Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results

The prognosis in advanced-stage ovarian cancer remains poor. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and thereby improve prognosis. The overexpression of folate receptor-α (FR-α) in 90-95% of epithelial ovarian cancers prompted the investigation of intraoperative tumor-specific fluorescence imaging in ovarian cancer surgery using an FR-α-targeted fluorescent agent. In patients with ovarian cancer, intraoperative tumor-specific fluorescence imaging with an FR-α-targeted fluorescent agent showcased the potential applications in patients with ovarian cancer for improved intraoperative staging and more radical cytoreductive surgery.     

Simultaneous characterization of efferent and afferent connectivity, neuroactive substances, and morphology of neurons.

We present a method for establishing in a single experiment four characteristics of individual neurons: the efferent and afferent connectivity, the morphology, and the content of a particular neuroactive substance. The connectivity of the neurons is determined by retrograde fluorescent tracing with Fast Blue and anterograde tracing with the lectin Phaseolus vulgaris leucoagglutinin (PHA-L). After fixation, the brain is cut into 300-micron thick slices. Neurons containing retrogradely transported Fast Blue are intracellularly injected with the fluorescent dye Lucifer Yellow to fill their dendritic trees. The slices are then resectioned at 20-40 microns. One section through the soma of a Lucifer Yellow-filled neuron is selected for the detection of a neuroactive substance contained by this cell [immunofluorescence, secondary antiserum conjugated to tetramethylrhodamine (TRITC)]. Using appropriate filtering, it can be determined in the fluorescence microscope whether a Lucifer Yellow-containing cell body has also been labeled with TRITC, i.e., whether it is immunoreactive for this neuroactive substance. The adjacent sections are subjected to dual peroxidase immunocytochemistry with different chromogens to visualize the PHA-L-labeled afferent fibers (nickel-enhanced diaminobenzidine, blue-black reaction product) and to stabilize the Lucifer Yellow (diaminobenzidine, brown reaction product) in the dendrites of the intracellular injected cells. The other sections are used for electron microscopic visualization of the transported PHA-L. The relationships between the PHA-L-labeled afferent fibers (blue color) and the dendrites of the intracellularly Lucifer Yellow-injected, retrogradely Fast Blue-labeled cells (brown color) are studied by light microscopy. The electron microscope supplies ultrastructural data on the PHA-L-labeled axon terminals.     

Nitrification and denitrification by Thiosphaera pantotropha in aerobic chemostat cultures

Abstract: Thiosphaera pantotropha has been reported to denitrify aerobically and nitrify heterotrophically. However, recent evidence has indicated that these properties (particularly aerobic denitrification) have been lost. The occurrence and levels of aerobic denitrification and heterotrophic nitrification by T. pantotropha in chemostat cultures have therefore been re-evaluated. Only low nitrate reduction rates were observed: the apparent nitrogen loss was of the same order of magnitude as the combined error in the calculated nitrogen consumption. However, ¹⁵N mass spectrometry revealed low aerobic denitrification rates (about 10% of the rates originally published by this group). Heterotrophic nitrification rates were about a third of previous observations. N₂ and N₂O were both produced from NH₄⁺, NO₃⁻ and NO₂⁻. Periplasmic nitrate reductase was present in aerobically grown cells.     

Tinnitus Suppression by Intracochlear Electrical Stimulation in Single Sided Deafness – A Prospective Clinical Trial: Follow-Up

IntroductionEarlier studies show that a Cochlear Implant (CI), capable of providing intracochlear electrical stimulation independent of environmental sounds, appears to suppress tinnitus at least for minutes. The current main objective is to compare the long-term suppressive effects of looped (i.e. repeated) electrical stimulation (without environmental sound perception) with the standard stimulation pattern of a CI (with environmental sound perception). This could open new possibilities for the development of a “Tinnitus Implant” (TI), an intracochlear pulse generator for the suppression of tinnitus.ResultsResults show that tinnitus can be suppressed with intracochlear electrical stimulation independent of environmental sounds, even long term. No significant difference in tinnitus suppression was found between the standard clinical CI and the TI.ConclusionIt can be concluded that coding of environmental sounds is no requirement for tinnitus suppression with intracochlear electrical stimulation. It is therefore plausible that tinnitus suppression by CI is not solely caused by an attention shift from the tinnitus to environmental sounds. Both the standard clinical CI and the experimental TI are potential treatment options for tinnitus. These findings offer perspectives for a successful clinical application of the TI, possibly even in patients with significant residual hearing.

Trial Registration

TrialRegister.nl NTR3374     

Stresses in the closed mitral valve: a model study

In the present model study on the closed mitral valve, tensile force in the chordae tendineae is related to transvalvular pressure using a mathematical model of mechanics of the closed mitral valve. Circumferential stress as well as bending stress in the valve leaflets were neglected. Without precisely knowing the mechanical properties of the leaflet material, geometry of the leaflets was estimated by applying Laplace's law, which relates leaflet stress to leaflet curvature. Independent of shape of the mitral valve orifice, under all circumstances tensile force in the chordae tendineae was calculated to be equal or greater than half the force exerted on the mitral valve orifice by the transvalvular pressure.     

The influence of flatworm predation on zooplankton inhabiting small ponds

Experiments were performed in 1977 to determine which large zooplankton in a series of high altitude ponds can be consumed by the predatory flatworm Mesostoma ehrenbergii. This predator consumes Daphnia at a high rate and the fairy shrimp Branchinecta at a low rate, but does not consume Diaptomus. Experiments were performed in 1978 and 1979 to determined the rate of predation on Daphnia in 30 liter tubs and to determine if predation rate is correlated with surface to volume ratio of experimental containers. There is a clear correlation between surface to volume ratio and predation rate. Determinations of Mesostoma and Daphnia densities were made in a series of eight high altitude ponds, and pond surface to volume ratios were determined. Examination of these parameters lends credence to the argument that Mesostoma predation affects Daphnia dynamics in some circumstances. The results suggest that benthic invertebrate predators may affect zooplankton dynamics, especially in shallow ponds.     

Estimates of regional work in the canine left ventricle

Assessment of the magnitude of regional myocardial work requires knowledge of regional fiber stress and fiber shortening. The theoretical development and experimental validation of a method is presented which used values of estimated active and passive fiber stress according to a fluid-fiber model, and measured fiber strain values. This enables the construction of regional stress-strain diagrams, a regional analog of the pressure-volume area model by Suga and co-investigators, which can be linked to regional oxygen consumption. In the left ventricle, either normally or asynchronously activated, the method yields reliable data on strain and active and passive fiber stress. The relation between estimated regional work and myocardial oxygen demand is in quantitative agreement with previously reported relations between global oxygen demand and measured pressure-volume area. During coronary artery occlusion, however, these values were less reliable, which might be due to inaqdequate knowledge of the (passive) material properties of the myocardium.     

Setting critical nutrient values for ditches using the eutrophication model PCDitch

Critical nutrient loads to prevent duckweed dominance loads in polder ditches were assessed using the eutrophication model PCDitch. In this article the ecological target was set at 50% duckweed coverage. This may be very high for ditches with a nature function, but is not unreasonable for ditches in agricultural areas, with upwelling nutrient rich groundwater, run-off and drainage. Since the change from a ditch with submersed vegetation to duckweed coverage is often a sudden shift, the choice of the amount of duckweed coverage does not influence the calculated loading very much. The main topic of this paper is to present a method to calculate critical loads of nutrients when ecological targets have been set. Sediment type, residence time and water depth influenced the critical loading rates. The calculated critical phosphorus load ranged from 1.8 to 10.2 g P m⁻² year⁻¹, while the calculated critical nitrogen load stretched from 12.1 to 43.8 g N m⁻² year⁻¹. The concentration ranges that were derived from the loading rate were 0.19–0.42 mg P l⁻¹ and 1.3–3.3 mg N l⁻¹. Since PCDitch does not distinguish between Lemna spp. and Azolla spp., no definite conclusions were drawn concerning the effects of nitrogen reduction. In a model situation a pristine ditch was loaded with phosphorus, which resulted into complete duckweed coverage during summer within a few years. When reducing the phosphorus load, it took 10 years before the original situation was reached again. Dredging would accelerate the process of recovery significantly, because the water depth would increase and the phosphorus release from the sediments in summer would decrease. Received September 2003; accepted in revised form February 2005