[The quality of life of patients in long-term forensic psychiatric care]. / Kwaliteit van leven van patiënten in de langdurige forensische psychiatrie.

BACKGROUND: Quality of life (QoL) is an important issue in long term forensic psychiatric care (LFPC).
AIM: To provide an overview of the knowledge that has been obtained over the last few years about patients' QoL in LFPC.
METHOD: The quality of life in LFPC has been researched every year since 2007. The research has involved the use of the Forensic Inpatient Quality of Life Questionnaire (FQL) which was developed specifically for patients in LFPC. During the longitudinal research project several studies were conducted in order to identify some of the factors that possibly define patients' QoL.
RESULTS: The QoL of patients in LFPC seems to depend less on patient characteristics and more on the environmental circumstances and on the degree to which the patients have accepted these circumstances. Research has also shown that professional carers do not seem to be sufficiently aware of the QoL of their patients.
CONCLUSION: The fact that it is mainly environmental circumstances that are being associated with QoL offers a positive perspective on improving/optimizing QoL of patients in LFPC. Professional carers could, for instance, be trained to discuss QoL with their patients in a structured manner. This would enable carers to identify potential aspects that require further improvement and to optimise these aspects in discussion with their patients.

Surface hydrophobicity enhances corticosterone incorporation in Candida albicans.

Increased intracellular incorporation of [3H]corticosterone in Candida albicans was dependent on cell surface hydrophobicity. C. albicans strains were grown in culture conditions that induced surface hydrophobicity, and cell wall conditions were evaluated with a polystyrene microsphere assay. Germ tubes, which exhibited the greatest cell surface hydrophobicity, incorporated seven times more radiolabel than the hydrophilic yeast forms. Hydrophobic yeasts contained four times more [3H]corticosterone than their polar counterparts. Hydrophobic yeasts incubated for 48 h on nutrient agar containing corticosterone showed reduced colony size compared with controls. These results demonstrate that environmental factors which augment cell wall hydrophobicity in C. albicans can increase the incorporation of corticosterone, which may influence the metabolic activities in this organism.

Nutrient uptake by Candida albicans: the influence of cell surface mannoproteins.

Numerous ultrastructural and biochemical analyses have been performed to characterize the cell wall composition and structure of Candida albicans. However, little investigation has focused on how subtle differences in cell wall structure influence the intracellular transport of amino acids and monosaccharides. In this study C. albicans 4918 and ATCC 10231 were grown in culture conditions capable of modifying surface mannoproteins and induced surface hydrophobic or hydrophilic yeast cell wall states. Subcultures of these hydrophobic and hydrophilic yeasts were subsequently incubated with one of seven L-[3H] amino acids: glycine, leucine, proline, serine, aspartic acid, lysine, or arginine. The transport of [3H] mannose and [3H] N-acetyl-D-glucosamine were also investigated. This study revealed significant strain differences (P < or = 0.05) between hydrophilic and hydrophobic yeast transport of these nutrients throughout a 2 h incubation. Hydrophilic cultures of 4918 and ATCC 10231 transported nearly two times more (pmol mg-1 dry weight) proline, mannose, and N-acetyl-D-glucosamine than hydrophobic yeast. Hydrophobic cultures preferentially incorporated serine and aspartic acid in both these strains. Strain variation was indicated with the transport of leucine, lysine, and arginine, as follows: experiments showed that hydrophilic 4918 cultures selectively transported leucine, lysine, and arginine, whereas, the hydrophobic ATCC 10231 cultures incorporated these amino acids.

Structural study of vesicular stomatitis virus G protein in the virion envelope.

Some structural properties of the vesicular stomatitis virus (VSV) G protein were examined in virions and isolated envelope fragments. We have shown that in the virion a portion of the G protein extends through the lipid envelope and that this part of the molecule can be cleaved by chymotrypsin. Envelope fragments isolated from VSV without the use fo detergents maintained the structural characteristics of the G protein found in intact virions. In addition, we provide evidence that at least some of the isolated envelope fragments have both sides of the bilayer exposed to added reagents, suggesting that this preparation would be useful for in vitro reassociation experiments.

A 96-well epifluorescence assay for rapid assessment of compounds inhibitory to Candida spp.

A rapid method for the screening of potential antifungal compounds was developed. A variety of compounds were tested against regenerating protoplasts of Candida spp. in a microtiter format. The degree of cell wall formation was assessed by staining with Cellufluor (Polysciences, Inc., Warrington, Pa.), a fluorochrome with known affinity for chitin, followed by determination of fluorescence by using a Dynatech Microfluor reader (Dynatech Laboratories, Inc., Alexandria, Va.). Compounds with known activity against the cell wall or cytoplasmic membrane of fungi inhibited wall synthesis in a concentration-dependent fashion. Treatment with 5-fluorocytosine, however, resulted in no inhibition. In general, protoplasts of C. albicans regenerated more quickly and were more sensitive to the compounds tested than protoplasts of C. tropicalis and C. parapsilosis. While the described method is not specific for a given class of antifungal agents, it may prove useful for testing large numbers of compounds quickly.

Synergistic action of nikkomycins X and Z with papulacandin B on whole cells and regenerating protoplasts of Candida albicans.

Combinations of nikkomycin X (NX) or nikkomycin Z (NZ), known inhibitors of chitin synthesis in fungi, together with papulacandin B (PB), an inhibitor of beta-glucan synthesis, were tested for synergistic activity against four isolates of Candida albicans by using the broth microdilution checkerboard technique and a method to assess the regeneration of cell wall material in protoplasts. The construction of isobolograms from the data generated by the checkerboard determinations revealed a synergistic effect for the two classes of compounds against all strains. The combination of NX and PB was more effective than the combination of NZ and PB, perhaps reflecting the lower Ki value of NX. While the presence of NX and NZ reduced chitin synthesis, as determined by staining with calcofluor white and assaying with a microfluorimeter, cells treated with PB demonstrated an increased synthesis of chitin. Protoplast regeneration experiments using similar concentrations of the two classes of compounds resulted in comparable findings. The combination of NX and PB resulted in a greater inhibition of chitin synthesis than did equivalent combinations of NZ and PB. These data suggest that combinations of agents active against cell wall synthesis in fungi may prove more useful as chemotherapeutic agents than such compounds used singly.

Adherence and receptor relationships of Candida albicans.

The cell surface of Candida albicans is composed of a variety of polysaccharides such as glucan, chitin, and mannan. The first two components primarily provide structure, while the mannan, often covalently linked to protein, constitutes the major antigen of the organism. Mannoproteins also have enzymatic activity (acid protease) and ligand-receptor functions. The complement receptors of C. albicans appear to be mannoproteins that are required for the adherence of the organism to endothelial cells. This is certainly true of the CR3-like protein of C. albicans. Proof that the CR3 is the Candida receptor for endothelial cells is derived from two observations. First, mutants lacking CR3 activity are less adherent in vitro and, in fact, less virulent. Second, the ligand recognized by the CR3 receptor (C3bi) as well as anti-CR3 antibodies blocks adherence of the organism to endothelial cells. The CR2 of C. albicans appears to promote the adherence of the organism to plastic substrates. Unlike the CR2 of mammalian cells, the Candida CR2 recognizes ligands containing the RGD sequence of amino acids in addition to the C3d ligand, which does not contain the RGD sequence. There is uncertainty as to whether the Candida CR2 and CR3 are, in fact, different proteins. A mannoprotein has also been described as the adhesin for epithelial cells. In this case, the receptor has a lectinlike activity and recognizes fucose- or glucosamine-containing glycoproteins of epithelial cells, depending on the strain of C. albicans. The oligosaccharide component of the receptor is probably not involved in ligand recognition and may serve to stabilize the receptor. However, the oligosaccharide factor 6 epitope of mannan may also provide adhesin activity in the recognition of epithelial cells. Mannoproteins can be extracted from cells by a number of reagents. Zymolyase, for instance, tends to remove structural mannoproteins, which contain relatively little protein and are linked to glucan. Reagents such as dithiothreitol, on the other hand, tend to extract mannoproteins containing higher amounts of protein that appear to have receptor function. The mannoproteins of C. albicans are dynamically expressed and may be growth phase and growth form specific.

Chitin synthesis in Candida albicans: comparison of yeast and hyphal forms.

Chitin synthesis was studied in both yeast and hyphae of the dimorphic fungus Candida albicans. Incorporation of N-acetyl-d-[1-(3)H]glucosamine ([(3)H]GluNAc) into an acid-alkali-insoluble fraction was 10 times greater in hyphal-phase cells. A crude preparation of chitin synthetase was obtained from sonically treated protoplasts of both forms of Candida. Enzyme activity, which was determined by using [(14)C]UDP-GLuNAc as a substrate, was exclusively associated with the 80,000 x g pellet from sonically treated protoplasts of both forms. It was determined that enzyme activity (nanomoles of [(14)C]UDP-GluNAc incorporated per milligram of protein) was approximately 2 times greater in hyphae versus yeast cells. Enzyme activity in both yeast and hyphae increased six- to sevenfold when the enzyme preparations were preincubated with trypsin. A vacuolar fraction, obtained from yeast cells but not from hyphae, stimulated enzyme activity when incubated with either yeast or hyphal enzyme preparations. Membrane fractions from protoplasts coated with [(3)H]concanavalin A before disruption were isolated by Renografin density gradient centrifugation. Chitin synthetase activity was preferentially associated with the concanavalin A-labeled fraction, suggesting that the enzyme was located on the plasma membrane. In addition, enzyme activity in protoplasts treated with cold glutaraldehyde before disruption was significantly greater than in protoplasts that were sonically disrupted and then treated with cold glutaraldehyde, indicating that the enzyme resides on the inner side of the plasma membrane.

Regulation and solubilization of Candida albicans chitin synthetase.

A cytoplasmic component which inhibited the activation of chitin synthetase was studied in the dimorphic fungus Candida albicans. The inhibitor was found to be heat stable and trypsin sensitive and was only effective when incubated with a vacuolar protease, an activator of chitin synthetase, before the activation of chitin synthetase. In addition, the particulate chitin synthetase from the yeast form of C. albicans was solubilized by a sodium cholate-digitonin extraction and subsequently was purified approximately 30-fold by Sepharose column chromatography and Amicon XM 100 filtration. Activity of the soluble enzyme was increased by the addition of trypsin or phosphatidyl serine. The molecular weight of the enzyme was estimated to be 400,000.

The use of flow cytometry to monitor chitin synthesis in regenerating protoplasts of Candida albicans.

Flow cytometry was used to monitor chitin synthesis in regenerating protoplasts of the yeast Candida albicans. Comparisons of cells stained with Calcofluor White, a fluorochrome with known affinity for chitin, and cells incubated in the presence of N-[3H]-acetylglucosamine, the precursor substrate for chitin, showed a linear relationship between fluorescence and incorporation of label over time. Changes in both the fluorescence and light scatter of regenerating protoplasts treated with inhibitors of fungal chitin synthase were also quantitated by flow cytometry.

Effect of cerulenin and sodium butyrate on chitin synthesis in Candida albicans.

Experiments were conducted to gain insight concerning the mechanism(s) whereby cerulenin and sodium butyrate affect chitin synthesis in Candida albicans. In vitro studies with isolated membrane-bound chitin synthase from C. albicans, strain 4918, showed that neither agent affected the level of either unactivated or trypsin-activated enzyme activity. Subsequent studies utilizing protoplasts revealed that early in the cell wall regeneration process, cells treated with cerulenin or butyrate synthesized chitin at a rate equal to untreated controls, as measured by the incorporation of [3H]-N-acetylglucosamine (GlcNAc) into acid-alkali insoluble material. However, after 40 min of incubation, the incorporation of [3H]GlcNAc into chitin is reduced in cells treated with either agent. On the other hand, samples taken during the same time intervals and analyzed by flow cytometry suggested that the amount of chitin synthesis in treated and untreated cells was identical. A marked decrease in fluorescence was observed in similar experiments using polyoxin D, a direct inhibitor of chitin synthase activity. Experiments that measured uptake of [3H]GlcNAc into both whole cells and protoplasts demonstrated that cerulenin and butyrate had no effect on the transport of the chitin precursor.

[Computer system for the automatic analysis of cath-lab data. Reliability of pattern-recognition and measurements (author's transl)]. / Computersystem für die automatische Analyse von Herzkatheterdaten. Zuverlässigkeit der Kurvenerkennung und -vermessung.

The computer-system for the on-line-analysis of hemodynamic data developed in Aachen enables the clinical user to perform the immediate on-line analysis of ECG, pressure-curves and thermo- or dye-dilution-curves in a dialog mode. The procedure of pressure analysis as well as the calculations by the computer for the individual haemodynamic parameters are described. The comparison of the medical-manual evaluation of the pressure curves on paper-registration and the computer results of the same measurement shows a very good correlation for wave-recognitions and wave-measurements for this system, integrated in the daily routine since 24 months. As well in the application of various fluid-filled catheters used in praxis as in tip-manometers it could be proved for the pressure-analysis in the different positions of the heart, that the computer-system produced reliable evaluations for all catheter materials used. The flexible conception of the computer program with its fast adaption to new problems allows its use not only in the clinical routine, but also and especially in the handling of scientific questions in the frame-work of haemodynamic analysis.

[Detailed analysis of systolic and diastolic parameters in aortic valve disease (author's transl)]. / Detaillierte Analyse systolischer und diastolischer Parameter bei Aortenklappenfehlern.

The on-line computer-system for the analysis of cathlab data developed by us allows the immediate evaluation of the conventional pressure- and valve-opening as well as a new hemodynamic parameters. In addition the volume-analysis is performed by the videometry-program. In simultaneous pressure-volume-registrations the complementary calculation of important energetic items is possible. This expanded analysis by the aid of the computer-system enables a detailed pre- and postoperative study of great clinical-practical and scientific importance.

Treatment of unstable angina pectoris with percutaneous transluminal coronary angioplasty (PTCA).

Percutaneous transluminal coronary angioplasty (PTCA) was performed in 40 patients (34 male, 6 female; 51.0 +/- 8.5 years) with the typical clinical picture of unstable angina. All had a short history of pain (2.9 +/- 2.0 months), angina at rest, transient ST and/or T wave changes during this period, and little or no enzyme elevations. The patients had a total of 41 stenoses (39 single, one double; one main-stem, 26 left anterior descending, 14 right coronary artery). The degree of the stenoses was 95.5 +/- 4.9% (area method) and 81.8 +/- 10.7% (diameter method). PTCA was successfully performed in 26 cases (63%), reducing the stenoses to 61.5 +/- 12.4% (area method) and 39.1 +/- 10.0% (diameter method). One patient (2.5%) received an immediate bypass operation because of an acute vessel occlusion. Eleven of the 14 not successfully treated patients received an aortocoronary bypass within the next three to 35 days. All still had symptoms of unstable angina. Three patients refused operation. Their treatment consisted of nitroglycerin, beta-blockers and nifedipin. Seventeen of the 26 successfully treated patients were restudied after 4.9 +/- 1.7 months. The degree of stenosis had risen to 69.2 +/- 17.4% (area method). While the stenoses in 12 patients were equal or less than before PTCA, stenosis recurred in five cases. Two patients were successfully retreated. PTCA can be performed with a good early success rate and a low concentration rate in patients with unstable angina. Relief of pain and improvement of blood supply to the jeopardized myocardium can be provided immediately and with a limited amount of expense. The method can therefore be regarded first-stage treatment in such patients.