Severe Stevens-Johnson syndrome induced by contrast medium iopentol (Imagopaque).
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Child↗
Biomedical subjects
M Hofer
Publications and source records attributed to M Hofer.
Effects of stable adenosine receptor agonists on bone marrow hematopoietic cells as inferred from the cytotoxic action of 5-fluorouracil.
The aim of the study was to investigate the effects of stable adenosine receptor agonists on bone marrow hematopoiesis by utilizing the model of hematopoietic damage induced by 5-fluorouracil (5-FU), a cycle-specific cytotoxic agent. Effects of a non-selective agonist NECA activating all the known adenosine receptors (A1, A2A, A2B, A3) and of the selective agonists for A1 (CPA), A2A (CGS 21680), and A3 (IB-MECA) adenosine receptors were investigated. Experiments were performed with B10CBAF1 mice under in vivo conditions. Adenosine receptor agonists were given in single injections before 5-FU administration and the effects were determined 4 days later. The numbers of femoral marrow nucleated cells and hematopoietic progenitor cells (CFC-GM and BFU-E) were taken as indices of the effects. The non-selective agonist NECA given at a dose of 200 nmol/kg induced biphasic time-dependent effects, i.e. protection and sensitization, when given 10 h and 22 h before 5-FU administration, respectively. The use of isomolar doses of selective receptor agonists indicated that the protective effects of NECA were induced by activation of A2A and A2B receptors, while the sensitizing action of NECA was mediated via A3 receptors. In addition, it was observed that A1 receptors induced protection when activated by administration of CPA 22 h before 5-FU. These findings are discussed with respect to the action of adenosine receptor agonists on the cell cycle state and on the cell cycle-independent cellular protective mechanisms.
Adenosine↗
Elevation of extracellular adenosine mobilizes haematopoietic progenitor cells and granulocytes into peripheral blood and enhances the mobilizing effects of granulocyte colony-stimulating factor.
We tested the capabilities of drugs elevating extracellular adenosine and of granulocyte colony-stimulating factor (G-CSF), given alone or in combination, to mobilize haematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) and granulocytes into peripheral blood. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP) serving as an adenosine prodrug. DP + AMP, G-CSF or all these drugs in combination were administered either singly or repeatedly in a 4-d treatment regimen. Elevation of extracellular adenosine was found to mobilize significantly both GM-CFC and granulocytes after both single and repeated administration of DP + AMP. These results show that the elevation of extracellular adenosine presents a potent mechanism for mobilization of GM-CFC and granulocytes into the blood. When the combination of DP + AMP + G-CSF was given under the 4-d regimen, the mobilizing effects of its administration were additive when compared with those of DP + AMP alone or G-CSF alone. The observed ability of the drugs elevating extracellular adenosine to enhance the mobilizing action of G-CSF points out possible practical utilization of the findings presented here. This conclusion is further supported by the results of an additional experiment which indicate that blocking of haemodynamic side effects of drugs elevating extracellular adenosine by noradrenaline does not suppress their mobilizing effects.
Adenosine↗
Effects of adenosine on the growth of murine G:5:113 fibrosarcoma cells in vitro.
It has been observed that adenosine suppresses the growth of G:5:113 murine fibrosarcoma cells in vitro with EC50 of 178 mM. Changes in the cell cycle including decreased percentage of cells in S-phase, increased portion of cells in G0/G1-phase, as well as prolonged generation time were found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, enhanced the growth suppression induced with adenosine in concentrations of 100 and 200 microM. It follows from these results that the action of adenosine on the G:5:113 cells is extracellular, mediated by adenosine receptors. Elevation of extracellular adenosine might serve potentially as an anticancer therapeutic agent.
Adenosine↗
Lipoxygenase inhibitors suppress proliferation of G5:113 fibrosarcoma cells in vitro but they have no anticancer activity in vivo.
Nordihydroguaiaretic acid (NDGA) and esculetin, both nonspecific inhibitors of lipoxygenases (LOX), were found to suppress expressively the in vitro proliferation of fibrosarcoma cells G5:113 in concentrations ranging from 10 to 50 microM. Subsequent flow-cytometric analysis of the cell cycle showed that both these drugs significantly decreased the percentage proportion of cells in the G0/G1-phase and simultaneously increased significantly this proportion in the S-phase. No apoptosis was detected in the whole range of concentrations studied, from 2.5 to 50 mM. On the contrary, in experiments in vivo, neither NDGA nor esculetin had any curative effect if they were repeatedly injected intraperitoneally (i.p.) into mice bearing tumors growing from subcutaneously (s.c.) transplanted G5:113 cells. Pretreatment of the fibrosarcoma cells with NDGA or esculetin in vitro preceding their s.c. transplantation into mice did not result in suppression of the tumor growth, either. Finally, if G5:113 cells were injected intravenously and the mice were subsequently treated repeatedly with i.p. injections of NDGA, decreased survival and increased number of surface lung metastases were observed in the NDGA-treated group. Thus the suppressive action of inhibitors of LOX on the growth of fibrosarcoma cells in vitro was not reflected in their anti-tumor effects in vivo.
Animals↗
Administration of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) and diclofenac in the combination attenuates their anti-tumor activities.
The anti-tumor effects of i.p. administered cyclooxygenase inhibitor - diclofenac and i.v. administered liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were investigated using a s.c. growing murine fibrosarcoma tumor. Tumor growth was assessed by measuring tumor volumes and survival of the mice. Both of the drugs were administered either alone or in combination. Repeated application of diclofenac in two schedules (150 microg/mouse/day for 14 consecutive days or 2 x 150 microg/mouse/week for 4 weeks) or application of liposomal MTP-PE (2 x 20 microg/mouse/week for 4 weeks) starting on day 5 after tumor cell transplantation significantly suppressed the tumor growth and increased the percentage of surviving mice. However, the volume of tumors and the survival time in tumor bearing mice treated with the two agents were similar to untreated counterparts. Thus, these data suggest the anti-tumor activity of either of the two drugs is lost when they are used in combination. Hematological examinations confirmed previously observed hematopoiesis-stimulating activities of the drugs when given alone. However, mutually potentiating effects after combined administration of liposomal MTP-PE and diclofenac were observed only exceptionally. Our findings corroborate the recommendation that the interactions of drugs used for the treatment of tumors must be carefully checked, if the drugs are applied in combination.
Acetylmuramyl-Alanyl-Isoglutamine↗
[Quality control of sonography courses in advanced training of physicians: analysis of present status and potential for improvement].
AIM: Since 1995 sonography represents the diagnostic imaging procedure most commonly applied (52 %) by physicians working in the public health sector. On the account of the high cost of sonography (around 2,5 billion DM in 1998) it seems justified to intensify the quality control of advanced sonography training courses for physicians. This study was set out to evaluate the learning efficiency and teaching quality of sonography training courses for doctors. We also aimed at testing, evaluating and carefully optimising modern concepts for sonography training based on recognised didactic criteria. METHODS: 34 courses in B-mode sonography and colour-Doppler sonography of 5 regional and national institutions were evaluated on the basis of standardised questionnaires by observers taking part in the courses incognito. The control group was formed by 332 physicians taking part in ten sonography courses which were structured in the way of alternating training modules with practical final exams based on OSCE criteria. With the help of modern imaging media it was intended to make these courses as illustrative as possible, including practical exercises in small groups of up to five people. Subsequent evaluation was based on standardised questionnaires. The attendance quota of the participants served as an additional comparative value for the acceptance of different teaching concepts. RESULTS: We observed significant deficits in the didactic concepts of numerous ultrasound courses offered externally: there was a high prevalence of extended frontal teaching with noticeably tiring effects as well as unstructured practical exercises in large groups which resulted in high numbers of absenteeism of the participants. The evaluation of the newly drawn up course concepts, however, demonstrated highly significant and unquestionable advantages of alternating teaching in small groups. DISCUSSION: Background information from the field of pedagogical psychology is supplied and the application of current learning theories to new concepts of ultrasound courses is demonstrated. CONCLUSION: Instructors of sonography courses need to be well trained in modern teaching methods. This study shows a variety of current concepts and provides a list of easily applicable didactic quality criteria for the conception of ultrasound courses.
Curriculum↗
[Didactic training of ultrasound instructors].
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Education, Medical, Continuing↗
Hemopoiesis-stimulating effects and enhanced survival of irradiated mice after peroral or intraperitoneal administration of ultrafiltered pig leukocyte extract (UPLE, IMUNOR).
Ultrafiltered pig leukocyte extract (UPLE, IMUNOR, ImunomedicA, Ustí nad Labem, Czech Republic) administered perorally (p.o.) or intraperitoneally (i.p.) enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow of normal or sublethally irradiated mice and increased survival of mice exposed to a lethal radiation dose. In experiments in vitro, sera of mice treated with UPLE p.o. or i.p. induced GM-CFC colony formation in cultures of normal mouse bone marrow cells, i.e., produced colony-stimulating activity (CSA). UPLE alone did not induce GM-CFC colony growth, i.e., had no CSA. When UPLE alone or sera of mice administered UPLE p.o. or i.p. were added to bone marrow cultures containing suboptimal concentration of recombinant mouse interleukin-3 (rmIL-3), both UPLE and the sera increased the counts of GM-CFC colonies in comparison with cultures containing only rmIL-3, i.e., produced co-stimulating activity (CoSA). Based on the findings obtained in vitro, it can be hypothesized that the described CSA and CoSA of UPLE may play a role also under in vivo conditions; enhancement of the recovery of hemopoiesis suppressed by ionizing radiation may be due to co-operation of the stimulatory effects of UPLE with the action of cytokines endogenously produced in irradiated tissues.
Administration, Oral↗
Hematopoiesis-stimulating and anti-tumor effects of repeated administration of diclofenac in mice with transplanted fibrosarcoma cells.
Positive effects of repeated administration of diclofenac, an inhibitor of prostaglandin synthesis, in terms of prevention of tumor development and stimulation of hematopoiesis have been observed in C3H mice transplanted subcutaneously with G:5:113 fibrosarcoma cells. Fourteen-day treatment with diclofenac (3.75 microg/kg/day) started from day 5 after tumor cell transplantation. Measurements of tumors and hematological examinations were performed on day 30. The results strongly suggest the possibility that inhibitors of prostaglandin synthesis (non-steroidal anti-inflammatory drugs) may be used in oncological practice where the observed effects are highly desirable.
Animals↗
Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience.
The immunogenicity of three currently used hepatitis B vaccines was compared in an unselected study population in an every day travel clinical setting. Five hundred and eighteen vaccinees received Engerix-B (EB), 990 received Twinrix (TWX), and 366 were immunised with Gen-HB-Vax (GHB). Overall, 88.6% of the vaccinees, tested within the first 6 months after completion of the vaccination series, developed protective levels of anti-HBs (> or = 10 mIU/ml). However, GHB recipients showed significantly lower seroprotection rates (SPR) than EB and TWX recipients (79.3% vs. 87.7% vs. 92.3%, P < 0.000001). GMTs for anti-HBs, tested within 6 months after the third vaccination, showed the lowest results in the GHB group, followed by EB and TWX (142 vs. 523 vs. 1008 mIU/ml, P < 0.000001). TWX vaccinees, however, showing a higher antibody decline rate than EB recipients within the first years after completion of the full immunisation course (30% vs. 25%; P = 0.0538). This study confirms an overall good immune response to the 20 microg-dose vaccine, in the course of a regular clinical setting. The significant difference in SPRs and GMTs to the 10 microg-dose vaccine, however, may influence future immunisation practices for the elderly.
Adolescent↗
Epidemiology of childhood arthritis in Switzerland.
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Adolescent↗
Modulation of radioprotective effects of respiratory hypoxia by changing the duration of hypoxia before irradiation and by combining hypoxia and administration of hemopoiesis-stimulating agents.
AIM: Analysis of radioprotective effect of respiratory hypoxia on hemopoietic tissue and enhancement of this effect by hemopoietic activation. MATERIAL AND METHODS: In mice breathing hypoxic gas mixture during total body gamma irradiation the recovery of pluripotent and committed granulocyte-macrophage progenitor cells and animal lethality were determined. RESULTS: In mice forced to breathe 10% O2 and 8% O2 during irradiation, the oxygen tension in the spleen decreased to 40% and 20%, respectively, of control values. Hypoxia mitigated the lethal effect of gamma-rays and improved the recovery of hemopoiesis in compartments of pluripotent and committed progenitor cells. Enhancement of the proliferative activity in hemopoietic tissue by a cytokine (rmGM-CSF) or an immunomodulator (dextran sulfate) increased the effect of hypoxic radioprotection, while elimination of proliferative cells by hydroxyurea decreased the radioprotective effect. Adaptation of experimental animals to hypoxic conditions was found to reduce the radioprotective effect without influencing tissue partial oxygen pressure lowered by hypoxic conditions. CONCLUSION: The data presented confirm the radioprotective effect of 10% and 8% O2 respiratory hypoxia on hemopoiesis. These findings may represent a way out for further experimental and clinical research aimed at considering differential protection of various tissues by hypoxia.
Adaptation, Physiological↗
Quality of life in patients after meningioma resection.
OBJECTIVES: To evaluate quality of life in patients after tumour resection, to assess different dimensions of quality of life, to compare a newly designed questionnaire with the Nottingham Health Profile. SUBJECTIVE: A non-selected neurosurgically treated series of patients with meningiomas was investigated with reference to quality of life as a judgement of one's own needs and concerns and subjective disease dependent perception. METHODS: A postal survey was sent out to 155 patients who underwent resection of a meningioma between 1977 and 1993 at our clinic. The survey consisted of the specifically designed "Innsbruck Health Dimensions Questionnaire for Neurosurgical Patients" IHD(NS) and the Nottingham Health Profile NHP. The data were put into categories and analysed statistically (Chi-square, Mann Whitney U, Kruaskal-Wallis H-tests). RESULTS: 82 patients (53 female, 29 male) responded (response rate 59%). 10 had died and 7 had moved. The majority of patients (50/61% on NHP and 49/59.7% on IHD) had mild to moderate impairment of quality of life. 20% of the patients showed moderate to severe impairment of the dimensions: physical handicap and energy level. Physical impairment correlated to tumour size. This group was characterised by mainly belonging to the over 70ies age group and taking anti-epileptics. CONCLUSIONS: The quality of life impairments in most patients after tumour resection can be classified as mild to moderate. However, other disease and age effects are difficult to distinguish without a control group. The IHD(NS) correlated well with the NHP questionnaire.
Activities of Daily Living↗
Drugs elevating extracellular adenosine enhance cell cycling of hematopoietic progenitor cells as inferred from the cytotoxic effects of 5-fluorouracil.
OBJECTIVE: Our previous studies showed that the combined administration of drugs elevating extracellular adenosine, i.e., dipyridamole and adenosine monophosphate (AMP), enhanced hematopoiesis in normal mice and increased hematopoietic recovery in irradiated mice. In the present study, we have examined the possibility that these effects are due to the adenosine-induced cycling of the hematopoietic progenitor cells. MATERIALS AND METHODS: Experiments were performed under in vivo conditions using B10CBAF1 mice. The cycling status of hematopoietic progenitor cells (CFU-S(day 10), CFC-GM, and BFU-E) was determined on the basis of their sensitivity to 5-fluorouracil (5-FU), a cycle-specific cytotoxic agent. RESULTS: Pretreatment of mice with dipyridamole + AMP enhanced the cytotoxic effects of a single bolus of 5-FU at a dose of 3 mg per mouse. Sensitizing effects of drugs occurred after a delay of several hours and attained a maximum of about 40-60% reduction of the progenitor cells surviving after 5-FU alone. The period of maximum sensitization of CFU-S by the combination of dipyridamole + AMP was shifted to later time intervals as compared with the effects on CFC-GM and BFU-E. Pretreatment of mice with the drugs also aggravated the 5-FU-induced lethality. Reduction of survival was found in mice exposed to two cycles of 3 mg of 5-FU following the pretreatment with dipyridamole + AMP at a time period characterized by the highest fraction of CFU-S in the S phase. CONCLUSIONS: The results suggest that adenosine receptor signaling, induced by the administration of drugs elevating extracellular adenosine, enhances cycling of the hematopoietic progenitor cells. These effects might have pharmacological implications in the therapy of blood disorders.
Adenosine↗
Low avidity of human serum antibodies for Borna disease virus antigens questions their diagnostic value.
Borna disease virus (BDV) can induce neurological disease in animals. Since viral nucleic acid, infectious particles and antibodies recognizing BDV antigens were found at higher frequencies in psychiatric patients than in healthy controls, BDV is suspected to cause psychiatric disorders in humans. However, the human origin of these viruses has recently been questioned. To diagnose BDV infections, sera are usually analyzed for antiviral antibodies by indirect immunofluorescence (IFA) on virus-infected cells. This study reveals that the reactive antibodies in human sera mainly recognized the BDV phosphoprotein, whereas animal sera preferentially detected the viral nucleoprotein. Immunoglobulin (Ig) G in sera of experimentally or naturally infected animals bound to the viral antigen with high avidity, ie resisting 3 M urea, whereas reactive IgG in human sera did not. Longitudinal studies showed that reactive human antibodies persisted for many years without gaining high avidity for BDV antigens, indicating that they were probably not induced by BDV but rather by infection with an antigenically related microorganism of unknown identity or by exposure to other related immunogens.
Animals↗
Noninvasive investigation for renal artery stenosis: contrast-enhanced magnetic resonance angiography and color Doppler sonography as compared to digital subtraction angiography.
INTRODUCTION: The question about the most appropriate non-invasive method for detecting a renal artery stenosis (RAS) when comparing contrast enhanced magnetic resonance angiography (MRA) and color Doppler sonography (CDS) is still under discussion. Therefore we conducted a prospective study in order to evaluate both methods as compared to digital subtraction angiography (DSA). PATIENTS/METHODS: Thirtysix consecutive patients (53,9 +/- 13,7 years) with suspected RAS were investigated. MRA was performed using gadolinium for contrast enhancement. CDS was performed using a 2.5 and 3,5 MHz transducer. A peak systolic velocity (Vmax) >200 cm/sec within renal arteries and/or a side to side difference of the resistive index (RI) of >0,05 were used to discriminate stenosis. A diameter reduction of > or = 60% by DSA was considered a stenosis relevant to the patient. RESULTS: Sixty-eight main renal arteries and 9 accessory vessels were detected by DSA. Twenty main and 3 accessory arteries were found to be stenosed > or = 60%, while 4 main and 1 accessory artery presented with occlusion. MRA detected 70 renal vessels (65 main and 5 accessory arteries). Twenty-one stenosed arteries and 4 occluded vessels were correctly diagnosed by MRA. With CDS 68 renal vessels (62 main and 6 accessory arteries) could be visual- ized out of which 21 stenoses were diagnosed because of increased Vmax and 6 stenoses were detected because of a side to side difference of RI. For main renal arteries sensitivities and specificities were 96% and 86% for MRA and 96% and 89% for CDS. CONCLUSIONS: MRA and CDS are both comparable methods for detection of a renal artery stenosis > or = 60%. Despite several limitations, CDS can at the moment still be favored as a screening method.
Adult↗
Hemopoiesis-stimulating action of adamantylamide dipeptide: kinetics of increase of GM-CFC in femur and co-stimulating activity of serum, role of bone marrow stromal cells.
Chief part of hemopoietic stromal cells in mediating hemopoiesis-stimulating effects of adamantylamide dipeptide (AdDP), a synthetic immunomodulatory compound, has been determined in a series of combined in vivo/in vitro studies. Indirect stimulatory effect of AdDP on proliferation of hemopoietic progenitor cells for granulocytes and macrophages (GM-CFC) was proved to be mediated by the cells of hemopoietic microenvironment growing as adherent stromal cell populations in vitro. These results supplement previously reported findings of a positive role which is played by AdDP at modulating the interplay among stimulatory cytokines and their cellular sources, and are in consent with the idea to introduce AdDP as a constituent of the hemopoiesis- and immunity-stimulating supportive medical care.
Adjuvants, Immunologic↗