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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 217 records · Page 12Linked to original sources

Treatment of refractory Hodgkin's disease with high-dose cytosine arabinoside and mitoxantrone in combination. Results of a clinical phase II study of the German Hodgkin Study Group.

In the present study, the activity and side effects of high-dose cytosine arabinoside (HD-Ara-C) in combination with mitoxantrone (mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory Hodgkin's disease. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours days 1 and 2 and mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from infections during treatment-induced cytopenia. The predominant toxicity was severe myelosuppression in all patients with major infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic growth factors will be evaluated in subsequent trials.

Adolescent↗

[Fatal pulmonary embolism in venous thrombosis of the leg and pelvis during lysis therapy].

A 19-year-old girl had for four weeks the clinical signs of recurrent pulmonary emboli and deep-vein thrombosis (tachycardia, dyspnoea, right inguinal pain), which had been misdiagnosed. The correct diagnosis was made only after drastic deterioration in her condition following appendicectomy for falsely diagnosed appendicitis. Urokinase infusion (80,000-160,000 IU/h for 11 days) having failed to bring about improvement, much greater than ultra-high much less than thrombolysis with streptokinase was begun (250,000 IU streptokinase over 30 min, followed by 9 million IU over 6 hours). Fatal pulmonary embolism occurred seven hours after the end of the infusion. Autopsy revealed extensive separation of thrombotic material in the pelvic veins. This observation and other reports should serve as a warning against using streptokinase in ultra-high doses if large veins, as those in the pelvis, are involved.

Adult↗

Irradiation of malignant eyelid melanoma with iodine 125 plaque.

We used contact irradiation with iodine 125 seeds to treat a large, exulcerative, nodular, amelanotic malignant eyelid melanoma with metastasis to the regional lymph nodes in an 80-year-old man. The procedure was similar to iodine 125 plaque irradiation of malignant choroidal melanoma; special equipment, however, was needed to protect the eye from radiation exposure. The response of the malignant eyelid melanoma to iodine 125 plaque irradiation was similar to that of malignant melanomas of the choroid. No complications were observed in a follow-up period of 15 months.

Aged↗

[Interstitial radiotherapy with 125I seeds in non-operable and non-radioiodine retaining local recurrences of differentiated and undifferentiated thyroid cancers].

The use of interstitial radiation therapy in the treatment of local recurrence of anaplastic and other carcinomas of the thyroid is discussed on the basis of four cases. 125I seeds were used except in 1 case. All tumours showed no uptake of radioiodine and could not be completely removed by surgery. In three patients local control of the tumour was achieved (longest follow-up 41 months); one patient died 2 months after therapy due to local recurrence.

Aged↗

Dependence of serum erythropoietin level on erythropoiesis in leukemia.

The dependence of the serum erythropoietin (Epo) level on the blood hemoglobin concentration was compared in patients suffering from leukemia and ulcerative colitis. In leukemia, the level of immunoreactive and bioactive Epo was generally much higher than in ulcerative colitis at comparable degrees of anemia. The highest Epo values were found in patients with severe bone marrow insufficiency of erythropoiesis. These findings support the hypothesis that the plasma level of Epo depends not only on the hemoglobin concentration of the blood but is also influenced by the proliferative activity of the erythron.

Anemia↗

Paradoxical sleep-promoting effects of brain extract from paradoxical sleep-deprived rats.

Brain extract was obtained from whole brains of donor rats following four days of paradoxical sleep deprivation (PSD). Intraperitoneal injection of this brain extract in normal (i.e., not pretreated) recipient rats led to a significant increase of paradoxical sleep (PS) which was beginning at the third hour postinjection and still present on the day after treatment. Both PS episode number and PS episode duration were increased by the PSD extract, whereas slow-wave sleep was not influenced. Brain extract of nondeprived control rats, on the other hand, had no significant effects. In the present experiments, an extract volume obtained from two donor brains was transferred to one recipient. Compared to our earlier investigations (one donor brain/one recipient) this higher "dose" of PSD extract exerted a more pronounced and prolonged effect. These results support the idea that some PS-inducing factor(s) accumulating in the brain during PS deprivation may be involved in the regulation of paradoxical sleep.

Animals↗

[Caries epidemiological study of school children of Rems-Murr area].

An epidemiological study on caries in 1,091 primary school pupils in the Rems-Murr area revealed improvement in oral health as compared with results of earlier studies in the Federal Republic of Germany. For example, 31.4% of first-form pupils and 16.1% of fourth-form pupils were shown to have naturally healthy teeth (DMF-T + dmf-t = 0). The average DMF-T(S) values were between 0.39 (0.5) for six-year-olds and 2.02 (2.74) for ten-year-olds. The average percent of treated permanent teeth in six (ten)-year-old pupils was determined to be 20.5 (46.5)%. The pronounced polarisation of the individual values is, however, of of ater significance in developing programmes for caries prophylaxis than are these average values: Only 22% of the children accounted for approx. 70% of the carious, missing or filled permanent teeth. Carious defects in the permanent teeth of six and seven-year-old pupils were found almost exclusively in the fissures and pits of the six-year molars. An improvement in the oral health of the above-named age groups can only be achieved by means of specific and individual prophylaxis programmes.

Child↗

Structural features that underlie the use of bacterial Met-tRNAfMet primarily as an elongator in eukaryotic protein synthesis.

Met-tRNAfMet from Escherichia coli is utilized efficiently as an elongator tRNA during protein synthesis in the rabbit reticulocyte lysate since it rapidly incorporates its methionyl residue into the same tryptic peptides of rabbit globin as the endogenous Met-tRNAmMet. Therefore, it must lack the structural characteristics that prevent the eukaryotic initiator tRNA from entering elongation. In contrast, E. coli Met-tRNAfMet appears to initiate very poorly since, unlike reticulocyte Met-tRNAiMet, it forms no detectable 43 S preinitiation complexes, and only a very small fraction of the methionine it contributes to polyribosomal peptidyl-tRNA is found at the N terminus. The bacterial fMet-tRNAfMet, which cannot elongate, is utilized for polypeptide chain initiation at a much lower level than the formylated Met-tRNAiMet from eukaryotes. The ability of E. coli Met-tRNAfMet to be used as an elongator and fMet-tRNAfMet as an initiator in the reticulocyte lysate may be considerably underestimated because of the rapid enzymatic hydrolysis of these initiator tRNAs in the lysate. The enzyme hydrolyzes fMet-tRNAfMet and Met-tRNAfMet from E. coli in a strictly Mg2+-dependent manner but not the corresponding species from yeast or rabbit reticulocytes. It also hydrolyzes yeast N-acetyl-Phe-tRNAPhe and reticulocyte peptidyl-tRNA, showing that this enzyme--like the eukaryotic protein synthetic machinery--does not readily distinguish the bacterial tRNAfMet from eukaryotic elongator tRNA.

Animals↗

Mechanism of inhibition of eukaryotic translational initiation by the trinucleotide ApUpG.

ApUpG, the oligoribonucleotide homologous to the initiation codon, as well as the tetranucleotides ApUpGpA and ApUpGpG block initiation of protein synthesis in the rabbit reticulocyte lysate. These oligonucleotides are recognized as translational initiation sites by the ribosomes, leading to a very large accumulation of complete, but inactive, 80 S initiation complexes, containing methionylated initiator tRNA and ApUpG in a 1:1 stoichiometry. ApUpG appears to inhibit by competing with endogenous globin mRNA for 80 S ribosomal couples, since the inhibition of protein synthesis by ApUpG can be largely relieved by increasing the globin mRNA. The 80 S.Met-tRNAiMet.ApUpG complexes are not formed in the absence of hemin, demonstrating that their formation requires the active recycling of eukaryotic initiation factor 2. In addition the trinucleotide correctly directs the Met-tRNAiMet into the ribosomal donor site, since the methionyl residue is puromycin-reactive.

Animals↗

Platelet factor 4 and the response to plasma exchange in the treatment of thrombotic thrombocytopenic purpura.

We report two patients with thrombotic thrombocytopenic purpura who were subjected to plasma exchange. In one case, the plasma levels of platelet factor 4, measured shortly after plasma exchange, increased significantly during plasma exchange. This was followed, however, by a failure to respond to therapy. Repeated plasmapheresis over 3 weeks gave no therapeutic benefit and reversible deep coma occurred. This patient recovered completely after treatment with vincristine. In the second patient, a decline in platelet factor 4 was observed after plasma exchange. This was accompanied by improvement of the patient's condition and a slow rise in platelet count. Plasma exchange was again carried out in this patient because of a recurrence of thrombotic thrombocytopenic purpura 3 years later; again decreased platelet factor 4 plasma levels were observed after plasma exchange and again a therapeutic response followed. Platelet factor 4, therefore, seems to be an effective and early index for the therapeutic benefit of plasma exchange in thrombotic thrombocytopenic purpura.

Adult↗

Translocation of c-abl oncogene and PDGFB (c-sis) gene in a case of CML with 46,XY, t(22;22).

In a case of CML with a variant Philadelphia translocation (Ph1 or Ph) t(22;22) (q11;q13) in bone marrow cells and unstimulated peripheral blood cells, no cytogenetically detectable involvement of chromosome 9 was observed. Southern blot experiments using probes specific for bcr and c-sis however revealed rearrangement of the bcr, but not of PDGFB (c-sis) gene. Northern blot analysis of bone marrow RNA showed a very weak signal with the c-sis probe, while in a lymph-node biopsy PDGFB m-RNA could not be detected. Chromosomal in situ hybridization gave evidence for translocation of c-abl from chromosome 9 to Ph and of PDGFB from chromosome 22 to chromosome 9, as the result of a threefold translocation t(9;22;22).

Bone Marrow↗

Are all lymphoid blasts in the cell cycle? DNA synthesis in the lymphoid tissues of the dog.

Labelling index after one or repeated intravenous injections of 3H-thymidine was measured for various subpopulations of lymphatic cells in different canine lymphoid compartments and correlated with cell morphology. High doses of tritiated thymidine were injected and exposure times of up to 211 days were used. The labelling indices of lymphoid blasts were comparable in all tissues investigated. Labelling index varied from 100% in immunoblasts to 4% in small-sized lymphocytes. Approximately 80% of immunoblasts were labelled 1 h after 3H-thymidine application and 100% labelling was obtained after 12 h repetitive 3H-thymidine labelling. In contrast with medium-sized and large lymphocytes, immunoblasts seem to be rapidly proliferating cells in the dog with almost no Go cells.

Animals↗

[No disorder of arachidonic acid-induced thrombocyte aggregation in familial exudative vitreoretinopathy].

Six patients, members of a family with familial exudative vitreoretinopathy (FEVR), were studied to verify whether the disease was associated with a suspected platelet aggregation defect. No hemostaseologic defect was found in either the affected or healthy members of the family; in particular, there were no grounds for suspecting any disturbance of arachidonic acid-induced platelet aggregation.

Adult↗

Molecular biology and nutrition research.

The important advances that have occurred in molecular and cell biology have great potential for metabolic and nutritional research. This review will focus on the application of genetic manipulation to metabolism and nutrition, with special emphasis on the tissue-specific expression and regulation of the newly introduced genes.

Animals↗