Determination of RNA-metabolism as indicator of nutritional status.
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Biomedical subjects
Publications and source records attributed to J Müller.
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We examined the effectiveness of a high-dose Immunglobulin therapy in 8 patients with idiopathic thrombocytopenic purpura (ITP) and measured the number, the morphology and the function of Thrombocytes as well as thrombocyte dependent clotting parameters. 0.5 g/kg/B.W. 7s-Immunglobulin (7s-IgG) per treatment led to normal thrombocyte numbers in 7 out of 8 patients. The maximal thrombocyte-rise occurred on the 4th-10th day of treatment. Simultaneously bleeding time, thrombocyte-volume distribution frequency and Ristozetin-ADP and Collagen induced thrombocyte-aggregation normalized-indication as well as cause of the 7s-IgG-therapy are discussed.
A 34-year-old man with chronic inflammatory joint disease and recurrent fever over 6 years was diagnosed as having Still's disease. Treatment with corticosteroids and azathioprine was ineffective. Therefore, infliximab/ methotrexate was started. The patient subsequently developed a wasting disease with rapid weight loss, erythema nodosum, diarrhoea, progressive lymph node enlargement, and a sigmoido-vesical fistula. Histological analysis of several enlarged lymph nodes, the margins of the fistula, and the small bowel established the diagnosis of Whipple's disease (WD). The presence of Tropheryma whipplei (Tw) DNA in the tissues was confirmed by polymerase chain reaction (PCR). Careful re-evaluation of biopsies taken from the ileum and the liver 2 years earlier, which at that time was not judged to be diagnostic for WD, retrospectively showed subtle histological signs of WD and were positive for Tw DNA. In summary, infliximab treatment seems to increase the risk of exacerbation of WD. WD should be carefully ruled out prior to application of tumour necrosis factor-alpha (TNF-alpha) blockade.
The aim of the study was to check the reliability and comparability of different analytical methods for ambient monitoring of carbon disulfide (CS2). A stationary sampling system, consisting of a charcoal sampling tube and pump, and two personal sampling systems, consisting of a charcoal sampling tube and a portable pump and of a diffusive charcoal sampler have been compared. The limits of quantification, within-series precision, between-series precision, recovery, and comparability of the methods were investigated. For passive sampling the recovery was determined by three different techniques. For a sampling time of 6 hours the limit of quantification was 0.2 ppm for the personal sampling and 0.01 ppm for the stationary sampling system. The within-series precision was between 5 and 8%. For personal sampling the between-series precision was between 9 and 12% using a passive sampler. The recovery ranged between 45 and 85% depending on the quotient of eluent volume and charcoal mass. The comparison of the two personal sampling methods in a field study using linear regression demonstrated with statistical certainty an excellent concordance of the methods. The study shows that particularly the method for determining air levels of carbon disulfide by passive sampling is associated with high systematic errors. If these errors are unknown or ignored they will result in highly underestimated exposure data for carbon disulfide.
PURPOSE: The study was undertaken to assess characteristic short-term CT and MR changes in brain tumors following 125I interstitial irradiation. METHOD: Sixteen patients were included who had both CT and MR control examinations at regular intervals over a period of 18 months following treatment. Two groups were distinguished: low grade tumors (11 cases) and high grade malignancies (5 patients). 125I seeds were used as temporary implants. The cumulative dose was 50-60 Gy. RESULTS: In some patients of both groups, a low attenuation spheric structure with a contrast-medium-enhanced ring and a diameter of 6-8 mm was observed. There was no edema around the structure, which represents a zone of tissue necrosis at the site of the temporary 125I implant. Tumors in both groups were completely destroyed, some decreased in size, and others were unchanged. Pseudotumor necrosis with accompanying edema occurred in two patients with low grade astrocytoma, the diameter of which was > 4 cm. CONCLUSION: The behavior of cerebral tumors and their appearance on CT and MR images after interstitial irradiation seem to be variable. Decrease in tumor size may take place at different intervals after therapy. Brachytherapy of tumors with a diameter of > 4 cm may produce space-occupying radionecrosis.
PURPOSE: To assess the effect of maintenance chemotherapy (MT) on growth factors and growth in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twenty-one children (10 girls, 11 boys) with standard risk pre-B ALL treated with chemotherapy had serum insulin-like growth factor-I (IGF-I), serum IGF binding protein-3 (IGFBP-3) levels, and linear growth and weight data measured every 3 months during MT. The levels of the cytotoxic metabolites of methotrexate (MTX) and 6-mercaptopurine (6MP) (i.e., erythrocyte MTX polyglutamates [E-MTX], and erythrocyte 6-thioguanine nucleotides [E-6TGN]), s-aminotransferases, and white blood counts (WBC) were measured at least monthly. RESULTS: At the beginning of MT, the median IGF-I standard deviation scores (SDS) and IGFBP-3 SDS were -0.52 and -0.09, respectively, which declined during MT to -1.67 (P < 0.001) and -1.82 (P < 0.001), respectively. At the time of diagnosis, the median height SDS was -0.4, which declined during MT to a median height SDS of -0.9 at cessation of therapy. No significant correlations were found between growth factor levels, growth and body mass index (BMI) versus the doses of MTX, and 6MP, E-MTX, E-6TGN, s-aminotransferases, or WBC. CONCLUSIONS: A significant decline in IGF-I, IGFBP-3, and growth retardation may not be directly related to the treatment intensity during MT.
We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.
Yeast cultures of Histoplasma capsulatum var. duboisii and H. capsulatum var. capsulatum in collagen containing defined, semi-defined and complex media produced extracellular collagenolytic proteinases, assayed using 4-phenylazo-benzyloxycarbonyl-L-propyl-L-leucyl- glycyl-L-propyl-D-arginine, a specific collagenase substrate. Significant levels of hydroxyproline were measured in the cultures and clear zones of hydrolysis were produced in collagen buffer agar by the crude enzyme preparations. Hydrolysis of casein and bovine serum albumin at pH 8 suggests the presence, in the crude enzymes, of multiple proteinases rather than a collagenase with broad substrate specificity since collagenolytic activity was not detected at pH 5 and above. Collagenolytic activities in the crude enzymes of both fungi were optimal at pH 4, 40 degrees C and were inhibited by EDTA, phosphoramidion and aprotinin indicating a metallo-serine nature. The molecular weights, estimated by column chromatography, were both 17 kD. The enzymes probably constitute a shared antigen. A probable role in the pathogenesis of histoplasmosis is discussed.
Extracellular elastolytic proteinase was produced by yeast cultures of Histoplasma capsulatum var. duboisii and H. capsulatum var. capsulatum in three different induction media, assayed using elastin-orcein as the substrate. Medium-dependent variations in the time-course for enzyme production were observed and no peak was recorded. The proteinases hydrolysed both casein and bovine serum albumin indicating a broad substrate specificity. Both elastolytic proteinases had similar optimum pH (pH 8) and temperature (35 degrees C); over 90% residual elastolytic activity was measured in the crude enzymes of v. duboisii and v. capsulatum after incubation in the pH ranges 4.5-8.0 and 4.0-7.0 respectively, at 4 degrees C for 24 h. The proteinases were not significantly inhibited by any of the tested proteinase inhibitors. The molecular weights, estimated by column chromatography, were 23 kD. A probable role in the pathogenesis of histoplasmosis is discussed.
A new semi-solid culture medium was developed by substituting the agar in Sabouraud glucose medium by Lutrol FC 127 (BASF, Ludwigshafen, Germany). This culture medium can be liquefied by cooling it down from the incubation temperature to 5-10 degrees C, thus allowing the full harvest of fungal mycelium without any contamination by the gelling agent for antigen preparation. More than 25 protein bands with molecular weights in the range of 98 to 12 kDa were fractionated by SDS-PAGE in antigen preparations from Trichophyton mentagrophytes. Hyperimmune antisera were raised in rabbits and used for immunological studies. Heat-inactivated mycelium was used for the absorption of antibodies against heat-stable cell wall constituents. This absorption facilitated the detection of specific protein bands during immunoblotting which revealed 17 protein antigen bands reacting with antibodies over a range of molecular weights from 98 to 24 kDa.
A survey on the use of hair oils for hair dressings by the Indian population revealed that mustard oil is preferred by males and coconut oil by females. Amla oil is used equally by both. These oils contain different percentages of various saturated and unsaturated fatty acids which largely determine their toxicity against dermatophytes. For Microsporum canis, M. gypseum and Trichophyton rubrum, amla oil was most toxic, followed by cantharidine and coconut oil, while Trichophyton mentagrophytes was most susceptible to coconut oil followed by amla and cantharidine oil. Mustard oil showed least toxicity to all four test species. The rarity of tinea capitis in India has been concluded to be due to the common use of hair oils by the Indian population.
Ten saturated and three unsaturated fatty acids over a wide spectrum of their carbon chain length were tested for their fungitoxicity against five dermatophytes. The experiments showed that short chain saturated fatty acids (C 7:0-C 11:0) are more toxic to dermatophytes than long chain ones (> C 12:0). The antifungal activity decreases with increasing carbon chain length in the even-numbered carbon chain series. Odd-numbered carbon fatty acids show irregularities in these respects. Undecanoic acid (C 11:0) is outstandingly most toxic in the C 7:0-C 18:0 series. Polyunsaturated fatty acids are more toxic than their corresponding saturated acids. The per cent growth inhibition decreased from day 4 to day 12 at all concentrations suggesting the degradation and/or utilization of fatty acids by the fungi during the observation period. The results are discussed on the background of the biochemistry of fatty acids.
The mycotic flora of the ears of zoo animals was investigated in a large zoological garden in Germany. Malassezia pachydermatis was isolated from the following animals: big ant-eater, brown bear, common wombat, Eurasian badger, Indian elephant, Mangaliza pig and wide-mouthed rhinoceros. Aspergillus and Penicillium species, yeasts and zygomycetes were also isolated from some animals.
Saccharomyces boulardii (SB) (Saccharomces cerevisiae Hansen CBS 5926) is a yeast widely used in humans for the prevention and treatment of infectious enterocolitis. SB is said also to antagonize Candida albicans when given orally to living organisms. This double-blind trial was performed to determine the effect and tolerance of SB as an oral therapeutic in patients suffering from cystic fibrosis receiving long-term treatment with cephalosporins or cotrimoxazole, by examining C. albicans counts in the intestine. Extensive mycoserological examinations for drug safety evaluation were also performed. To be selected for the study patients had to present C. albicans in their intestinal flora. None of the patients enrolled exhibited clinical symptoms of candidosis. A daily dose of 750 mg (250 mg t.i.d.) of lyophilized SB given for 21 days did not affect the number of C. albicans commensals in those patients. However, the mycoserological data confirmed the safety of SB treatment with respect to a hypothetically possible SB fungaemia and a possible falsification of Candida serology.
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Amorolfin applied in concentrations of 0.1-100 micrograms ml-1 caused considerable damages to the ultrastructure of Trichophyton mentagrophytes: Electron-transparent areas appear in the cytoplasma. The cell wall increases in thickness. Extracytoplasmic membrane vesicles are formed and deposited in the cell wall. Starved fungal cells, with normal ultrastructure, can be found. Lysed, dead cells demonstrate the process of final, vigorous ultrastructural damage. The feature of the damage caused by amorolfin is comparable to that effected by azole antifungals. The characteristics of the ultrastructural changes are similar to those due to amorolfin in the yeast species Candida albicans.