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Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 19 recordsLinked to original sources
PubMed1992

Spontaneous echo contrast imaging in infective endocarditis: a predictor of complications?

Infective endocarditis is associated with significant morbidity and mortality. Valvular destruction and congestive heart failure are more common in patients with echocardiographically detectable vegetations. In addition, spontaneous platelet aggregation is increased when vegetations are present on cardiac valves. The aim of the study was to assess the prognostic value of spontaneous echo contrast (SEC) imaging, as SEC is supposed to reflect red blood cell aggregates stimulated by platelet activity. We studied 293 patients with clinical signs of infective endocarditis. Vegetations, attached to the aortic or mitral valve, were found in 130 patients (44.4%) who were followed for a mean period of 12 months. In 34 of these 130 patients (26.2%) SEC was imaged during the initial transesophageal echocardiographic examination. In these patients SEC indicated a prolonged healing of infective endocarditis with a specificity of 91.2%, a sensitivity of 77.3%, a positive accuracy of 77.3%, a negative accuracy of 74.3%. Multivariate analysis revealed that SEC is a risk factor for valve replacement (p less than 0.001) and for embolic events (p less than 0.001), less for mortality (p less than 0.01), and lowest for abscess formation (p less than 0.05). The dose of ADP to induce half-maximal platelet aggregation was significantly lower in patients with SEC (0.71 +/- 0.15 microliters) than without SEC (1.05 +/- 0.12 microliters; p less than 0.05), implying an increased spontaneous platelet aggregation in the presence of SEC. Our data provide evidence that systemically activated coagulation plays an important role in infective endocarditis. SEC, the echocardiographic implication of an increased platelet aggregation, predicts complications such as thromboembolic events and the need for surgery and is closely related to the prolonged healing period of infective endocarditis. In addition to demonstrating vegetations, transesophageal echocardiography provides information helpful in assigning patients to a high-risk subgroup. Transesophageal echocardiography may play an important role in assessing the clinical outcome of these patients.

Adult↗
PubMed1992

Endocrine function in multiple sclerosis.

In 31 patients with multiple sclerosis (MS) the endocrine functions of the hypothalamus, the pituitary and several peripheral endocrine glands were assessed with a combined pituitary test; 3/31 patients had an endocrine disease: one primary hypothyroidism, one primary amenorrhea and one primary male hypogonadism. We found no patient with endocrine disease of the hypothalamus, the pituitary or the adrenals. However, the poststimulatory secretion of cortisol, growth hormone or thyroid-stimulating hormone was impaired in 7/31 patients, suggesting a possible preclinical endocrine insufficiency in these patients.

Adult↗
PubMed1992

The 93-kilodalton protein of Borrelia burgdorferi: an immunodominant protoplasmic cylinder antigen.

Using immunoblots, we identified proteins of Borrelia burgdorferi recognized by sera from 62 patients with either acute or chronic Lyme disease. In all groups studied, the 41-kDa flagellar protein and a relatively minor 93-kDa protein (p93) were the most commonly recognized antigens in patients with acute and chronic disease due to B. burgdorferi. A murine monoclonal antibody (MAb 181.1) was developed against p93, and the antigen was detected by immunoblot analysis in four European and American strains of B. burgdorferi. On two-dimensional gel electrophoresis, p93 had an apparent pI of 6.8. Immunoelectronmicroscopy with MAb 181.1 demonstrated that p93 is located within the protoplasmic cylinder compartment of the organism. The gene encoding p93 was retrieved from a phage expression library. The derived amino acid sequence of p93 confirmed chemical characterization of the antigen, including its amino-terminal peptide sequence. The derived amino acid sequence predicted it to be predominantly alpha helical. A prominent antigenic domain located at the carboxy portion of the protein was recognized by human and rabbit polyclonal antisera and human (MAb D4) and mouse (MAb 181.1) MAbs.

Amino Acid Sequence↗
PubMed1992

PUVA: how to use it for maintenance.

The selection of optimal maintenance therapy for psoriasis needs great dermatologic skill. The choice between topical therapy, photochemotherapy (PUVA), UVB, and immunomodulating regimens alone or in combinations is a balance between cost and benefit. The effectiveness of healing and the tendency to relapse stands against convenience and access of therapy, the patients' motivation, and not least, the risks of side effects. The effective PUVA-maintenance must be reserved for patients who do not experience clearing of their disease on mild topical and UVB regimens.

Combined Modality Therapy↗
PubMed1991

[Malignant lymphoma associated with HIV infection].

The course of disease in 119 HIV-infected patients (117 men, 2 women; median age 38.5 years) with malignant tumours other than Kaposi's sarcoma was analyzed in a multi-centre retrospective study. This was conducted to obtain initial information concerning the incidence, clinical features and results of therapy in HIV-associated neoplasms, especially malignant lymphomas. The most frequent tumour was malignant non-Hodgkin's lymphoma (98 patients, 82.5%), seven patients had Hodgkin's disease, five had solid tumours, four a polyclonal lymphoproliferative syndrome, three an acute lymphocytic leukaemia, and two had other lymphoproliferative diseases. 58% of the non-Hodgkin's lymphomas occurred in patients with marked immunodeficiency, 85% were high grade malignancies and 47% had primary extranodal disease. 56% of primary nodal lymphomas also had visceral spread (Stage IV). Lymphoblastic non-Hodgkin's lymphoma was more common in patients with favourable immunological status, presented less frequently with primary extranodal disease, was diagnosed earlier than other non-Hodgkin's lymphomas, and appeared to carry a better prognosis. 78 out of the 98 patients with non-Hodgkin's lymphoma had been treated, 66 with cytotoxics. The median survival time was 6 months. Longer remission periods, of at least 12 months, were seen in ten of the 78 patients (13%). Despite the overall poor prognosis and the pre-existing immune defect, palliative (chemo-)therapeutic measures are both justified and promising, and may also result in life-prolonging remissions.

Adult↗
PubMed1991

Modulation of coronary circulation and the cardiac matrix by the renin-angiotensin system.

There are short-term and long-term modulations of cardiac function and cardiac composition by the endocrine and paracrine renin-angiotensin system. First, there is an enhancement of coronary vasoconstrictor tone in severe congestive heart failure due to stimulation of this system. Therapeutic interventions that block the RA-system are able to reduce the increased resistance to coronary flow. Second, there is a relationship between the occurrence of arrhythmias and the degree of sympathetic stimulation in congestive heart failure. The renin-angiotensin system may be involved in arrhythmogenesis because of presynaptic modulation of sympathetic neurotransmitter release. However, in the isolated perfused rat heart no class-specific antiarrhythmic properties could be found for ACE inhibitors during progressive myocardial ischaemia. Third, proliferation of the neointima following injury of a coronary artery is at least in part mediated by angiotensin II. Although ACE inhibition was an effective tool in animal experiments to prevent excessive proliferation of the neointima following ballooning, it was less effective in preventing restenosis in man following a repeat coronary angioplasty. Fourth, preferential proliferation of the cardiac interstitium in experimental hypertension has been associated with activation of the renin-angiotensin system. In patients with essential hypertension ACE inhibitors were not only capable of controlling blood pressure but also of normalizing the previously pathological pattern of diastolic left ventricular filling. In summary, by therapeutic intervention that cause a blockade of this system, cardioprotective and cardioreparative processes can be supported.

Angiotensin II↗
PubMed1991

Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment.

A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy.

Adult↗
PubMed1991

Evaluation of customers' complaints about sunscreen cosmetics sold by the Swedish pharmaceutical company.

Sweden's pharmacies hold more than a 1/3 of the country's market for sunscreen cosmetics (sunscreens). Customers complaining of skin problems associated with the use of sunscreens obtained from the pharmacies were offered dermatological investigation and tests with standard allergens and sunscreens. 27 of 58 complaining customers were fully investigated, and another 8 partly tested. 2 disease entities, a burning sensation and erythema for one or a few days, and dermatitis with scaling lasting for up to 3 weeks, were about equally common. Contact or photocontact allergy to 2-hydroxy-4-methoxybenzophenone caused severe contact dermatitis in 3 individuals.

Benzophenones↗
PubMed1990

Regulation of IFN-gamma-receptor expression in human monocytes by granulocyte-macrophage colony-stimulating factor.

The regulation of human IFN-gamma receptor (IFN-gamma-R) expression by granulocyte-macrophage CSF (GM-CSF) was investigated. On monocytic cell lines (U937, HL60) and peripheral blood monocytes, IFN-gamma-binding capacity was down-regulated upon incubation with GM-CSF. Scatchard plot analyses revealed that down-regulation was caused by a decrease in IFN-gamma-R number rather than by a change in affinity. GM-CSF treatment did not reduce IFN-gamma-R-specific mRNA levels, but reduced the half-life of membrane-expressed IFN-gamma-R, indicating a post-translational control of IFN-gamma-R by GM-CSF. Because both IFN-gamma and GM-CSF are crucially involved in activation of monocytic function, the data presented suggest that down-regulation of IFN-gamma-R by GM-CSF may represent a potential negative feedback control of monocyte activation. Further studies of IFN-gamma binding characteristics and isolation of IFN-gamma-R by immunoprecipitation revealed that IFN-gamma binding to human peripheral blood monocytes is mediated by a receptor protein structurally and functionally identical to that previously characterized in several established cell lines of other tissue origin.

Blotting, Northern↗
PubMed1990

Glycosylation of the human interferon-gamma receptor. N-linked carbohydrates contribute to structural heterogeneity and are required for ligand binding.

The contribution of N-linked carbohydrates to human interferon-gamma receptor (hIFN-gamma-R) structure and function was investigated in four tumor cell lines of various tissue origin. Western and ligand blotting of native and deglycosylated, affinity-purified hIFN-gamma-R of the monocytic cell line U937 and the lymphoid cell line Raji revealed that the different sizes of hIFN-gamma-R from U937 (103 kDa) and Raji (90 kDa) cells are reduced upon either metabolic inhibition or enzymatic deglycosylation of N-linked carbohydrates to a common size of the receptor molecule with an apparent molecular mass of 73 kDa for both cell lines, indicating that heterogeneity in hIFN-gamma-R size is largely due to differential glycosylation. In all cell lines investigated, inhibition of N-linked glycosylation or modulation of carbohydrate processing did not prevent receptor transport to the cell membrane, but blocked hIFN-gamma binding capacity of membrane-expressed receptor molecules, as revealed by specific binding of hIFN-gamma-R-specific monoclonal antibody and specific binding of 125I-labeled hIFN-gamma. These data suggest that a lack of complex-type N-linked carbohydrates is associated with a complete loss of receptor function, i.e. high affinity binding capacity. Recovery of hIFN-gamma binding of deglycosylated receptors was achieved upon affinity purification and adsorption to nitrocellulose membranes, indicating that the carbohydrate side chains themselves do not directly contribute to the ligand binding epitope but seem to be essential for appropriate conformation of the receptor protein in the cell membrane.

Alkaloids↗
PubMed1990

Human chromosome 21 is necessary and sufficient to confer human IFN gamma responsiveness to somatic cell hybrids expressing the cloned human IFN gamma receptor gene.

The human interferon (IFN) gamma receptor cDNA has been stably expressed in human/mouse somatic cell hybrids, which differ in their content of human chromosome 21. Despite high affinity IFN gamma binding-capacity of all receptor transfectants, biological responsiveness to IFN gamma, as determined by enhancement of mouse-MHC class I gene expression, required the presence of chromosome 21. These data suggest complementation of at least two functionally distinct components in order to create a biologically active IFN gamma receptor.

Animals↗
PubMed1990

Multiple sclerosis and other immunologic diseases.

A characteristic feature of immunologic diseases is their association with each other. For multiple sclerosis (MS), several retrospective studies reported increased as well as expected coincidence rates with other immunologic diseases. We conducted a prospective case-control study of MS patients and healthy volunteers and found 13/101 MS patients and 2/97 controls with such diseases (P = 0.009, chi-square test), as well as 47/88 MS patients versus 31/95 controls with a variety of circulating autoantibodies (P = 0.004, chi-square test). These results speak for an increased coincidence of MS with other immunologic diseases and support the idea that MS is also an immunologic disease.

Adolescent↗