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Biomedical subjects

H Brandt

Publications and source records attributed to H Brandt.

At least 19 recordsLinked to original sources

A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis.

In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.

Adolescent

In vitro studies of the genotoxic effects of bitumen and coal-tar fume condensates: comparison of data obtained by mutagenicity testing and DNA adduct analysis by 32P-postlabelling.

Bitumens contain traces of polycyclic aromatic compounds (PACs), a part of which will end up in the fumes emitted during hot handling of bitumen-containing products, e.g. during roadpaving. Although exposure of workers to these fumes is low, it might lead to health problems. Studies on bitumen fume condensates (BFCs) showed weak to moderate mutagenic activities, but studies on DNA adduct formation have not been reported. Therefore, a study was initiated in which fumes were generated from two road grade bitumens, in such a way that they were representative of the fumes produced in the field. The combined vapour/particulates were tested in vitro for their ability to produce DNA adducts and in modified Ames mutation assays, using a number of different strains. An attempt was made to relate the results to chemical data, such as the content of a number of individual polycyclic aromatic hydrocarbons (PAHs) and with a measure for the total PAC content. As a reference material fume condensate from coal-tar (coal-tar pitch volatiles; CTPV) were subjected to the same tests. All fume condensates tested were mutagenic to all strains and induced the formation of DNA adducts. The patterns of DNA adducts, obtained by 32P-postlabelling, arising from the BFCs were qualitatively different from the patterns of adducts obtained from the CTPVs, implying qualitative differences in the nature of the compounds responsible for the formation of these adducts. This is corroborated by the observation that for BFCs quantitative adduct levels are higher than would be expected based on the PAH content. These data thus indicate that the PAHs analysed are not the sole components responsible for adduct formation from BFCs, but that an important contribution comes from other (hetero- and/or substituted-) PACs.

Animals

Significant inhibition of hybridoma cells by exogenous application of ganglioside GM3, a possible modulator of cell growth in vitro.

Gangliosides of the mouse-rat hybridoma cell line 187.1, which secretes an antibody against kappa-light chain of mouse IgG, were isolated and structurally characterized by biochemical and immunological methods (overlay technique), and fast atom bombardment-mass spectrometry. Exclusively GM3, substituted with C24:1 and C16:0 fatty acid and C18:1 sphingosine, was found in this B cell derived cell line. A GM3(NeuGc) to GM3(NeuAc) ratio (80 to 20), was characteristic for 187.1 cells, and absolute GM3 amounts of about 0.3 mg 10(-9) viable cells were determined. Exogenous application of GM3, which has been isolated from large cell preparations, to 187.1 cells showed growth inhibition in a concentration dependent manner. Using the MTT-assay and the [3H]thymidine incorporation assay, the cells exhibited a strong reduction in metabolic and proliferative activity, respectively, after exposure of cells to GM3. GM3 was applied in concentrations between 3 microM and 30 microM, giving evidence for strong inhibitory effects at 30 microM GM3 and less but significant suppression after application of GM3 concentrations lower than 20 microM. No cellular response was observed at the lowest concentration (3 microM) used in this study. Hybridoma cells as well as other cell types like fibroblasts, muscle cells and endothelial cells, are in general characterized by high expression of the GM3 ganglioside, which is known to act as a modulator of cellular growth in monolayer cultures of adherent cells. Since gangliosides are released to the culture medium by cell lysis, i.e. cell death, and/or by active membrane shedding, the results obtained in this study suggest a growth regulatory role of GM3 in high density hybridoma cell cultures.

Animals

Different distributions of glycosphingolipids in mouse and rabbit skeletal muscle demonstrated by biochemical and immunohistological analyses.

The expression of neutral glycosphingolipids and gangliosides was investigated in mouse and rabbit skeletal muscle by means of biochemical and immunochemical techniques. Neutral glycosphingolipids from muscle of the inbred rabbit strain used in this study showed a simple TLC pattern, comprising mainly monohexosylceramide. In addition to this compound, lactosylceramide, lacto-N-neotetraosylceramide, globoside and Forssman GSL were detected in mouse muscle. The major ganglioside in both species was GM3; GM3 (Neu5Ac) and GM3(Neu5Gc) were found in a 3:1 ratio in mouse muscle, whereas the absence of GM3(Neu5Gc) is characteristic of rabbit muscle. As a general structural feature of all muscle GM3 gangliosides investigated, a C18 fatty acid and C18 sphingosine were the major components besides minor C22 and C24:1 fatty acids of the respective ceramide portions, as revealed by positive and negative ion FAB-MS. alpha 2-3 sialylated lacto-N-neotetraosyl-ceramide (sialylparagloboside) was expressed in both species, whereas the alpha 2-6 sialylated isomeric compound was found only in mouse muscle. Minute quantities of ganglio-series GM1, GD1a, GD1b, and GT1b were detected in muscles from both species. Glycosphingolipid expression could be confirmed immunohistochemically by examining transverse and longitudinal cryosections of skeletal muscle samples. The results provide the basis for the investigation of muscle specific glycosphingolipids that might modulate membrane protein functions in muscle.

Animals

Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation.

The influence of intestinal bacterial decontamination on the occurrence of grades II to IV acute graft-versus-host disease (GVHD) was retrospectively analyzed in 194 predominantly adult patients treated by genotypically identical sibling marrow transplantation under conditions of strict protective isolation and intestinal antimicrobial decontamination. Forty-five patients (23%) developed acute GVHD and univariate analysis identified four features that significantly increased the risk for this reaction: chronic myeloid leukemia as the underlying disease, as compared with all other disease categories (P < .0001); female marrow donors for male recipients, as compared with other gender combinations (P < .005); ineffective, as compared with sustained growth suppression of intestinal anaerobic bacteria (P < .006); and methotrexate as the sole immunoprophylactic compound, as compared with cyclosporine containing regimens (P < .05). Using the duration of anaerobic growth suppression as a time-dependent explanatory variable, proportional hazards regression analysis confirmed these features as independent predictors for acute GVHD with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to 2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3 to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to 2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1 to 1.6) for the donor/recipient gender combination (P < .008), respectively. Best subset selection modeling also identified the quality of anaerobic decontamination as the third most important predictor for acute GVHD, when all four significant features were included. Estimates of acute GVHD stratified by the quality of anaerobic bacterial growth suppression showed a strong influence of anaerobic decontamination in patients burdened by at least one of the other unfavorable factors (P < .009). In conclusion, this study provides strong evidence that sustained growth suppression of intestinal anaerobic bacteria after clinical sibling marrow transplantation can independently modulate the occurrence of grades II to IV acute GVHD, which is in concordance with previous results from animal transplantation models. Antimicrobial chemotherapy specifically targeted to the intestinal anaerobic bacterial microflora may be complementarily useful in preventing acute GVHD and should be investigated in a prospective trial.

Adolescent

Biodeuteration of poly(beta-hydroxybutyrate).

The formation of poly(beta-hydroxybutyrate), PHB, by Rhodobacter sphaeroides and Alcaligenes eutrophus was studied using the following carbon sources and solvents: (1), acetate in H2O; (2), D3-acetate in H2O; (3), acetate in 90 to 92% D2O; and (4), D3-acetate in 90 to 92% D2O. The growth of Rb. sphaeroides cultured under condition (2) showed no apparent deuterium isotope effect, while considerably slowed growth in the presence of D2O was observed under conditions (3) and (4). In all cases, the PHB produced under deuterium enriched conditions was of high molecular weight. Interestingly, comparatively high volumetric formation of partially deuterated PHB was obtained using culture condition (4) for A. eutrophus. Fourier transform infrared spectroscopy (FT-i.r.), pyrolysis gas chromatography mass spectrometry (PGC-m.s.), and nuclear magnetic resonance (n.m.r.) were used to establish the extent and distribution of deuterium in the PHB samples produced. Partially deuterated PHB was obtained in each case, using a deuterium enriched culture. Considerable differences in the extent and distribution of deuterium were found between micro-organisms and culture conditions.

Acetates

Efficacy and safety of itraconazole in the long-term treatment of onychomycosis.

Sixty-one patients with a clinical diagnosis of onychomycosis in finger or toe nails were treated with itraconazole 100 mg/day or griseofulvin 500 mg/day for six to nine months. The infective causes were Trichophyton rubrum, Trichophyton mentagrophytes, or Trichophyton violaceum, and in two cases Candida albicans. A total of 27 finger and 390 toe nails were infected. Statistically significant intragroup reductions from baseline symptom severity values were seen at endpoint (month 6 or 9) for both treatment groups for all parameters: colour change, thickness, brittleness and unaffected area. No clinically or statistically significant differences between the treatment groups were seen at endpoint. However, the itraconazole group continued to improve during the follow-up, while the mean symptom severity ratings remained the same in the griseofulvin group. All itraconazole patients and 85% of griseofulvin patients were rated as cured or markedly improved at endpoint. Nineteen out of 26 evaluable itraconazole patients (73%) remained cured during the three month follow-up period, compared with 12 out of 17 griseofulvin patients (71%). The rather large number of drop-outs, especially among griseofulvin patients, makes it difficult to draw definitive conclusions of the symptom recurrence. Two itraconazole patients stopped medication due to an adverse event, compared to four patients in the griseofulvin group. The clinical laboratory data on itraconazole-treated patients did not show any statistically or clinically significant changes. In conclusion, itraconazole was at least as effective as griseofulvin in the treatment of onychomycosis. The itraconazole group continued to improve after the treatment was stopped. The results show that itraconazole 100 mg/day is safe and efficient in the long-term treatment of fungal nail infections.

Adolescent

Second messenger enzymes in glial cells: a cytochemical point of view.

Knowledge about second messenger metabolizing enzymes in neuroglia is still rather fragmentary. Therefore, the aim of the present investigation was to localize adenylate cyclase, guanylate cyclase, cyclic nucleotide phosphodiesterase and protein kinase A in glial cells of the rat hippocampus and cerebellum. Enzyme histochemical and immunohistochemical methods were used to detect the enzymes at the light and electron microscopic level. Astroglial cells were found to contain all 4 enzymes. Especially the microvascular glial cell processes were reactive. Oligodendroglial cells were only stained for adenylate cyclase acticity. Intracellularly, microtubules and intracellular membranes were frequently stained. The results point to the regulation of glial cell metabolism and of transport processes by cyclic nucleotides.

2',3'-Cyclic-Nucleotide Phosphodiesterases

[Determination of the value of conventional and computer-assisted tomography in examining the thoracic organs].

We compared the results of CT and conventional tomography examinations of the thorax of 137 patients with each other and with the final results. In the diagnosis of bronchial carcinomas we found no significant differences between the two methods. In all other investigated items CT proved to be superior to conventional tomography, especially of the evaluation of mediastinum (90% vs. 35%). We conclude that CT is the method of choice in the staging of intrathoracic tumours and especially in the evaluation of hilar and mediastinal masses and there is no need for conventional tomography in these cases.

Carcinoma, Bronchogenic

Ditrastick combined with UVB. An alternative regimen for plaque psoriasis.

Two comparable groups of 15 out-patients with symmetrical plaque psoriasis were included in an open right-left comparison study. Paraffin based, 3% dithranol (anthralin) sticks (Ditrastick), Orion Pharmaceutica, Espoo, Finland) and 0.5-1% dithranol in white petrolatum were used in combination with UVB. Both suberythema doses and MED doses were used and the effect of UVB-pretreatment was studied. Pretreatment with UVB and combination therapy with dithranol using suberythema doses of UVB seems to decrease dithranol irritation and shorten the treatment time. Preliminary results are given.

Anthralin

[Questionable hyperparathyroidism: diagnostic value of thallium-technetium subtraction scintigraphy].

The diagnostic exclusion of hyperparathyroidism belongs to the standard repertoire of a practicing urologist involved in stone prophylaxis. Primary indicators of hyperparathyroidism are increases in serum calcium and in parathyroid hormone. Additional diagnostic methods are needed, since the methods most often used so far are inadequate, especially insofar as adenomas and ectopic tumors or recurrences can remain unrecognized. Exploratory surgical intervention means a difficult and traumatizing operation. Therefore, a sensitive technique for localization of adenomas is an urgent necessity. Thallium-pertechnetate subtraction scintigraphy was first introduced for localization of an adenoma of the parathyroid by Ferlin's group. This technique yielded better results than any previously known methods, with a success rate of 92%. The object of the present paper is not only to present a method that is not yet sufficiently well accepted among urologists, but also to offer a critical evaluation of the examination results known so far. The method cannot yet make exploratory surgery unnecessary, even when clinical and biochemical examinations give rise to a strong suspicion. However, since ectopic adenomas and possible relapse can be recognized with 90-100% accuracy, which is important in deciding on the surgical strategy, the method should be included in the preoperative diagnostic armamentarium.

Adenoma

[A case report of pharyngeal diphtheria].

Report about a case of toxic diphtheria in a 25-years-old woman. In consideration of new findings about the serum antibody level to diphtheria toxin in the population of the GDR the speciality in this case is described. The risk of possibility on more diseases is demonstrated. In result of all findings will it be necessary, that the disease of diphtheria must be recapitulated. It must bear in mind, that such severe cases can be avoided by systematic revaccination even of adults.

Adult

Efficacy and tolerability of erythromycin acistrate and erythromycin stearate in acute skin infections of patients with atopic eczema.

The efficacy and tolerability of a new erythromycin derivative, erythromycin acistrate (EA), were compared with that of erythromycin stearate (ES) in 42 patients with infected atopic eczema. The dosage of EA was 400 mg tid and that of ES 500 mg tid. The duration of treatment ranged from five to 12 days. The patients were hospitalized and evaluated before treatment and on the last day in hospital. The infective pathogen was usually Staphylococcus aureus in both groups. Without local antibacterial treatment both drugs eradicated the bacteria in more than 60% of the cases. Gastrointestinal side effects were frequently reported with both drugs, more often in the ES- than in the EA-group, but the difference was only statistically significant (p less than 0.05) with respect to diarrhoea. One patient in each group discontinued treatment because of gastrointestinal side effects. No elevations in liver enzymes of clinical significance were reported in either group.

Administration, Cutaneous

Preparation of cell envelopes of large numbers of individual bacterial strains with the use of an automatic cell disruptor.

Analysis of the cell envelopes of large numbers of bacterial strains is used for the epidemiological and taxonomic investigation of clinical, veterinarian, and ecological isolates. Isolation of cell envelopes requires lysis of the bacteria. We developed an apparatus to disrupt bacterial cells of 200 different isolates in suspension by ultrasonication automatically. It is composed of modified standard laboratory equipment (fraction collector, cooling unit, pump), a standard ultrasonifier, and a newly designed control unit, which includes a sampler. This apparatus was applied to the analysis of cell envelope proteins of 96 Haemophilus influenzae strains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis within 3 days after the first culture.

Bacterial Outer Membrane Proteins

Antipsoriatic activity of 10-acyl analogues of dithranol (anthralin). II. Clinical comparison of dithranol and butantrone sticks with special reference to side effects.

Thirty outpatients with limited (under 15% of skin area affected), symmetrical psoriasis of the plaque type were included in an open, right-left comparison study. Paraffin-based, 3% dithranol sticks (Ditrastick, Orion Pharmaceutica, Espoo, Finland) and similar, equimolar 4% butantrone sticks were used. Antipsoriatic activity, staining of the skin and clothes and irritation were the parameters followed up. An overall evaluation was made at the end of the trial. The antipsoriatic activity of dithranol and butantrone was almost equal at equimolar concentrations. Staining of the skin was significantly (at least p less than 0.05) milder with butantrone after 2 to 10 weeks treatment. Staining of clothes was less on the butantrone side for up to three months of use but was thereafter similar to that of dithranol. Irritation caused by butantrone reached its maximum only after 6 to 10 weeks and remained on average below the level of initial dithranol irritation. Six patients discontinued the treatment due to irritation by both preparations. Four patients tolerated better dithranol than butantrone. One patient could not use dithranol but cleared with butantrone. Thus, even if butantrone has an antipsoriatic efficacy almost equal to that of dithranol and is less staining than dithranol, it causes in some patients slowly increasing irritation with Koebner-like deterioration of the disease after some weeks of uneventful overnight use.

Administration, Topical