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Biomedical subjects

T Lange

Publications and source records attributed to T Lange.

16 recordsLinked to original sources

Esketamine multi-omic biomarker evaluation in major depressive disorder (EMBER-MDD): concept, objectives and methodologies of a non-clinical investigator-initiated study.

Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EMBER-MDD) is a non-interventional, investigator-initiated, in-vitro study within the EU Psych-STRATA programme, analyzing biospecimens collected in the randomized INTENSIFY study and the mirror OBS-TR cohort after participants complete treatment. EMBER-MDD aims to discover individual-omic and integrated multi-omic (hypothesis-free) biomarkers and signatures associated with TR risk, and molecular correlates of clinical response to esketamine nasal spray versus treatment as usual (TAU). Biomaterials will derive from approximately 420 adults with MDD (estimated n = 210 esketamine; n = 210 TAU) and include whole blood, RNA-stabilized whole blood, plasma and serum, sampled at baseline and, when feasible, during and after treatment (up to ~ 5,040 aliquots stored at - 80 °C). Genomics will use baseline DNA genotyping on Illumina Infinium GSA v3.0+MD arrays; epigenomics will profile genome-wide DNA methylation across time points using MethylationEPIC v2.0; transcriptomics will employ mRNA-seq (NovaSeq X/ X Plus); and proteomics/ metabolomics will be generated using high-throughput Olink and/ or Biocrates platforms. Each layer will undergo state-of-the-art preprocessing and analyses (e.g., GWAS/ PRS, EWAS, differential expression, WGCNA, pathway and network analyses), followed by integrative strategies including QTL mapping (meQTL/ eQTL/ pQTL/ mQTL) and intermediate-fusion machine learning with nested cross-validation, explainable AI (SHAP/ LIME) and treatment-effect modelling. All outputs are research-only and will not support individual efficacy, tolerability, or clinical decision-making. The study will deliver robust biosignatures and mechanistic hypotheses to guide future validation and inform stratified, molecularly guided intervention strategies in subsequent prospective trials. Trial registration number: 2023-506617-21-00 and 2025-178-f-S.

Humans

Growth of human corneal endothelium on altered Descemet's membrane.

To determine whether Descemet's membrane (DM), which is altered by disease, interferes with endothelial cell growth, healthy human corneal endothelial cells were seeded onto DM from normal corneas and diseased corneal buttons from patients with Fuchs' endothelial dystrophy and pseudophakic bullous keratopathy (PBK). DM was first peeled off the corneal specimens and the endothelial cells removed by trypsinization. A suspension of first-passage corneal endothelial cells (2,000 cells/microliters; obtained from donor eye bank eyes and grown in Dulbecco's minimal essential medium with 10% fetal bovine serum and 1.5% chondroitin sulfate) were seeded on DM. Epidermal growth factor (10 ng/ml) and insulin (1 U/ml) were added to the medium after seeding cells on the DM. The cells attached and flattened within 1 hour and reached confluency in 1 week on normal DM. Cells grown on DM from corneas of patients with Fuchs' endothelial dystrophy also flattened and grew to confluency in 1 week. Cells grown on DM from corneas of patients with PBK did not grow to confluency. Further studies with bovine and rabbit corneal endothelial cells showed similar growth pattern to human cells. These data indicate that DM from corneas of patients with Fuchs' dystrophy does not interfere with the growth of corneal endothelial cells but that DM from corneas of patients with PBK does interfere with cell growth.

Animals

[The pathologically changed Descemet membrane. Cultivation of human corneal endothelium on transformed membrane].

Corneal endothelial diseases are connected with structural and biochemical changes of Descemet's membrane (DM). Little is known about the possible effects of these changed basement membranes. In the present study we investigated the influence of changed DM on endothelium. Human corneal endothelial cells were cultured on DM of healthy corneas as well as corneas with Fuchs' endothelial dystrophy or bullous keratopathy, and cell growth and morphology were compared. On healthy DM, cells formed a confluent monolayer within 4 days. Cells cultured on Fuchs' DM showed a similar pattern. The polygonal cell pattern was interrupted merely in the area of the guttae, which were covered by cell processes alone. Culturing cells proved to be difficult on DM from corneas with bullous keratopathy. Even though the cells attached to the DM, they did not spread but became spindle shaped and rarely formed intercellular contacts. Even after 7 days no confluent monolayer was established. These results indicate that some though not all pathological DM changes interfere with cell growth.

Adult

Changes of the EMG and its relationship to the cardiopulmonary parameters during two-arm cranking of disabled men.

During two-arm cranking in 5 groups of men (able-bodied and leg-disabled with different states of training; wheelchair-dependents with basket-ball training) the behaviour of parameters of the motor and cardiopulmonary system (iEMG, heart rate, oxygen uptake) was investigated. On the basis of stepwise increasing physical work up to exhaustion the group of swimtrained leg-disabled men showed the highest physical working capacity. The lowest physical fitness was found in wheelchair-dependent men.

Adult

[Acute changes in global and regional systolic heart function caused by pentoxifylline in patients with and without coronary sclerosis].

In 36 patients with angina pectoris during complex invasive diagnostic procedure the changes of global and regional systolic heart function by intravenous application of 200 mg pentoxifylline were examined. We observed a significant decrease of preload (reduction of LVEDP and MCS, LVEDV was not influenced) and an improvement of myocardial pump function, possibly combined with a favourable influence on alterated myocardial blood supply. In case of perfusion disturbances of the LV anterior wall the pentoxifylline injection was followed by signs of coronary-steal-mechanism in the LV posterior wall region. We did not found significant changes of afterload. Thus the acute hemodynamic effects of an intravenous application of pentoxifylline are comparable with those of nitrates and non-glycoside-cardiotonic substances with a predominant myocardial effect.

Coronary Artery Disease

[Effects of pentoxifylline on diastolic heart function in patients with angina pectoris and an increased left ventricular wall mass].

The combination of coronary heart disease (CHD) with increased left ventricular wall mass (LVWM) appears associated with prolonged isovolumetric relaxation (IVR) and consequently, alterations in the rapid filling phase. Methylxanthine-substances may improve relaxation through inhibition of phosphodiesterase activity. Accordingly we examined multiple indexes of left ventricular diastolic function before and after administration of 200 mg pentoxifylline (Trental) intravenously to 18 patients (51.3 +/- 9.0 years, 15 males, three females) with stable angina pectoris and positive exercise-ECG in NYHA class I or II and LVWM greater than 160 g (n = 9) and less than or equal to 160 g (n = 9). Left ventricular pressure (P) and volume (V) measurements were made with a high-fidelity-micromanometer before and twelve minutes after administration of pentoxifylline. The time constant of left ventricular isovolumic relaxation (T), usual global left ventricular volumes and derived indexes such as peak filling rate (PFR), time to peak filling rate (TPFR), segmental (relaxation and rapid filling phases) and total pressure-volume relationship before and after pentoxifylline were calculated. Significant differences between these two groups (greater than/less than or equal to 160 g LVWM) were found for end-diastolic volume (68.7 +/- 19.0 to 90.8 +/- 22.6 ml/sqm), end-systolic volume (21.7 +/- 16.0 to 36.1 +/- 14.7 ml/sqm), end-diastolic pressure (15.0 +/- 4.8 to 15.7 +/- 5.1 mm Hg), PFR (3.25 +/- 1.18 to 2.66 +/- 0.71 s-1), T (46.0 +/- 5.7 to 52.7 +/- 7.2 ms), the linear regression of lnP-V (lny = -0.117 x + 4.59 to lny = -0.091 x + 4.75) in the IVR-phase (dp/dtmin less than or equal to x less than or equal to 80 ms) (leftward shift in p-V-relationship when less than or equal to 160 g) and the complet p-V-areas. After pentoxifyl-line-administration there were significant decreases in T in patients with increased LVWM (52.7 +/- 7.2 to 47.7 +/- 5.9 ms) and the P-V-product over the time in the rapid filling phase in patients with LVWM less than or equal to 160 g. Total peripheral resistance and heart rate did not change. These changes in parameters of left ventricular diastolic function in combination with significant improvement of pump function especially in patients with LVWM greater than 160 g after administration of pentoxifylline suggest that improved diastolic function is the result of a direct myocardial effect of pentoxifylline.

Adult

Antibacterial efficacy of Fabry's tinctura on the resident flora of the skin at the forehead. Study of bacterial population dynamics in stratum corneum and infundibulum after single and repeated applications.

The in-vivo antibacterial activity of Fabry's tinctura (FT), a 3 w% salicylic acid, 1 w% phenoli liquefacti containing 50 v/v% isopropanol used in dermatology for the treatment of erythrasma, pityriasis versicolor, acne vulgaris a.o. on the human resident skin flora was assessed by a new test method in comparison to 60 v/v% isopropanol. The test method consists of a detergent scrub method (DSM) in combination with the cyanoacrylate method (CAM) thus allowing the quantitative determination of bacterial densities in two depth compartments of human skin, separately for bacterial genera. The most important innovation of this test method is that its arrangement, especially the separate evaluation of the genera of the resident flora, makes it possible to examine the ability of an antimicrobial agent to invade different depth compartments by its bioactivity against the resident flora and to measure short-and-long-term efficacies under physiological conditions. Our findings in 120 volunteers indicate that compared to 60% isopropanol FT is able to reduce bacterial density in superficial and deep skin compartments immediately after a single application equally well, but for a significantly longer period. In repeated applications, 60% isopropanol does not produce a cumulative or long-lasting effect, but it causes an abundant rebound growth of Propionibacterium spp. in the lower skin compartment. FT, however, shows a cumulative antibacterial effect at the surface and in the depth persisting up to four days after the last application. It is concluded that by its salicylic acid and phenolic content FT is an effective drug for the topical antimicrobial therapy of skin diseases.

1-Propanol

[Clinical use and comparative study of Ulmer drainage and of the usual Redon tissue drainage].

After discussing the shortcomings of the usual Redon drainages and the description of our own technique of vacuum-tissue suction drainage, there follows a report about a comparative examination between Redon drainages and the new 'Ulmer drainage'. Up to now the superiority of the Ulmer drainage was proven only by calculation and experiment, now this fact can be fully confirmed by a succession of clinical examinations. By inserting both types of drainages in one surgical wound, the Ulmer drainage delivered on the first day 1.5 times; on the second and third day, almost 2.5 times the amount of secretion compared with the usual Redon drainage.

Clinical Trials as Topic