[From the therapy study to quality assurance in pediatric oncology].
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Child↗
Biomedical subjects
R Fischer
Publications and source records attributed to R Fischer.
Effect of bradykinin on the cytosolic free calcium activity and phosphoinositol turnover in human glomerular epithelial cells.
The effect of bradykinin (BK) on the intracellular free calcium activity [Ca2+]i and phosphoinositide (PI) turnover was investigated in human glomerular epithelial cells (GEC) in culture. Human GEC exhibited a baseline [Ca2+]i of 114 +/- 3 nmol (n = 81). BK (ED50 10(-9) mol/l) caused a rapid and transient increase in [Ca2+]i, which could also be observed in the absence of extracellular calcium. The effect of BK (10(-8) mol/l) on the [Ca2+]i was inhibited by the BK2 antagonist Hoe 140 (IC50 10(-8) mol/l). BK also induced PI turnover in a time- and dose-dependent manner. A transient increase in (1,4,5)-inositol-triphosphate (InsP3) formation from 1,445 +/- 119 to 4,629 +/- 323 cpm occurred after 5 s. Stimulation of protein kinase C (PKC) by short-term preincubation (15 min) of human GEC with phorbol-12-myristate-13-acetate (PMA) induced a dose-dependent inhibition of the BK-stimulated (10(-7) mol/l) inositol-phosphate formation. Downregulation of PKC by preincubation of human GEC with PMA (24 h, 10(-6) mol/l) or inhibition of PKC by pretreatment with staurosporin (1 h, 10(-6) mol/l) resulted in a slight but significant augmentation of the BK-induced InsP3 stimulation. The data indicate that BK induces stimulation of [Ca2+]i and PI turnover via a BK2 receptor in human GEC. PKC might exert a negative feedback function for the BK-induced PI turnover.
Bradykinin↗
Morphological findings in microangiopathic hemolytic anemia.
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Anaphylaxis↗
Molecular farming of recombinant antibodies in plants.
'Molecular farming' is the production of recombinant proteins in plants. It is intended to harness the power of agriculture to cultivate and harvest transgenic plants producing recombinant therapeutics. Molecular farming has the potential to provide virtually unlimited quantities of recombinant antibodies for use as diagnostic and therapeutic tools in both health care and the life sciences. Importantly, recombinant antibody expression can be used to modify the inherent properties of plants, for example by using expressed antipathogen antibodies to increase disease resistance. Plant transformation is technically straightforward for model plant species and some cereals, and the functional expression of recombinant proteins can be rapidly analyzed using transient expression systems in intact or virally infected plants. Protein production can then be increased using plant suspension cell production in fermenters, or by the propagation of stably transformed plant lines in the field. Transgenic plants can be exploited to produce organs rich in a recombinant protein for its long-term storage. This demonstrates the promise of using transgenic plants as bioreactors for the 'molecular farming' of recombinant therapeutics, blood substitutes and diagnostics, such as recombinant antibodies.
Antibodies↗
Extended high frequency audiometry in pre-school children.
Since adequate and reliable earphones are now available and standards have been established, clinical audiometry can be performed at extended high frequencies (EHFs). In the present study, 47 preschool children (aged 4-7 years) were examined with EHFs (8-16 kHz) using the new Sennheiser HDA 200 earphone. The hearing thresholds correspond to those of other studies; the median thresholds and range increase with increasing frequency. The medians and quartiles were: 10 kHz: 25 (5-35) dB(SPL), 11.2 kHz: 35 (20-40) dB(SPL), 14 kHz 40 (30-50) dB(SPL) and 16 kHz: 50 (40-60) dB(SPL). The hearing thresholds could be more reliably determined in the older children (> 5 years) and were 5 dB better than in the younger ones (< 5 years). Thresholds in the 10-12.5 kHz range correspond to those of adults but are more sensitive by 5-12 dB in the 14-16 kHz range.
Adolescent↗
Coordinating affiliated programs in a hospital setting.
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Health Occupations↗
Stereotactic breast biopsy units in the United States.
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Biopsy, Needle↗
Efficacy and safety of pantoprazole in patients with gastroesophageal reflux disease using an intravenous-oral regimen. Austrian Intravenous Pantoprazole Study Group.
BACKGROUND/AIMS: To investigate the efficacy and safety of an intravenous-oral regimen using the gastric proton pump inhibitor pantoprazole. METHODOLOGY: Outpatients, with endoscopically diagnosed moderate or severe gastro-esophageal reflux disease (GERD stage II and III, respectively, Savary-Miller classification), were recruited from ten hospitals or private practice centers and enrolled into an open-labeled study (intention-to-treat population n=110, age 20-88 years; per-protocol population n=98). Patients were treated once daily with 40 mg pantoprazole which was administered as an intravenous injection for the initial 5-7 consecutive days, then as a tablet, for up to 8 weeks. The efficacy parameters were complete healing of lesions evaluated endoscopically after week 4 and 8, and relief from symptoms assessed after week 2 and 4. RESULTS: Complete healing was achieved in 85/98 (87%) and 93/98 (95%) per-protocol patients, after 4 and 8 weeks, respectively. The corresponding results for the intention-to-treat population were 85/110 (77%) and 93/110 (85%), respectively. After 2 weeks of treatment, heartburn, acid regurgitation, and pain on swallowing resolved in 97%, 98%, and 100% of the per-protocol patients, respectively. Faster healing was observed in non-smokers, those infected with Helicobacter pylori, and those with initial GERD stage II. The intravenous and oral administration phases were well tolerated. CONCLUSIONS: Pantoprazole (40 mg), applied as an intravenous-oral regimen to patients with GERD led to fast resolution of symptoms and high healing rates. For patients, temporarily unable to take oral medications, this regimen offers safe and reliable gastric acid suppression and allows the possibility of changing between the oral and intravenous administration without the need for dose adjustment.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Antibody production by molecular farming in plants.
"Molecular farming" is the production of pharmaceutical proteins in transgenic plants and has great potential for the production of therapeutic anti-cancer antibodies and recombinant therapeutic proteins. Plants make fully functional recombinant human or animal antibodies. Cultivating transgenic plants on an agricultural scale will produce almost unlimited supplies of recombinant proteins for uses in medicine. Combinatorial library technology is a key tool for the generation and optimisation of therapeutic antibodies ahead of their expression in plants. Optimised antibody expression can be rapidly verified using transient expression assays in plants before creation of transgenic suspension cells or plant lines. Subcellular targeting signals that increase expression levels and optimise protein stability can be identified and exploited using transient expression to create high expresser plant lines. When high expresser lines have been selected, the final step is the development of efficient purification methods to retrieve functional antibody. Antibody production on an industrial scale is then possible using plant suspension cell culture in fermenters, or by the propagation of stably transformed plant lines in the field. Recombinant proteins can be produced either in whole plants or in seeds and tubers, which can be used for the long-term storage of both the protein and its production system. The review will discuss these developments and how we are moving toward the molecular farming of therapeutic antibodies becoming an economic and clinical reality.
Animals↗
[Occurrence and incidence of leukemic nodules in the brain].
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Brain↗
[A phlebologic dogma concerning the localization of the Cockett's perforating veins].
Such well-known authors as Cockett, Haeger, Kubik and May have reported that the lowest Cockett's perforating vein is located at a level of 6-7 cm, and the second at 13.5-15 cm, the uppermost or third at 18.5 cm and the "24 perforating vein" at 24 cm from the foot sole; all are on the Linton's line. If this is the case, then this information is a help to surgeons looking for these pathogenetically important veins. We have therefore investigated radiological patients (phlebography) and surgical patients in this respect. In contrast to the reports of the authors mentioned, however, we did not find any predilection levels, even when the perforator heights found by means of the lower-leg length (radiological patients) or the height (surgical patients) were corrected or made relative. Our investigations therefore indicate that one cannot rely on the specified predilection level in the localization of these veins. Incidentally, we found the Cockett's perforating veins not at the level of the Linton's line, but on a "lane" with a width of up to 3 cm. It is therefore high time that the phlebological dogma of predilection sites of Cockett's perforating veins be revised.
Evaluation Studies as Topic↗
Enhancement of carcinoembryonic antigen (CEA) expression in colorectal tumors by neuraminidase.
Twelve colorectal carcinomas with transitional mucosa and 10 colorectal adenomas which previously displayed weak or no carcinoembryonic antigen (CEA) expression were selected to verify whether neuraminidase unmasks CEA carbohydrate epitopes and, consequently, enhances the CEA expression. Peroxidase-antiperoxidase (PAP) method was performed on routinely processed tissues, without and with neuraminidase pretreatment of the sections. Lysine, without and with neuraminidase pretreatment of the sections. Lysine, as a modifier of electrostatic charge at cell surface, instead of neuraminidase was used to clarify whether the enzyme yields a specific or non-specific influence on CEA expression. All colorectal tumors exhibited more CEA after neuraminidase pretreatment, while previous negative specimens developed CEA expression. The same effect was observed in some transitional mucosa sections. This has not occurred in normal mucosa, probably owing to a resistant sialylation. The enhancement effect of lysine, although more weakly and not entirely superimposed to that or neuraminidase, suggests non-specific mechanisms of enzyme action. The removal of the negative charge at cell surface, especially due to sialic acid, allows more anti-CEA antibodies to react. The neuraminidase pretreatment of the sections is a useful method to demonstrate the real incidence of CEA in the colorectal tumors.
Adenoma↗
A mathematical model for metastatic growth illustrated by in vivo and in vitro growth of a transplantable mammary carcinoma in mice.
We analysed the growth pattern of metastases in C3H-mice produced by i.v. injection (tail vein) of tumor cell suspensions of mammary carcinoma HB. Although the ordinary Gompertz equation generally corresponds well to tumor growth in animals and men, we found it inadequate to describe the growth of lung metastases in our model. The morphometric analysis and growth kinetics (LI/GF) of the metastases show a biphasic pattern. The first phase is characterized by a strictly avascular growth and nutrition by diffusion, the second phase is initiated by tumor angiogenesis. To analyze these observations we developed a new mathematical equation which fits particularly well to the metastatic growth curve. We conclude that the present model is appropriate for the analysis of tumor angiogenesis, especially to study factors, which influence the development of a tumor specific vascular system.
Animals↗
Preleukemic myelodysplastic syndromes (MDS): pathogenetical considerations based on retrospective clinicomorphological sequential studies.
Analysis of myelodysplastic syndromes (MDS) in 77 patients terminating in "overt" leukemia revealed sequential changes of marrow morphology with respect to cellularity and involvement of lineages, indicating that different "forms" of MDS represent in reality different phases. Three main phases were observed, which occurred in the following non-reversible sequence: (a) hypocellular dysplasia (H), (b) hypercellular dysplasia with predominance of erythropoiesis (E), and (c) with predominance of myelo(mono)poiesis (MM). Published studies suggest that these phases represent different manifestation stages of the stem cell lesion leading to MDS. Manifestation may probably be promoted by factors causing marrow aplasia. Transition to "overt" leukemia in several cases occurred locally, not throughout the whole marrow. In some patients a mature myelo(mono)-cytic cell population showed the capacity for widespread tissue infiltration, characteristic of leukemic cells. This argues against the theory that "overt" leukemia is the result of continuous dedifferentiation in MDS, but favours the concept of multiple initiating "events" leading to evolution of a leukemic subclone within a myelodysplastic clone. A connection between leukemia differentiation and MDS phase, from which leukemia developed, was also observed indicating that the risk of different stem cell subpopulations to become the target of the leukemia initiating "event" varies during the course of myelodysplasia.
Adult↗
Primary myelofibrosis-osteomyelosclerosis (agnogenic myeloid metaplasia): correlation of clinical findings with bone marrow histopathology and prognosis.
A clinicopathological study was performed on 90 patients (39 males - 51 females, age 68 years) with primary (idiopathic) myelofibrosis - osteomyelosclerosis (OMF) in order to correlate laboratory and histomorphological parameters with each other and to calculate factors of prognostic impact on survival. In addition to multiple interactions between various laboratory features, there was a significant correlation between degree of medullary fibrosis and osteosclerotic changes with sizes of spleen and liver, level of LDH and duration of relevant prediagnostic symptoms. In trephine biopsies of the bone marrow, reduction of hematopoietic tissue was assessed by evaluating the amount of fat cells plus the degree of osteosclerotic lesions. This histological parameter did not reveal significant relationships with hepatosplenomegaly, duration of relevant symptoms or length of disease, but was correlated with the clinical findings of bone marrow failure. On univariate analysis, several clinical (age greater than 45 years, presence of relevant prediagnostic symptoms, hemoglobin level less than 9 g/dl, counts of myelo- and normoblasts, thrombocyte count less than 100 and greater than 700 x 10(9)/l, spleen size and LDH level) and histological features (reduction of hematopoiesis, counts for megakaryocytes and lymphoid nodules) were found to exert a predictive value on prognosis. However, on multivariate regression analysis only age remained significant. This result apparently reflects the numerous interactions between the various clinical as well as histological variables tested.
Bone Marrow↗
[Lectin receptors--markers of colorectal adenomatous dysplasia].
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Adenoma↗
The prognostic implication of clinical and histological features in Ph1+ chronic myelocytic leukaemia (CML).
A study on clinical and histological features of prognostic significance was performed in 45 patients with Ph1+ -CML who showed median survival of 36 months. The histological features were evaluated by morphometry of iliac crest biopsies. Among the variables correlated with prognosis, we eliminated those without primary importance by mutual univariate retrospective stratification. Thus a clinical and a histological set of important prognostic criteria was established. Their influence on prognosis proved to be independent of each other and therefore could be used for separate classifications. Clinical classification yielded two groups with different prognosis: compared to the rest of the patients, the prognosis was much worse for those with a spleen size greater than 10 cm, a liver size greater than 2 cm (below costal margin) and greater than 5% circulating blasts plus promyelocytes. The histomorphological classification consisted of three subgroups: a better than average prognosis was found for patients with pseudo-Gaucher cells in the bone marrow, while in the remaining cases the prognosis was worse in patients with a high number of megakaryocytes (greater than 70/mm2) and a low volume ratio of granulopoiesis: megakaryocytes (less than 15). Since liver size was correlated with the duration of prediagnostic symptoms, the clinical classification probably reflects different disease stages, i.e. a later CML diagnosis. However, the histological set of prognostic factors is independent of the length of the prediagnostic period. Consequently, this morphological classification seems to discriminate different subgroups. Another important prognostic factor, marrow fibrosis, was independent of other histomorphological features, and correlated with duration of symptoms. It obviously also indicates more advanced disease.
Adolescent↗
[Pathologic antepartal CTG as a prognostic factor for further development of the child].
A comparison was made between 123 infants with pathologic antepartal cardiotocograms (CTG) during late pregnancy and a corresponding control group of matched individuals with regard to obstetric and neonatal data as well as the subsequent neuromotor development of the infants. The group with pathologic antepartal CTGs contained 14 children with subsequent neuromotor abnormalities (one irreversible spastic diplegia, 13 reversible neuromotor disturbances) as compared to six cases of reversible neuromotor disturbances in the control group with normal antepartal CTGs. When compared to the control group, the group with pathologic antepartal CTGs manifested a significantly higher rate of pathologic intrapartum CTGs, as well as a higher number of clearly depressed neonates and of serious and slight cases of acidosis in the umbilical artery. In cases of neuromotor disturbances and pathologic antepartal CTG, complicated course of pregnancy (toxemia of pregnancy), premature births before the 37th week of pregnancy, and children with a low (less than 2,500 g) and very low (less than 1,500 g) initial weight are all to be found more frequently. There is, moreover, a clear connection between the degree of seriousness of antepartal CTG pathology and the subsequent occurrence of neuromotor abnormalities. The clinical consequences of the results described here include the early use of the antepartal cardiotocogram in cases of complications during pregnancy involving hypoxia (such as toxemia of pregnancy, premature labor, suspected intrauterine retardation of growth), as well as an increase in the frequency of CTG examinations, even to the point of continuous external cardiotocographic observation and, if other gestational complications involving hypoxia, especially the threat of premature birth, arise, the generous use of primary cesarean section.
Brain Damage, Chronic↗