[HIV infection in the intensive care unit]. / Die HIV-Infektion auf der Intensivstation.

Around 88,000 people in Germany live with an HIV (human immunodeficiency virus) infection. The proportion of those over 50 is around 30% and it has now become more likely that an older HIV-positive patient with other pre-existing illnesses will have to be treated in an intensive care unit (ICU) for a reason not directly associated with HIV than a person with a new HIV diagnosis for acquired immune deficiency syndrome (AIDS). Nevertheless, one third of patients with a new HIV diagnosis already have an advanced immune deficiency. Neurological or respiratory symptoms that require intensive medical care must be expected in these patients. The present article aims to raise awareness of these clinical pictures and the necessary differential diagnostics, and to provide the reader with an overview of the most important opportunistic infections and their treatment. In addition, the main focus of this article is on the possibilities of antiretroviral therapy in intensive care patients and provides the clinician with an overview of the start of treatment, the selection of suitable substances, and their dosage in the ICU.

Calcite incorporated in silica/collagen xerogels mediates calcium release and enhances osteoblast proliferation and differentiation.

Multiphasic silica/collagen xerogels are biomaterials designed for bone regeneration. Biphasic silica/collagen xerogels (B30) and triphasic xerogels (B30H20 or B30CK20) additionally containing hydroxyapatite or calcite were demonstrated to exhibit several structural levels. On the first level, low fibrillar collagen serves as template for silica nanoparticle agglomerates. On second level, this silica-enriched matrix phase is fiber-reinforced by collagen fibrils. In case of hydroxyapatite incorporation in B30H20, resulting xerogels exhibit a hydroxyapatite-enriched phase consisting of hydroxyapatite particle agglomerates next to silica and low fibrillar collagen. Calcite in B30CK20 is incorporated as single non-agglomerated crystal into the silica/collagen matrix phase with embedded collagen fibrils. Both the structure of multiphasic xerogels and the manner of hydroxyapatite or calcite incorporation have an influence on the release of calcium from the xerogels. B30CK20 released a significantly higher amount of calcium into a calcium-free solution over a three-week period than B30H20. In calcium containing incubation media, all xerogels caused a decrease in calcium concentration as a result of their bioactivity, which was superimposed by the calcium release for B30CK20 and B30H20. Proliferation of human bone marrow stromal cells in direct contact to the materials was enhanced on B30CK20 compared to cells on both plain B30 and B30H20.

Manipulation of osteoclastogenesis: Bioactive multiphasic silica/collagen composites and their effects of surface and degradation products.

The intent of the present study was to demonstrate that multiphasic silica/collagen xerogels are able to manipulate cellular processes. These xerogels were prepared by a sol-gel approach allowing the incorporation of mineral phases. The resulting nanocomposites are designed as biomaterial for bone regeneration. Human osteoclasts derived from peripheral blood mononuclear cells were cultured both indirectly and directly, either in presence of different xerogel types or on their surface, to investigate the factor with the main influence on osteoclastogenesis. To this end, the incorporation of a third phase to silica/collagen xerogels was used to affect osteoclastogenesis. In cell culture, ambient ion conditions controlled by both the degradation products of the xerogel and the bioactivity-dependent ion release and reprecipitation were shown to have the main effect on osteoclast specific enzyme tartrate-resistant acid phosphatase (TRAP) 5b. Late stage of osteoclastogenesis characterized by resorption was strongly dependent on the xerogels composition. Surface chemistry of the xerogels was displayed to play an important role in osteoclast resorption. Biphasic silica/collagen xerogels and triphasic xerogels with calcium carbonate offered widespread resorbed areas, whereas hydroxyapatite containing xerogels showed distinctly reduced resorption. The incorporation of strontium carbonate and phosphate, respectively, as third phase changed TRAP 5b activity dose-dependently and inhibited resorption within 21 days. Quantitative evaluation on osteoclast differentiation was carried out using biochemical methods (TRAP 5b, cathepsin K) and was supported by confocal laser scanning microscopy and scanning electron microscopy (SEM). Qualitative estimation of resorption was carried out by SEM.

Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir (DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis of the literature on dual treatment strategies using protease inhibitors in combination with an NRTI.

BACKGROUND: Here, we report the case of an HIV positive patient under a dual antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir with stable clinical, virological, and immunological response over 126 weeks. Dual antiretroviral therapy has the advantage of reduced toxicity and lower health care costs, treatment failure and fostering drug resistance are perceived risks. Optimal drug combinations and indication criteria for dual treatment remain controversial. Nevertheless, first clinical trials indicate non-inferiority for combinations of nucleoside reverse transcriptase inhibitors and protease inhibitors. This case presents the combination of tenofovir disoproxil in combination with a protease inhibitor as a new potential dual treatment regimen. METHOD: We performed a systematic literature search and meta-analysis of trials comparing dual to triple ART. RESULTS: Literature review revealed nine studies in which dual therapy with a protease inhibitor and an NRTI was compared to triple therapy. We performed a meta-analysis of six trials that reported a 48-week follow-up. In treatment-naïve patients as well when ART switch was assessed, there was no difference in the treatment success in patients with dual ART versus triple. CONCLUSION: We conclude that dual therapy with a protease inhibitor and NRTI is safe and effective. The use of tenofovir in dual treatment as described in our case needs to be assessed in future clinical trials.

Prevalence and molecular diversity of invasive Streptococcus dysgalactiae and Streptococcus pyogenes in a German tertiary care medical centre.

Prevalence of invasive ß-haemolytic streptococci (BHS) at a tertiary care hospital and molecular diversity of S. pyogenes and S. dysgalactiae was studied. Between 2012 and 2016, all blood culture sets (n = 55,839), CSF (n = 8413) and soft tissue (n = 20,926) samples were analysed for BHS positivity using HYBASE software. Molecular profiles of 99 S. pyogenes and S. dysgalactiae were identified by sequencing of M protein genes (emm types) and multiplex PCR typing of 20 other virulence determinants. Streptococci contributed to 6.2% of blood, 10.7% of CSF and 14.5% of soft tissue isolates, being among the most common invasive isolates. The overall rates of invasive S. pyogenes, S. agalactiae, S. dysgalactiae and S. pneumoniae were 2.4, 4.4, 2.1, and 5.3%. Whereas S. pneumoniae was 1.5% more common in CSF samples, BHS isolates were 2-fold and 11-fold higher in bacteraemia and invasive soft tissue infections. Genetic BHS typing revealed wide molecular diversity of invasive and noninvasive group A and group G BHS, whereas one emm-type (stG62647.0) and no other virulence determinants except scpA were detected in invasive group C BHS. BHS were important invasive pathogens, outpacing S. pneumoniae in bacteraemia and invasive soft tissue infections. The incidence of S. dysgalactiae infections was comparable to that of S. pyogenes even with less diversity of molecular virulence. The results of this study emphasise the need for awareness of BHS invasiveness in humans and the need to develop BHS prevention strategies.

Pressure-Induced Ferromagnetism due to an Anisotropic Electronic Topological Transition in Fe_{1.08}Te.

A rapid and anisotropic modification of the Fermi-surface shape can be associated with abrupt changes in crystalline lattice geometry or in the magnetic state of a material. We show that such an electronic topological transition is at the basis of the formation of an unusual pressure-induced tetragonal ferromagnetic phase in Fe_{1.08}Te. Around 2 GPa, the orthorhombic and incommensurate antiferromagnetic ground state of Fe_{1.08}Te is transformed upon increasing pressure into a tetragonal ferromagnetic state via a conventional first-order transition. On the other hand, an isostructural transition takes place from the paramagnetic high-temperature state into the ferromagnetic phase as a rare case of a "type-0" transformation with anisotropic properties. Electronic-structure calculations in combination with electrical resistivity, magnetization, and x-ray diffraction experiments show that the electronic system of Fe_{1.08}Te is instable with respect to profound topological transitions that can drive fundamental changes of the lattice anisotropy and the associated magnetic order.

Additional energy scale in SmB6 at low-temperature.

Topological insulators give rise to exquisite electronic properties because of their spin-momentum locked Dirac-cone-like band structure. Recently, it has been suggested that the required opposite parities between valence and conduction band along with strong spin-orbit coupling can be realized in correlated materials. Particularly, SmB6 has been proposed as candidate material for a topological Kondo insulator. Here we observe, by utilizing scanning tunnelling microscopy and spectroscopy down to 0.35 K, several states within the hybridization gap of about ±20 meV on well characterized (001) surfaces of SmB6. The spectroscopic response to impurities and magnetic fields allows to distinguish between dominating bulk and surface contributions to these states. The surface contributions develop particularly strongly below about 7 K, which can be understood in terms of a suppressed Kondo effect at the surface. Our high-resolution data provide insight into the electronic structure of SmB6, which reconciles many current discrepancies on this compound.

Solitonic Spin-Liquid State Due to the Violation of the Lifshitz Condition in Fe(1+y)Te.

A combination of phenomenological analysis and Mössbauer spectroscopy experiments on the tetragonal Fe(1+y)Te system indicates that the magnetic ordering transition in compounds with higher Fe excess, y≥0.11, is unconventional. Experimentally, a liquidlike magnetic precursor with quasistatic spin order is found from significantly broadened Mössbauer spectra at temperatures above the antiferromagnetic transition. The incommensurate spin-density wave order in Fe(1+y)Te is described by a magnetic free energy that violates the weak Lifshitz condition in the Landau theory of second-order transitions. The presence of multiple Lifshitz invariants provides the mechanism to create multidimensional, twisted, and modulated solitonic phases.

Interplay of structure, magnetism, and superconductivity in Se substituted iron telluride with excess Fe.

We investigated the evolution of the temperature-composition phase diagram of Fe(1+y)Te upon Se substitution. In particular, the effect of Se substitution on the two-step, coupled magneto-structural transition in Fe(1+y)Te single crystals is investigated. To this end, the nominal Fe excess was kept at y = 0.12. For low Se concentrations, the two magneto-structural transitions displayed a tendency to merge. In spite of the high Fe-content, superconductivity emerges for Se concentrations x ⩾ 0.1. We present a temperature-composition phase diagram to demonstrate the interplay of structure, magnetism and superconductivity in these ternary Fe-chalcogenides.

Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 µm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 µm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 µm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

Properties of injectable ready-to-use calcium phosphate cement based on water-immiscible liquid.

Calcium phosphate cements (CPCs) are highly valuable materials for filling bone defects and bone augmentation by minimal invasive application via percutaneous injection. In the present study some key features were significantly improved by developing a novel injectable ready-to-use calcium phosphate cement based on water-immiscible carrier liquids. A combination of two surfactants was identified to facilitate the targeted discontinuous exchange of the liquid for water after contact with aqueous solutions, enabling the setting reaction to take place at distinct ratios of cement components to water. This prolonged the shelf life of the pre-mixed paste and enhanced reproducibility during application and setting reactions. The developed paste technology is applicable for different CPC formulations. Evaluations were performed for the formulation of an α-TCP-based CPC as a representative example for the preparation of injectable pastes with a powder-to-carrier liquid ratio of up to 85:15. We demonstrate that the resulting material retains the desirable properties of conventional CPC counterparts for fast setting, mechanical strength and biocompatibility, shows improved cohesion and will most probably show a similar degree of resorbability due to identical mineral structure of the set products.

Memory effect in Dy0.5Sr0.5MnO3 single crystals.

We have performed a series of magnetic aging experiments on single crystals of Dy(0.5)Sr(0.5)MnO(3). The results demonstrate striking memory and chaos-like effects in this insulating half-doped perovskite manganite and suggest the existence of strong magnetic relaxation mechanisms of a clustered magnetic state. The spin-glass-like state established below a temperature T(sg)≈ 34 K originates from quenched disorder arising due to the ionic-radii mismatch at the rare earth site. However, deviations from the typical behavior seen in canonical spin glass materials are observed which indicate that the glassy magnetic properties are due to cooperative and frustrated dynamics in a heterogeneous or clustered magnetic state. In particular, the microscopic spin flip time obtained from dynamical scaling near the spin glass freezing temperature is four orders of magnitude larger than microscopic times found in atomic spin glasses. The magnetic viscosity deduced from the time dependence of the zero-field-cooled magnetization exhibits a peak at a temperature T < T(sg) and displays a marked dependence on waiting time in zero field.

Phase transitions and rare-earth magnetism in hexagonal and orthorhombic DyMnO(3) single crystals.

The floating-zone method with different growth ambiences has been used to selectively obtain hexagonal or orthorhombic DyMnO(3) single crystals. The crystals were characterized by x-ray powder diffraction of ground specimens and a structure refinement as well as electron diffraction. We report magnetic susceptibility, magnetization and specific heat studies of this multiferroic compound in both the hexagonal and the orthorhombic structure. The hexagonal DyMnO(3) shows magnetic ordering of Mn(3+) (S = 2) spins on a triangular Mn lattice at T(N)(Mn) = 57 K characterized by a cusp in the specific heat. This transition is not apparent in the magnetic susceptibility due to the frustration on the Mn triangular lattice and the dominating paramagnetic susceptibility of the Dy(3+) (S = 9/2) spins. At T(N)(Dy) = 3 K, a partial antiferromagnetic order of Dy moments has been observed. In comparison, the magnetic data for orthorhombic DyMnO(3) display three transitions. The data broadly agree with results from earlier neutron diffraction experiments, which allows for the following assignment: a transition from an incommensurate antiferromagnetic ordering of Mn(3+) spins at T(N)(Mn) = 39 K, a lock-in transition at T(lock-in) = 16 K and a second antiferromagnetic transition at T(N)(Dy) = 5 K due to the ordering of Dy moments. Both the hexagonal and the orthorhombic crystals show magnetic anisotropy and complex magnetic properties due to 4f-4f and 4f-3d couplings.

Investigations on the spin-glass state in Dy(0.5)Sr(0.5)MnO(3) single crystals through structural, magnetic and thermal properties.

Single crystals of Dy(0.5)Sr(0.5)MnO(3) are grown using the optical floating zone technique, and their structural, magnetic, transport and thermal properties have been investigated. Magnetization measurements under field-cooled and zero-field-cooled conditions display irreversibility below 35 K. The magnetization does not saturate up to fields of 5 T in the temperature range 5-350 K. AC susceptibility shows a cusp around 32 K that shifts to higher temperature with increasing frequency. This frequency dependence of the peak temperature follows a critical slowing down with exponent zν = 3.6. Electrical resistivity shows insulating behavior, and the application of magnetic fields up to 10 T does not change this qualitative behavior. However, a marked negative magnetoresistance is observed in the paramagnetic phase reaching 80% at 70 K and 10 T. The observed resistivity behavior does not obey an activated type of conduction. These features are characteristic of spin-glass behavior in this half-doped insulating manganite. It is argued that the spin-glass-like state originates from the A-site disorder, which in turn results from the random distribution of cations with different ionic radii. Specific-heat measurements reveal a sizable linear contribution at low temperature that may be associated with the glassy magnetic ordering and a Schottky-like anomaly in a wide temperature range between 8 and 40 K. The distribution of Schottky levels is explained by the inhomogeneity of the molecular field in the spin-glass state that leads to variable splitting of the Kramers ground-state doublets in Dy(3+).

Electrochemically assisted deposition of thin calcium phosphate coatings at near-physiological pH and temperature.

An electrochemical method for the deposition of calcium phosphate phases on titanium surfaces using the galvanostatic mode is presented. Deposition was performed in a (Ca(2+) / H(x)PO(4) ((3-x)-))-containing electrolyte near physiological conditions with regard to pH (6.4) and temperature (36 degrees C). Cathodic alkalization leads first to the formation of a thin homogeneous layer that shows a nanoscale surface topography of alternating wall-like elevations and channels. It is thought that these channels in the calcium phosphate prelayer are formed as pathways for hydroxyl ions and hydrogen. Upon this layer, spheres of amorphous calcium phosphate (ACP) are formed as indicated by Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy. According to transmission electron microscopy images, these spheres consist of small clusters of calcium phosphate (approximately 30 nm) and can grow up to 300 nm in diameter. Characteristic for this ACP is a high water content as seen by FTIR. As a function of current density, the ACP is then transformed into crystalline hydroxyapatite (HAP), which was identified using FTIR and X-ray diffraction. The morphology of the HAP crystals can be described as needles with dimensions of <500-nm length and <60-nm width. By choice of different electrochemical parameters, a homogeneous coating of either ACP, HAP, or the intermediate phase can be achieved, as shown in a kinetic phase diagram, thus allowing the formation of coatings with different properties in solubility and morphology.

Electrochemical behavior of titanium-based materials - are there relations to biocompatibility?

For biomedical applications the physico-chemical properties of oxide layers, always present in titanium-based materials, are of special interest because the biological system is in direct contact only with these oxides. Using electrochemical impedance spectroscopy and galvanostatic polarization it is shown that the different compositions of c.p.-titanium, Ti6Al4V, and Ti6Al7Nb result in different physico-chemical properties of air formed passive layers and anodic oxide layers. This may have a direct impact on the biocompatibility of these materials. Results of impedance spectroscopy distinctly differ in the flatband potentials as well as in the donor densities of air-formed passive layers with Ti6Al7Nb showing an approximately 50% smaller donor density than the other materials. Anodic galvanostatic polarization results in voltage-charge density curves with distinct differences in the Faraday efficiency epsilon of the oxide formation between Ti6Al7Nb and c.p.-titanium/Ti6Al4V, especially for low current densities. These effects correlate strongly with the donor densities in the air formed passive films of the examined materials. SEM-images of anodic oxide layers show a blister containing surface morphology of the outer part of the oxide layers for all materials. This morphology is probably caused by oxygen evolution, a process which relies on the transfer of electrons through the growing anodic oxide layers and strongly depends on the donor density in the air formed passive layers. Again, the much more pronounced morphology on c.p. titanium/Ti6Al4V agrees with the different donor densities in the air formed passive layers on the materials. These findings correlate with the good biocompatibility of Ti6Al7Nb and suggest that conduction mechanisms, in air formed passive layers and anodic oxide layers, contribute to processes that determine the biocompatibility of these materials.

[Videotape preparation of patients before hip replacement surgery improves mobility after three months]. / Video-Vorbereitung bei Hüftgelenkersatz-Operation verbessert die Mobilität nach drei Monaten.

Long-term follow-up investigations of the effect of psychological preparation on postoperative physical outcome measures have very rarely been done. In this study a three-month follow-up of a previous investigation of videotape preparation before hip replacement surgery is reported. 100 patients who previously participated in a randomized controlled study received physical examination and x-ray of the hip joint three months after the operation. The mobility of the replaced hip joint was recorded as well as ossifications of the joint. Prepared patients showed a significantly higher improvement of internal rotation, rotational range of motion, and abduction, compared to the controls. The effect sizes ranged between 21% and 32% and, thus, were of clinical relevance. Prepared patients showed less ossifications (15%) that controls (22%), this difference was not significant. For the first time it could be demonstrated that psychological preparation before surgery can not only improve short-term and psychosocial outcome parameters, but also long-term physical measures. The reason for this effect remains to be investigated.

Influence of sympathetic nervous system on dexamethasone-stimulated renal tubular transport of p-aminohippurate in young rats.

After simultaneous administration of dexamethasone together with 6-hydroxydopamine or adrenergic neuronal blocking agents (alpha-methyldopa, reserpine, guanethidine) the dexamethasone-stimulated increase in renal excretion of p-aminohippurate (PAH) is distinctly diminished. The same is true for dopamine. This depressive effect could be proved by measurement of transport rates of PAH in renal cortical slices in vitro. The increase in kidney weight and in the protein content of kidney tissue in dexamethasone-treated rats is lower in rats simultaneously treated with adrenergic neuronal blocking agents of 6-hydroxydopamine. Adrenoceptor agonists and antagonists (pholedrine, orciprenaline, phentolamine, propranolol) are without influence on the dexamethasone-stimulated increase in PAH transport.