[Community-based rehabilitation and outpatient care for patients with acquired brain injury and chronic neurological disability in Germany: continuing support for social participation and re-integration in the neurological care system?]. / Die neurologische Rehabilitations-Phase E: Nachgehende Leistungen zur sozialen (Re-)Integration und Teilhabe - ein Kontinuum?

In Germany a number of patients who are suffering from acquired brain injury and chronic neurological disability are either undersupplied or exposed to inappropriate care in their social environment. The number of these patients is increasing due to the changes in the procedures of care and due to demographic factors. While acute medical care and early rehabilitative treatment is accessible throughout the German health care system the necessary multimodal and competent care is rare or absent in the social participative sites such as life and occupational environments of the patients. The complex impairment of the brain, the central organ for sensorial, executive and other cognitive functions of human beings, renders the affected patient an exception in the system of medical and social care - this has only inadequately been considered in the past. The authors explain the necessity to disclose the status of a "human-with acquired-brain damage (Mensch-mit-erworbener-Hirnschädigung, MeH)" explicitly as severely disabled. The paper recommends a number of structural and procedural elements that have proven to overcome the insufficient or inappropriate support in integrating the patients suffering from acquired brain injury and chronic neurological disability in their social environment as well as for a demand-focused support with sustainable rehabilitative and ambulant follow-up procedures. Comparisons with other developed health care systems and international guidelines show that with organizing of early-supported-discharge, community-ambulation, shared-care and community-based-rehabilitation these problems have long since been identified elsewhere. Community-based and resident-oriented concepts have already been systematically implemented. In order to achieve the necessary support for the individual patient, a nation-wide development is necessary in Germany to perform the principles of the German social code and the principles of the Convention on the Rights of Persons with Disabilities of the United Nations: Goals of rehabilitation have to be more than functional treatment. Activation of the patient and supporting their coping and adaptive processes are necessary to achieve social participation and (re)integration into the community and in occupational life as implied by the standards of our society. Important elements of these are (1) identification of the individual patient and his/her burden during acute phase treatment or early rehabilitation (defined red-flag), (2) an individual clinical reasoning and planning of interventions and help, (3) general acceptance of the defined demands by all "players" in medical and social networks, (4) coordination and supervision of the medical and social interventions and of the assistive processes necessary in the individual environment. What seems to be needed is (5) systematic orientation to the goal of individual social participation at all levels of support, (6) cross linking, cooperation and development of the existing medical and social structures on site, (7) expansion of the legal framework and (7a) especially control of the implementation of the existing rights of social benefits and (7b) surveillance (transparency and quality management not only in the area of caregivers but also for the administration of social insurances!). The recommendations of the authors integrate systematically into the phase model of neurorehabilitation (VDR/BAR) in Germany. The focus of this work is the needs-appropriate programming of phase E, i. e., the transition between inpatient and outpatient care, between the clinical facility-oriented and the community-based (domicile-oriented, occupational-oriented) sectors, between welfare and independency.

Interaction of genistein benzyl derivatives with lipid bilayers--fluorescence spectroscopic and calorimetric study.

The purpose of the present paper was to assess the ability of genistein benzyl derivatives to interact with lipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of chemical structure, the studied compounds penetrated bilayers and affected their polar as well as hydrophobic regions. It was also found that physical state of bilayer played some role in flavonoid-lipid interactions.

Two methods for direct ortho-arylation of benzoic acids.

Two new palladium-catalyzed methods for the direct ortho-arylation of free benzoic acids have been developed. The first method employs stoichiometric silver acetate for iodide removal, aryl iodide as the coupling partner, and acetic acid solvent. This method is applicable to the arylation of electron-rich to moderately electron-poor benzoic acids and tolerates chloride and bromide substituents on both coupling partners. The second method involves the use of aryl chloride, cesium carbonate base, n-butyl-di-1-adamantylphosphine ligand, and DMF solvent and is suitable for both electron-rich and electron-poor benzoic acids. Mechanistic studies of the second method point to the heterolytic C-H bond cleavage as the rate-determining step.

Palladium-catalyzed arylation of electron-rich heterocycles with aryl chlorides.

[reaction: see text] Palladium-catalyzed C-H activation: cheap aryl chlorides can now be used for the arylation of a wide variety of electron-rich heterocycles. The key to the success of this reaction is the use of a bulky, electron-rich phosphine ligand. No copper additives are needed.

Interactions of phenothiazines with lipid bilayer and their role in multidrug resistance reversal.

The mechanism of multidrug resistance (MDR) reversal is not fully understood yet. Interaction of MDR modifiers with lipid bilayer of cell membranes and alterations of fluidity or other biophysical properties of plasma membrane might be an important factor in mechanism of MDR modulation and reversal. In this review we focus on phenothiazines which belong to the group of drugs known to modify MDR in different types of cells, from cancer cells up to various kinds of microorganisms. First, the aggregation properties of phenothiazines and their interactions with lipid bilayers are described. The localization of phenothazine derivative molecules in bilayers and alteration of membrane properties are discussed. Apart from the influence on model bilayers also the interactions of phenothiazines with cellular membranes (especially of erythrocytes) are reviewed. In subsequent sections the anti-MDR activity of phenothiazine derivatives observed in microorganisms and in cancer cells is described. The possible molecular mechanisms involved in MDR reversal by these compounds are presented. The direct interactions of phenothiazines with multidrug transporters and other effects of these modulators on plasma membranes are discussed. Finally, the structural features of phenothiazine derivatives essential for their optimal MDR reversal activity are described.

Lipids as a target for drugs modulating multidrug resistance of cancer cells.

In this review we focus on the role of the membrane lipids in multidrug resistance and its modulation. Results of the research performed in recent years indicate the importance of lipid phase playing active role in many membrane processes. Along with the alterations of lipid membrane composition of cancer cells (with respect to the normal ones) the resulting changes of the biophysical membrane properties are discussed. Next we describe the general features of multidrug resistance phenomenon paying a special attention to the role of lipids and alterations of lipid membrane composition in MDR cells. Taking into account the phase separation properties of sphingolipids the importance of membrane heterogeneity (presence of caveole and lipid rafts) is emphasised. On the basis of vacuum cleaner hypothesis of drug transport proteins action we discuss the importance of lipid bilayer as medium in which diffusion of drugs takes place. Considering the membrane fluidity and its influence on the integral proteins activity, we underline the role of balance between the passive cellular influx and active efflux of the drug molecules. Finally the effects exerted on membranes by different kinds of multidrug resistance modulators (chemosensitizers) are described. In this part we discuss the influence of verapamil, phenothiazine derivatives, tamoxifen and chosen flavonoids on the biophysical properties of membrane lipids. Some further consequences of the alteration of membrane state are also considered.

Trifluoperazine induces domain formation in zwitterionic phosphatidylcholine but not in charged phosphatidylglycerol bilayers.

The interaction of trifluoperazine with the zwitterionic lipids dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine and with anionic dimyristoylphosphatidylglycerol was studied by means of microcalorimetry and fluorescence spectroscopy. Intercalation of drug molecules into the lipid bilayers was confirmed by the observed differential scanning calorimetry peak broadening and the decrease in chain-melting temperatures. For trifluoperazine:lipid mole ratios higher than 0.4 and 0.6 (for dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine, respectively) the deconvolution of transition profiles into two Gaussian components was possible, which suggests phase separation in the studied mixtures. Deconvolution of the thermograms was not possible for any of the drug:dimyristoylphosphatidylglycerol mole ratios studied. To confirm the existence of phase separation in trifluoperazine-phosphatidylcholine mixtures fluorescence spectroscopy experiments were performed using Laurdan as a probe. From the generalised polarisation versus excitation wavelength dependences, recorded at different temperatures, we conclude that a phase separation occurs in the gel state of the studied trifluoperazine-phosphatidylcholine mixtures. We attribute the existence of domains in the bilayer to the dissimilar interactions of two protonation forms of trifluoperazine with phosphatidylcholine molecules. Structural defects present at domain boundaries could be related to the trifluoperazine induced increase of membrane permeability and fluidity. This may partially explain the mechanism of multidrug resistance modulation by trifluoperazine.

After a merger: the dilemma of the best leadership approach for nursing.

The following case study exemplifies for the nurse leader some of the difficulties involved in making a merger work and selecting the best options to sustain nursing services following the merger. Three nurse leaders look at the case study from a variety of viewpoints and suggest a range of responses that gives the reader an opportunity to consider a selection of insights that best address the issues presented in the case study. All of the respondents have been involved in complex mergers and bring a depth of experience to their review of the case.

Hospital falls: development of a predictive model for clinical practice.

A retrospective case-control study related to falls was conducted at an 1,120-bed acute care tertiary hospital. The case (fall) sample consisted of 102 falls and 236 control (nonfall) charts during a 1-month period. An instrument developed by Hendrich (1988) was modified for use in the study. Demographic data and risk factors were recorded. Descriptive statistics included risk factor percentages for each sample and the corresponding univariate relative risks. Logistic regression was used to develop a multivariate risk factor model with seven risk factors. The significant risk factors were recent history of falls, depression, altered elimination patterns, dizziness or vertigo, primary cancer diagnosis, confusion, and altered mobility. The adjusted relative risks were converted to risk points to be used to assess a patient's level of fall risk. Within the data set, a sensitivity of 77% (79 of 102) and specificity of 72% (169 of 236) were calculated. The model was cross-validated in a 1987 data set with a sensitivity of 83% (59 of 71) and specificity of 66% (106 of 161).

Changes in serum catecholamine levels in patients who are brain dead.

Prospective blood samplings from 15 patients admitted with a Glasgow Coma Score of less than 7 were obtained to observe and compare epinephrine, norepinephrine, and dopamine serum levels in patients with brain injury before, after, and in the absence of brain death. Nine of the patients developed or were admitted after brain death. Wide variations in catecholamine blood levels over time were documented, and subgroup analysis precluded useful statistical comparison or inference of the data. The data are presented therefore as descriptive observations only. No apparent differences were noted between similarly injured patients in whom brain death did not develop and patients before brain death or between patients with penetrating versus nonpenetrating brain injury. Brain death was preceded by hypertension and corresponding elevations in serum catecholamine levels in one patient with complete data. Catecholamine levels appeared to fall after brain death in most patients. Only minimal changes in myocardial histology were present in three donor hearts, and the two transplanted hearts functioned satisfactorily. Serum catecholamine measurement or monitoring does not provide a precise method of determining potential injury to the donor heart before or after brain death. Other experimental data and clinical observation indicate that some hearts may be injured in the donor during the evolution of brain death. Pharmacologic intervention may prevent such injury in experimental animals but must be used before brain death is induced. Such interventions should be studied in selected human donors before brain death to determine whether cardiac function is improved in the donor or recipient.

Interactions of selected insect neuropeptides with synthetic lipids.

Interactions of the insect neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr), its [beta-cyclohexyl-(4-O-methyl)2]-L-alanine analog, and the leucopyrokinin [2-8]-fragment (Thr-Ser-Phe-Thr-Pro-Arg-Leu-NH2), with synthetic phospholipids (DPPC, DMPE, DMPG) were studied using the microcalorimetric method. Most pronounced changes of the lipid thermotropic behavior were observed with DMPG/leucopyrokinin [2-8]-fragment mixtures. Proctolin itself was less active with all the lipids studied. The results obtained suggest that the studied peptides interact with the head group region of lipid bilayer.

Effect of spectrin on structure properties of lipid bilayers formed from mixtures of phospholipids. Fluorescence and microcalorimetric studies.

Effect of spectrin from human erythrocytes on structure properties of lipid bilayers formed from a mixture of phosphatidylethanolamine/phosphatidylserine (PE/PS) and/or phosphatidylethanolamine/phosphatidylcholine (PE/PC) was studied with the use of fluorescence and microcalorimetric methods. Spectrin did not affect the order parameter of lipids in PE/PS vesicles. However, spectrin binding to liposomes did influence temperature, half-width and enthalpy of phase transitions in mixtures of dimyristoylphosphatidylethanolamine (DMPE) and dimyristoylphosphatidylcholine (DMPC), and this effect was dependent on DMPE to DMPC weight ratio. A change in miscibility of the components in the presence of spectrin was observed and it might be due to spectrin-PE interactions.

Hormonal changes in brain dead patients.

Thirty neurologically impaired (Glasgow Coma Score less than 7) patients were evaluated to determine if changes in serum levels of thyroid hormone, cortisol, insulin, or lactate suggest that replacement therapy is needed before removal of organs for donation. Serum levels of free thyroxine (fT4), thyroid-stimulating hormone (TSH), reverse T3 (rT3), cortisol, insulin, and lactate were monitored in 16 patients before and after brain death and in 14 additional patients who were similarly compromised but did not become brain dead. Low fT3, normal fT4, and normal or high rT3 as found in most patients were consistent with a variant of the euthyroid sick syndrome although TSH was elevated in some patients. Cortisol, insulin, and lactate levels were also normal or high. No correlation was found between low thyroid hormones and elevated lactate or the amount of vasopressor needed to sustain BP. No significant changes occurred in hormone or lactate levels after brain death. The explanation for an elevated lactate remains unclear but we do not believe this single finding justifies the diagnosis of a hypothyroid state in these patients or the administration of thyroid hormone to brain dead organ donors.

The role of group structure in the action of some morpholinium chloride derivatives on model systems.

Effects of morpholinium chlorides, which exhibit fungicidal activity, on model lipid systems is discussed. It was shown by means of DSC and BLM techniques that for different salts possessing alkyl chains of identical length, the interaction with lipids depends strongly on the polar head charge and the structure of the salt. The results obtained and conclusions drawn can be useful in explaining the possible mechanism of the biological effectiveness of the compounds tested; this is suggested by the observation that salts tested showed the same sequence of activity in both biological tests and model experiments.