciliated epithelial cells of the larger and smaller airways and the type I and type II pneumocytes are the key players in pulmonary drug transport. With their diverse cellular characteristics, each of these cell types displays a unique uptake possibility. Next to the knowledge of these cellular aspects, the nature of aerosolized drugs, characteristics of delivery systems and the depositional and pulmonary clearance mechanisms display major targets to optimize pulmonary drug delivery. Based on the growing knowledge on pulmonary cell biology and pathophysiology due to modern methods of molecular biology, the future characterization of pulmonary drug transport pathways can lead to new strategies in aerosol drug therapy.

Administration, Inhalation↗

[Treatment of flexor tendon injuries in children].

In contrast to the standard therapy of flexor tendon injuries in adults, the postoperative treatment program for children remains a controversial topic. Some prefer immobilization therapy in a variety of forms and for different periods of time. Others prefer early mobilization programs. We present results for twenty-eight children with thirty-seven flexor tendon injuries. The average age was 5.8 years. After primary tendon suture in children six years and younger (group A), our postoperative program consisted of immobilization for three weeks. The older children (group B) were treated with an early passive mobilization program. Follow-up examinations were carried out on twenty six of the children at three months and at 3.7 years. Three months after surgery, the children in group A showed only average results while those in group B presented good finger motion. After 3.7 years both groups showed good results.

Adolescent↗

Uptake of vitamin A in buccal mucosal cells after topical application of retinyl palmitate: a randomised, placebo-controlled and double-blind trial.

Retinoids have been reported to produce regressions in metaplastic changes of the mucosal epithelium. In order to define the role of these micronutrients in the prevention of squamous metaplasia of the oral cavity, it is necessary to measure their uptake in target tissues such as the buccal mucosal epithelium. We demonstrated in a trial that retinyl palmitate applied topically via a toothpaste is taken up by buccal mucosal cells in young healthy volunteers. In the randomised, parallel-designed, placebo-controlled and double-blind trial, forty volunteers divided in two groups cleaned their teeth either with a placebo toothpaste or a retinyl palmitate-containing toothpaste (1 mg/g) for 56 d. Buccal mucosal cells samples were taken from the healthy volunteers during the retinyl palmitate application and the following wash-out phase to determine the concentration of retinyl palmitate and retinol by HPLC. Supplementary blood samples were taken from the volunteers on days 0 and 56 to investigate changes in plasma retinyl palmitate and retinol concentrations. Results from only thirty participants (sixteen placebo and fourteen treated subjects) were used in the statistical evaluation as the remaining sample results were spoiled by a technical defect during the HPLC analysis. A significant (P<0.05) uptake of retinyl palmitate in buccal mucosal cells after 7 d and a significant (P<0.05) increase of plasma retinol after 17 d was demonstrated in our present study. The uptake of retinyl palmitate and the following hydrolysis to retinol led to an enrichment of vitamin A in buccal mucosal cells.

Absorption↗

Screening Fanconi anemia lymphoid cell lines of non-A, C, D2, E, F, G subtypes for defects in BRCA2/FANCD1.

Biallelic mutations in BRCA2/FANCD1 were recently recognized as a rare cause of Fanconi anemia (FA). Using immunodetection with an antiserum directed against the carboxyterminus of the BRCA2 protein, we screened 38 lymphoid cell lines from FA patients whom we could not previously assign, via retroviral complementation analysis, to any of six known FA complementation groups (FA-A, -C, -D2, -E, -F, or -G). Three of these 38 cell lines lacked the 380-kDa BRCA2 signal on immunoblots. DNA sequencing showed biallelic compound and truncating mutations in two of the immuno-negative cell lines, whereas a monoallelic frameshift mutation and an amino acid substitution were detected in the third cell line. Our data show that less than 10% of unassigned FA cell lines harbor truncating mutations in BRCA2/FANCD1. This finding strongly suggests the existence of (an) additional, as yet unknown FA gene(s).

Cell Line, Transformed↗

Substance P-induced pulmonary vascular remodelling in precision cut lung slices.

Substance P (SP) levels have been reported to be elevated in animal models of pulmonary hypertension (PH) and chronic administration of SP has been shown to induce PH. In the present study, the role of reactive oxygen species (ROS) as mediators of SP-induced vascular remodelling and PH was analysed. Vascular remodelling was induced in precision cut lung slices by treatment with [Sar9,Met11(O2)]-SP and by hypoxia. Functional analyses were used to study the chronic [Sar9,Met11(O2)]-SP-mediated effects on proliferation and generation of ROS, which is involved in the pathogenesis of PH. The nonpeptide NK-1 receptor antagonist CP 96345 was used to block [Sar9,Met11(O2)]-SP effects. ROS generation and proliferation was assayed by the dichloroflourescein-diacetate method and incorporation of 5-Bromo-2'-Deoxyuridine, respectively. ROS generation was induced by either 1% oxygen (5.8-fold) or [Sar9,Met11(O2)]-SP (8-fold) in normoxia in the alveolar region. [Sar9,Met11(O2)]-SP did not further elevate ROS levels in hypoxia, suggesting an oxygen-dependent mechanism. High ROS levels stabilised hypoxia inducible factor-1alpha and induced proliferation in small vessels (4.3-fold in hypoxia and [Sar9,Met11(O2)]-SP). Both ROS generation and proliferation were blocked in the presence of CP 96345, nitroblue-tetrazolium, N-acetylcysteine- and diphenylene-iodonium. The results presented in this study indicate a role of SP in proliferative events associated with vascular remodelling in pulmonary hypertension.

Animals↗

Aspirin-sensitive rhinitis-associated changes in upper airway innervation.

Aspirin-sensitive rhinitis is the manifestation of aspirin intolerance in the upper respiratory tract. The disease represents a pseudoallergy against aspirin or related nonsteroidal anti-inflammatory drugs. As a major immunomodulatory role for airway innervation has been proposed in airway inflammatory diseases, the present study assessed changes in human nasal mucosa innervation in patients with aspirin-sensitive rhinitis in comparison to a control group. Immunohistochemistry for protein gene product 9.5, tachykinins, calcitonin gene-related peptide, vasoactive intestinal peptide (VIP) and neuropeptide tyrosine was performed on cryostats sections of nasal mucosa and neuropeptide containing nerves were examined independently using a score grading. In comparison to the control, the aspirin-sensitive rhinitis group had a significant increase of VIP-like immunoreactivity in mucosal nerve fibres. In contrast to constant numbers of mast cells, highly significant increases in the numbers of eosinophils were found in the group of aspirin-sensitive rhinitis patients. In summary, the present quantification of neuropeptide-immunoreactivity of mucosal nerves demonstrated differences in the human nasal mucosa innervation between nonrhinitic and aspirin-sensitive rhinitic individuals. These differences may reflect a pathophysiological role of upper airway innervation in pseudoallergic reactions.

Adolescent↗

Hymenoptera sting anaphylactic reactions in the Mediterranean population of Albania.

BACKGROUND: Relatively few studies have examined the relation of different hymenoptera sting reactions. OBJECTIVE: To investigate the relation of anaphylactic reactions against stings of different hymenoptera subspecies in the Mediterranean population of Albania. MATERIALS AND METHODS: A retrospective study was conducted using the clinic files of 111 patients who were diagnosed for hymenoptera sting reactions from 1987 to 1996. Antigens used consisted of purified hymenoptera venom (bee, wasp, and paperwasp). The patients were diagnosed by intracutaneous tests in concentrations of 0.001 microgram/ml, 0.01 microgram/ml, 0.1 microgram/ml, and 1 microgram/ml. RESULTS: The median age of the patients was 27 years. 57% of stings occurred between 20 to 40 years of age. The majority of anaphylactic reactions were recorded during the months of June to October, 81% of the patients were admitted to the hospital due to Mueller grade II to III reactions. In 26% of all cases, crossreactions (bee-wasp 16%, bee-wasp-paperwasp 7%, wasp-paperwasp 2%, bee-paperwasp 1%) were found. Of all anaphylactic reactions, 64% were attributed to bees, 24% to wasps, 8% to both bees and wasps, and 2% to paperwasps. CONCLUSIONS: In contrast to industrialized countries such as the United States or Western Europe where urban populations predominate, reactions to bee venom were more prevalent in the present study population.

Adolescent↗

Determination of vitamin A palmitate in buccal mucosal cells: a pilot study.

We report in our present pilot study on the uptake of retinyl palmitate and its formation to retinol in buccal mucosal cells. Retinoids are able to change metaplastic lesions in several tissues. Prior to any clinical evaluation it is necessary to measure its uptake in target tissues such as the buccal mucosal epithelium. In this pilot study 12 volunteers creamed the inside of their cheeks lightly with a 0.1% retinyl palmitate containing toothpaste for 10 days followed by a wash out phase. On day 0, 3, 7, 10, 17 and 21, buccal mucosal cell samples were taken from volunteers and the uptake of retinol and retinyl palmitate was determined by HPLC analysis. An uptake of vitamin A was demonstrated in all volunteers. Comparing day 0 to day 3 a significant uptake of retinyl palmitate (p<0.05) was detected and comparing day 3 to 17 and 21 a significant decrease (p<0.05) during growth and differentiation of the mucosal epithelium could be seen. The subsequently formed retinol showed an increase but no statistical significance was determined. - The uptake of retinyl palmitate and the formation to retinol led to an enrichment of vitamin A in buccal mucosal cells. In this way metaplastic alterations of the buccal mucosal epithelium might be prevented or reversed by the application of topical retinyl palmitate.

Adult↗

Glucose encapsulation in catanionic vesicles and kinetic study of the entrapment/release processes in the sodium dodecyl benzene sulfonate/cetyltrimethylammonium tosylate/water system.

The sodium dodecyl benzene sulfonate (SDBS)/cetyltrimethyl-ammonium tosylate (CTAT)/water ternary system has previously been shown to give rise to the formation of vesicles for well-defined compositions requiring an excess of one of the surfactants over the other. Two types of vesicular systems can thus be obtained (named V(+) and V(-), depending on the nature of the excess surfactant, i.e., CTAT or SDBS, respectively). In addition, the pure ion-pair amphiphile (IPA) can be obtained after removing the counterions. These different systems (V(+), V(-), and IPA) were investigated in regards to their ability to susbtantially retain a hydrophilic probe such as glucose. The influence of the initial glucose and surfactant concentrations was studied, and dialysis experiments were conducted with a view to determine the kinetics of glucose entrapment and release by the vesicles and, thus, to assess the possibility of a long-term encapsulation. The results indicate that all the vesicular systems studied here are characterized by quite a high permeability of the amphiphilic bilayer. However, SDBS-rich (V(-)) and IPA vesicles proved to be less permeable than CTAT-rich (V(+)) vesicles.

Benzenesulfonates↗

[Outcome of long-term intensive therapy of surgery patients].

OBJECTIVE: The treatment of severely ill patients remains a medical and human challenge. The aim of the study was to determine the survival rate of patients with prolonged intensive care unit (ICU) treatment. Additionally, the somatic, psychological, and social sequelae of the survivors should be determined. METHODS: Data of all patients who stayed for at least 30 consecutive days on a surgical ICU were evaluated with respect to age, sex, diagnosis on admission, APACHE II-Score, ISS, pre-existing diseases, therapeutic procedures, complications, organ dysfunctions, and mortality. The survivors passed a follow-up examination after 35 +/- 14 months. This included somatic, psychological, and social parameters. RESULTS: Data of 101 patients were analysed (m/f: 78/23, mean age: 49.9 +/- 18.2 years, mean stay on ICU: 57 +/- 37 days, trauma patients: 46%). 31 subjects died on the ICU. Until the follow-up, another 24 patients deceased. Thus, the total mortality rose to 55%. Age, diagnosis on admission and severity of organ failure influenced the ICU mortality. Concerning the mortality after discharge, age, pre-existing morbidity and diagnosis on admission affected the outcome. 41 of the remaining 46 patients (89%) underwent the follow-up. Nearly half of them showed no or minor signs of impairment in any of the investigated areas. One third had severe handicaps. Trauma patients had the lowest mortality rates but showed worse results in rehabilitation. CONCLUSIONS: The mortality after prolonged ICU-treatment is substantially higher compared to average ICU patients. However, having survived the acute phase of the illness, successful rehabilitation in somatic, psychic as well as social terms could be performed to a considerable extent. This outcome is comparable to the one of other ICU populations. The results encourage to a consequent use of all medical options.

Adult↗

[HIV-associated cerebral toxoplasmosis -- review and retrospective analysis of 36 patients].

Highly active antiretroviral therapy (HAART) has resulted in a reduction of morbidity and mortality in HIV-associated cerebral opportunistic infection. Before HAART, up to 50% of all HIV-infected patients in Europe developed cerebral toxoplasmosis, an encephalitis caused by reactivation of Toxoplasma gondii infection. Although potent therapeutical options exist, the prognosis is still poor. We describe the course of 36 AIDS patients with cerebral toxoplasmosis and present a review of clinical signs, diagnosis, therapy, and survival times. The main criteria for differential diagnosis from other secondary neuromanifestations such as primary CNS lymphoma, progressive multifocal leukencephalopathy, abscesses, and ischemic infarctions are described. Indications and problems of stereotactic biopsy are discussed.

AIDS-Related Opportunistic Infections↗

Abundant expression of c-Jun in guinea pig sympathetic ganglia under basal conditions and allergen challenge.

Airway hyperresponsiveness, a keystone of allergic asthma, is mediated by the extrinsic airway innervation. As pathophysiological stimuli can induce the expression JUN proteins, which belong to the immediate early gene (IEG) family of transcription factors, the expression of c-Jun was examined under basal conditions and allergen challenge in guinea pig paravertebral and prevertebral sympathetic ganglia by quantitative double-labeling immunohistochemistry. C-Jun immunoreactivity was seen in 78.4 +/- 3.5% under normal and 82.6 +/- 4.6% under allergen-challenged conditions of protein-gene product (PGP) 9.5-positive sympathetic neurons of guinea pig superior cervical ganglia and 73.1 +/- 2.8% (normal) and 76.1 +/- 3.5% (allergen) of stellate ganglion neurons. In the coeliac-superior mesenteric ganglion, 59.5 +/- 5.0% (normal) and 57.5 +/- 4.4% (allergen) of the PGP 9.5-positive sympathetic neurons were labeled for c-Jun. The high basal levels of c-Jun expression indicate that the presence of c-Jun is not exclusively related to noxious stimulation such as allergic airway inflammation in the guinea pig.

Animals↗

[Psychic and somatic findings in jaw or facial pain of unclear origin. Comparison of patients with severe and mild symptoms].

BACKGROUND: Both for medical and dental specialists, patients with facial arthromyalgia (FAM) and acute or chronic atypical facial pain (AFP) often represent a clinical challenge. Only few empirical studies address the possible interaction between facial pain and increased psychosocial stress with a thereby heightened risk for a chronic course of disease. OBJECTIVE: To evaluate whether FAM or AFP - patients initially presenting with high vs. low pain intensity differ in somatic, psychosocial and socioeconomic parameters. METHOD: We chose to study a population with a primary diagnosis of myofascial pain of the jaw muscles or atypical facial pain and excluded patients with disc displacement, acute arthritis and severe arthrosis. Within nine months, 124 consecutive patients with FAM ( n=108) or AFP ( n=16) were referred to the departments of maxillary surgery, dentistry or neurology of two interdisciplinary academic pain centers. Using the patients'ratings on a 100 mm visual analogue scale concerning their pain intensity, the group was divided in a subgroup initially presenting with low (VAS</=5; n=50) and high pain (VAS>5; n=45). Psychometric evaluation was conducted with the SCL-90R (general psychopathology), the State-Trait-Anger-Expression Inventory (STAXI) and a special questionnaire addressing different aspects of chronic pain (modified SBAS-IV). All patients were assessed by a maxillary surgeon/specialized dentist with the help of a detailed, standardized clinical examination (Helkimo-Index). RESULTS: The group of FAM-/AFP - patients according to our inclusion-/exclusion - criteria presenting with a high pain intensity showed more psychosocial withdrawal ( p=0.013), a worse self-rated psychological status ( p=0.033) and a trend towards more somatization ( p=0.093) than patients with lower pain intensity. There was no correlation between initial pain intensity and somatic parameters of disease as assessed by the standardized clinical examination. Low educational status proved to be the best predictor (p<0.001) for belonging to the high (extensive) pain group. CONCLUSIONS: These data suggest that FAM-/ AFP - patients initially presenting with a high pain intensity have an increased risk for psychosocial stress and maladaptive coping behaviour. As both variables are empirically validated risk factors for a chronic course in pain-related disease, these patients should be of special interest for an interdisciplianary therapeutic setting including psychotherapeutic approaches.

Acute Disease↗

Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patients.

Reticular dysgenesis is a very rare congenital immunodeficiency classified within the severe combined immunodeficiencies (SCID) and characterized by impairment of both lymphoid and myeloid cell development. We report our experience in 10 patients with RD, treated between 1979 and 1999 with HLA-haploidentical hematopoietic stem cell transplantation (HSCT). All children but one were symptomatic within the first days of their lives. Five patients required two HSCT. Five patients received conditioning therapy with busulfan (16 mg/kg) and cyclophosphamide. Three of them are alive and well with myeloid and T and B cell lymphoid reconstitution, whereas two patients died (one chronic graft-versus-host disease, one pneumonitis). Transplantation without or with other conditioning regimens in the other five cases led to absent or incomplete engraftment and none of these cases survived. These results demonstrate the mandatory need for intensive conditioning before haploidentical HSCT in RD to achieve full lymphoid and myeloid engraftment.

Bone Marrow Transplantation↗

Fluorescence in situ hybridization vs. epsilometer test for detection of clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori strains in gastric biopsies from children.

AIM: To compare the results of culture and epsilometer test with fluorescence in situ hybridization for the detection of Helicobacter pylori and the presence of clarithromycin-susceptible and clarithromycin-resistant strains in antral biopsies from children. METHODS: Antral biopsies from 149 unselected children were investigated prospectively; 15 had previously received anti-H. pylori therapy. H. pylori status was defined by histology, rapid urease test and 13C-urea breath test. Fluorescence in situ hybridization was applied on fresh tissue with probes specific for the clarithromycin-susceptible wild type and three clarithromycin-resistant mutants. Susceptibility to clarithromycin was tested by epsilometer test in two laboratories. RESULTS: Culture and fluorescence in situ hybridization gave negative results in all 66 H. pylori-negative children (specificity, 100%). Of 83 infected children, cultures were successful in 75 (90%), epsilometer test in 71 (86%) and fluorescence in situ hybridization in 77 (93%). Eleven children (13%) showed discrepant results between the applied methods, indicating mixed infection. Clarithromycin-resistant isolates were identified in 16 of 73 previously untreated children. CONCLUSIONS: Primary resistance to clarithromycin is common (22%) in H. pylori isolates from children living in Germany. Fluorescence in situ hybridization is an excellent, fast method for the detection of H. pylori and clarithromycin-resistant mutants in gastric biopsies. Multiple biopsies identify mixed infections, indicating that clarithromycin-resistant and clarithromycin- susceptible strains are not evenly distributed within the stomach.

Adolescent↗

Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea-pigs.

BACKGROUND: We have previously demonstrated that the administration of nerve growth factor (NGF) to guinea-pigs results in airway hyper-responsiveness within 1 h. OBJECTIVE: In the present study we document the involvement of NGF in the acute allergic airway response. METHODS: Guinea-pigs that are sensitized to ovalbumin show an acute bronchoconstriction directly after challenge with ovalbumin. RESULTS: Intratracheal application of 10 microg of antibodies directed against NGF (anti-NGF) 1 h before the challenge reduces the acute severe bronchoconstriction to approximately 40% and the sustained bronchoconstriction to approximately 20% of the reaction in controls. This shows a high potency of anti-NGF in diminishing the direct bronchoconstriction. Inhibition of the tyrosine kinases of the tyrosine kinase receptor A, the high-affinity receptor for NGF, has no effect on the bronchoconstriction. Therefore, we postulate that the p75, the low-affinity receptor for neurotrophins, is responsible for the acute bronchoconstriction. Our findings suggest a role for NGF in the induction of the acute asthmatic reaction. CONCLUSION: These findings offer a new potential therapeutic strategy for the treatment of allergic asthma.

Acute Disease↗