How does mental health care perform in respect to service users' expectations? Evaluating inpatient and outpatient care in Germany with the WHO responsiveness concept

Background

The official statistics of persons with mental disorders who are granted disability pension (DP) in Russia and Norway indicate large differences between the countries.

Methods

This qualitative explorative hypothesis-generating study is based on text analysis of the laws, regulations and guidelines, and qualitative interviews of informants representing all the organisational elements of the DP systems in both countries.

Results

The DP application process is initiated much later in Norway than in Russia, where a 3 year occupational rehabilitation and adequate treatment is mandatory before DP is granted. In Russia, two instances are responsible for preparing of the medical certification for DP, a patients medical doctor (PD) and a clinical expert commission (CEC) while there is one in Norway (PD). In Russia, the Bureau of Medical-Social Expertise is responsible for evaluation and granting of DP. In Norway, the local social insurance offices (SIO) are responsible for the DP application. Decisions are taken collectively in Russia, while the Norwegian PD and SIO officer often take decisions alone. In Russia, the medical criterion is the decisive one, while rehabilitation and treatment criteria are given priority in Norway. The size of the DP in Norway is enough to cover of subsistences expenditure, while the Russian DP is less than the level required for minimum subsistence.

Conclusion

There were noteworthy differences in the time frame, organisation model and process leading to a DP in the two countries. These differences may explain why so few patients with less severe mental disorders receive a DP in Russia. This fact, in combination with the size of the DP, may hamper reforms of the mental health care system in Russia.     

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.     

Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin.

We compared the pharmacokinetics and the serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Fifteen healthy volunteers received 1 g of cefpirome, ceftazidime, and ceftriaxone intravenously, 500 mg of imipenem-cilastatin intravenously, and 500 mg of ciprofloxacin orally. High-performance liquid chromatographic assays were used to quantitate unchanged antibiotic in plasma and urine. Serum bactericidal activities were determined against six clinical isolates each of Staphylococcus aureus, Enterobacter cloacae, and Pseudomonas aeruginosa by using a modified microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977). Overall, cefpirome exhibited pharmacokinetics similar to those of ceftazidime: half-life (t1/2), 1.95 h; concentration at 1 h (C1h), 47 to 49 micrograms/ml for both antibiotics. Ceftriaxone displayed the longest t1/2 (7.65 h) and the highest C1h (137.8 micrograms/ml), while we observed the shortest t1/2 (1.05 h) and the lowest C1h (19.85 micrograms/ml) with imipenem. At 1 h, cefpirome and, even more so, imipenem showed significantly better serum bactericidal activities against S. aureus (1:273 and 1:80) than did the other antibiotics (P less than 0.0005; analysis of variance with randomized block design and Bonferroni correction). Against E. cloacae, we observed the highest serum bactericidal titers at 1 h with cefpirome, and this superiority vis-à-vis the other antibiotics tested was maintained for up to 8 h after dosing. Ceftazidime remained the most active agent tested against P. aeruginosa (serum bactericidal activity titers, 1:43 at 1 h) up to 8 h. In summary, the study showed that cefpirome and imipenem provide more potent serum bactericidal activities than do broad-spectrum cephalosporins against S. aureus; thus, both of these antibiotics should be adequate against serious S. aureus infections. In addition, cefpirome appears to be a promising alternative for treatment of infections caused by E. cloacae and P. aeruginosa.     

Presence of mixed colony-forming cells in long-term hamster bone marrow suspension cultures: response to pokeweed spleen conditioned medium

In contrast to the murine system, long-term hamster bone marrow suspension cultures maintain proliferation of both pluripotent and committed stem cells in the absence of an adherent layer and without addition of exogenous factors, such as hydrocortisone. Addition of pokeweed-mitogen-stimulated hamster spleen conditioned medium (SCM) to these long-term suspension cultures produces an increase in the number of mixed colonies assayed in soft-agar, These mixed colonies, which contained four cell lineages--granulocytic, erythroid, megakaryocytic, and macrophage--could be generated from cells grown in suspension for over 6 mo. Addition of SCM also induces an initial rapid expansion of the myeloid compartment, and this expansion results in 70% of the cells being terminally differentiated granulocytes. In contrast, addition of SCM to hamster bone marrow cultures containing both adherent cells and hematopoietic stem cells produced no change in the number of mixed colonies generated in the culture. This system allows the in vitro study of the process of stem cell proliferation and differentiation and also provides a means to examine the relationship of adherent and supernatant bone marrow populations.     

Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors

Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.     

Producing desired ice faces

The ability to prepare single-crystal faces has become central to developing and testing models for chemistry at interfaces, spectacularly demonstrated by heterogeneous catalysis and nanoscience. This ability has been hampered for hexagonal ice, I_h––a fundamental hydrogen-bonded surface––due to two characteristics of ice: ice does not readily cleave along a crystal lattice plane and properties of ice grown on a substrate can differ significantly from those of neat ice. This work describes laboratory-based methods both to determine the I_h crystal lattice orientation relative to a surface and to use that orientation to prepare any desired face. The work builds on previous results attaining nearly 100% yield of high-quality, single-crystal boules. With these methods, researchers can prepare authentic, single-crystal ice surfaces for numerous studies including uptake measurements, surface reactivity, and catalytic activity of this ubiquitous, fundamental solid.Studies of model, single-crystal surfaces have revolutionized understanding of a vast array of heterogeneous catalysts and nanoparticles ranging from pure metals to alloys to semiconductors. Applying the single-crystal surface strategy to ice––arguably one of the most fundamental and ubiquitous hydrogen-bonded interfaces––has been limited due to challenges associated with surface generation. As a result, questions about molecular-level dynamics, surface binding site patterns, and the molecular-level structure remain unanswered (1). Several strategies have been adopted for studying ice: (i) Depositing solid water on a metal or ionic substrate that matches the oxygen lattice (2, 3). However, ice on a substrate often has distinctly different properties from those of neat ice; indeed, such ice can even be hydrophobic (4, 5)! (ii) Uptake measurements often use a Knudsen cell with vapor-deposited ice on a substrate (6) or compacted, finely divided, artificial snow (7) to arrive at a molecular-level picture for gas–particle interaction despite the irregular, highly variable surfaces used. (iii) Small crystallites can be well characterized but, as highlighted by Libbrecht and Rickerby (8), results can be clouded by competition from nearby crystallites; small faces compete with adjacent faces. In addition, crystallites are perturbed by the supporting surface. It is therefore desirable to prepare macroscopic samples with known faces.Interactions at ice surfaces have a particularly profound effect on climate. For example, correlational studies suggest that rain formation depends on ice particles in clouds (9), but not all ice-containing clouds yield rain. It is thought that variation in supersaturation and the mechanism for gathering water molecules by ice particles profoundly affects precipitation. Discrepancies between experiment and theory are often rationalized as a result of irregular shapes, inelastic scattering, or differing binding sites leaving large uncertainties for climate models (10). More reproducible, well-characterized surfaces of I_h––the most stable form of ice at ambient pressure––are needed to bring clarity.Ice is unusual in that the macroscopic sample does not reveal the crystal lattice orientation. Neighboring grain lattice orientation is a critical issue in the ice-core and glaciology communities (11). Hence, previous work (12–14) focused on determining grain orientation with respect to the grain boundary. The most quantitative of these are the two methods of Matsuda (12). The first uses etch pits measuring lengths inside the pit. Large uncertainties in length measurements result in large uncertainties in lattice axis orientation angles; this is not a major issue for grain growth studies but is a serious problem for generating targeted faces. The second method measures only the azimuths, thus incompletely determining orientation. Both methods break down if the optic axis is near-parallel to the surface, and neither provides the tools required to accurately orient a macroscopic sample to generate a targeted face. Lattice orientation could be determined with X-ray methods (15, 16) provided such determination includes a connection to the macroscopic sample. For wide-spread use, a laboratory-based method is preferable. This work describes two methods to fill this important need. The first uses pit perimeter ratio measurements; because the perimeter is sharp, accuracy is greatly improved. The second method locates the optic axis via cross-polarizers (11, 17), then precisely determines the hexagonal orientation via etching. Closed-form, analytical formulas are derived relating lattice orientation to the macroscopic sample. These orientation formulas feed into rotation matrices generating additional analytical formulas enabling precise cutting of any targeted face. The result is illustrated by cutting each of the three major ice faces. These techniques provide researchers with the tools needed to prepare neat ice surfaces.This work specifically describes face preparation from cylindrical boules (18); however, the method is easily adapted to any macroscopic, single-crystal geometry. Due to nearly equal energy faces, ice takes on the shape of the confining container. The near-energy match is demonstrated by growth in the modified Bridgeman apparatus (19). Nucleation occurs on a polycrystalline seed; single-crystal growth is achieved due to competitive growth among the multiple ice–water interfaces (18). Careful thermal management maintains near-equilibrium conditions yielding a large single crystal, but the crystal orientation is not a priori known. [Note: ice seeded by a floating crystal tends to have the optic axis perpendicular to the growth direction but single-crystal yield is low, ~10% (20).] Close energy match among the faces also means that ice does not readily cleave along any lattice plane (21). Thus, successful face preparation for any ice sample begins with characterization of the lattice orientation.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.     

Nonhomogeneous distribution of leukemia in the bone marrow during minimal residual disease

In a rat model (BNML) for human acute myelocytic leukemia the distribution of leukemic cells in bone marrow samples from various sites was investigated, using monoclonal antibodies (MoAbs) and flow cytometry. Rats were studied before chemotherapy as well as thereafter, ie, in the "minimal residual disease" (MRD) phase. Bone marrow from different types of bones was analyzed from each animal. Before treatment, the ratio of the measured extreme values (ie, highest/lowest value) for leukemic cell frequencies in bones from individual rats ranged from 3.7 to 11.7. During the MRD phase the ratios of the extremes ranged from a factor of 36 to more than 13,000 from one rat to another. The variability between bones of comparable size was estimated by studying the ribs from each individual animal. Within individuals the extremes differed by a factor of 1.2 to 4.0 before chemotherapy and from 2.4 to greater than 320 after chemotherapy. The variability within the marrow cavity of a single bone was determined by analyzing multiple samples from femoral bones cut into slices. The leukemic cell frequency appeared to vary considerably, ie, before treatment from 1.7 to 7.3 and during MRD from 4 to 28,000. The presented data may contribute to understanding the sometimes conflicting observations in leukemic patients. Improvement of methods for detecting MRD will not automatically lead to a more accurate estimation of the total tumor burden. The reliability of diagnoses based on the analysis of single bone marrow aspirates appears to be highly questionable.     

High-level expression and purification of a recombinant human erythropoietin produced using a baculovirus vector

Conditions presently have been established for the high-level expression and simplified purification of recombinant human erythropoietin produced in Spodoptera frugiperda cells. Expression, as mediated by infection with a recombinant baculovirus, was accomplished in suspension culture using reduced levels of serum and media supplements experimentally determined to provide optimum levels of factor production (500,000 U/L). Purification of this recombinant human erythropoietin to virtual homogeneity (greater than or equal to 99%) was accomplished via a simple three-step procedure involving isocratic elution from DEAE-Sephacel, reverse-phase high performance liquid chromatography (HPLC) on a C4 medium, and the single-step elution of purified hormone from concanavalin A agarose. Overall, an 890-fold purification was accomplished with a recovery of 80% as assayed in vitro. Biologically, this purified erythropoietin is highly active, possessing a specific activity in vitro of 200,000 U/mg protein. Chemically, this erythropoietin (molecular weight [mol wt] 26,200) appears exceptionally uniform in its oligosaccharide constitution (30%) as contrasted with heterogeneously glycosylated erythropoietins derived from mammalian cells (mol wt 30,000 to 38,000; 40% to 50% complex-type oligosaccharide). Thus, human erythropoietin as presently produced in an insect cell line comprises not only an abundant source of highly active, readily purified hormone for studies of its mechanism of action and cell surface receptor, but also represents a uniquely homogeneous form that should prove advantageous for direct structural analyses.