Comparative effectiveness of plasma-derived and recombinant FVIII concentrates in the on-demand and prophylactic treatment of patients with haemophilia A.
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Biomedical subjects
Publications and source records attributed to H Richter.
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BACKGROUND: The sun protection factor (SPF) of sunscreens is determined after application of a standard amount. The European Cosmetic Toiletry and Perfumery Association (COLIPA) standard amount is 2 mg/cm(2). Real-life application of sunscreen is probably less than this. AIM: To determine the amount of sunscreen present on the skin of people at the beach. METHODS: Volunteers at the beach were selected randomly and were not aware of being tested for the adequacy of their sunscreen application. All volunteers had applied sunscreen. Application had been more than 30 min before testing (sometimes up to 4 h earlier). The amounts of sunscreen applied to different body sites were determined quantitatively by tape stripping. Actual amounts of sunscreen applied were compared with the COLIPA standard. Also, sunscreen containing a fluorescent dye was applied to the skin of volunteers in a laboratory setting. The distribution of sunscreen application was visualized by UVA photography in a darkened room. RESULTS: Sixty volunteers, 33 males and 27 females, aged 17-68 years (median 32 years), were recruited at the beach. Sunscreen coverage was inadequate at all body sites. Coverage at various body sites differed greatly. Most volunteers had applied 10% or less of the COLIPA standard amount to all body sites assessed. The best protected areas were the upper arm and décolleté but, even in these areas, most volunteers had only applied 10% of the COLIPA standard amount. The worst protected areas were the ears and top of the feet. The back was typically badly protected if treated by the volunteers themselves. The back was better protected if another person had applied the sunscreen. In the laboratory, the fluorescent dye-containing sunscreen showed the same pattern of sunscreen application as at the beach. CONCLUSIONS: In real life, at the beach, very little sunscreen remains present on the skin.
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The knowledge of penetration pathways in and through the skin is a prerequisite for the development and optimization of topically applied drugs and cosmetics. Skin penetration has been assumed to occur via diffusion though the lipid domains of the stratum corneum. Recent studies show that the skin appendages, especially the hair follicles, play an important role in skin penetration processes. Topically applied substances cannot enter all follicles. We discuss the reasons for the phenomenon of open and closed hair follicles.
Derivatives of dimethylalkylchlorosilanes are novel substances which may be used in formulations for drug targeting. In order to design their properties it is essential to perform physicochemical characterization. For this purpose, a combination of differential scanning calorimetry (DSC), FT-Raman spectroscopy and X-ray diffraction is well suited. For the starting material dimethyloctadecylchlorosilane (DMOC), the assignment of Raman bands is discussed. The influence of sugar-containing head groups on the structures of the hydrocarbon chains of 1-O-(dimethyldodecylsilyl)-[2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside] and 1-O-(dimethyloctadecylsilyl)-[2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside] was investigated using the band position of the symmetric methylene mode. The temperature dependence of conformationally sensitive bands in the CH(2)-stretching region (2800-2900 cm(-1)), C-C-stretching region (1000-1150 cm(-1)) and CH(3)-rocking region (830-900 cm(-1)) was studied to characterize the state of order of the alkyl chains. Using X-ray diffraction, the repeating distances of layered structures was determined. The phase transitions occurring were found to be completely reversible. The subcell of DMOC shows an orthorhombic perpendicular packing structure in the crystalline state.
For 1 week, healthy human participants ( n=7) were devoid of normal vision by exposure to prism lenses that optically rotated their perceived world around the line of sight by 180 degrees. Adaptation to such prisms involved sustained and vigorous practice of the ability to redirect the unadapted efferent motor command; because prior to all visually guided movements, the to-be-executed efferent command was based on incorrect (prismatically reversed) spatial information. The time course of this sort of adaptation was systematically explored in Cooper-Shepard mental rotation (MR) tests and in naturalistic motor-tasks for the purpose of investigating whether mental rotations of the direction of the intended movement share common aspects with the process of MR. A control group ( n=7) intermittently exposed to the distorted spatial organization of the central visual field was studied in parallel. The main results were as follows: (a) the MR reaction times (RTs) day 1 with prisms appeared to be very similar to the normal RTs (day 1, no-prisms) with the one exception that subjects now responded within a prism (rotated) frame of spatial reference rather than within the environmentally upright. The visuomotor performance became grossly irregular and dysmetric. (b) The majority of the visuomotor adaptation functions began to level off on the 3rd day. (c) The increases in natural motor proficiency were accompanied by a systematic and noticeable decrease in magnitude of the MR Y-intercept obtained from the linear regression line calculated between each subject's RT and the various stimulus angles. MR slopes were stable through days 1-7 for both the experimental and control group. An increased correlation between rotational stimulus angle and RT suggested that the MR function also became progressively more tightly coupled to the stimulus angles. (d) Postadaptation measures of performance indicated the occurrence of selective and minimal adaptation in the natural motor tasks only. It is suggested that these results reflect an improved attentional (strategic) ability to replace incorrect (error producing) control signals with correct (error reducing) control signals. As a result, perceptual-motor start-up processes directly related to spatial coding and to the planning, initiation and correction of the intended direction of motor-or-mental movement improved while the subprocess ("stage") concerned with transformations of such movements remained unchanged. Visuomotor adaptation to inverting prisms engages, and thereby stimulates, a cortical system also invoked in the preparatory process of MR.
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Effects of the lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid were studied in cultured murine microglia using the patch-clamp and video imaging techniques. Both lysophospholipids induced transient membrane hyperpolarization and K(+) current activation. The lysophospholipid-induced K(+) current was blocked by charybdotoxin or iberiotoxin, but was unaffected by apamin. In recordings with 1 microM intracellular free Ca(2+), Ca(2+)-dependent K(+) currents of microglia showed a similar pharmacological profile to lysophospholipid-induced currents. The Ca(2+)-dependent K(+) channels activated in microglia by lysophospholipids are most likely encoded by the IKCa1 channel gene. The presence of IKCa1 mRNA in microglia was demonstrated by reverse transcriptase-polymerase chain reaction studies. Ca(2+) imaging experiments revealed increases in the intracellular free Ca(2+) concentration of microglia to a mean value of about 400 nM after application of 1 microM sphingosine-1-phosphate or 1 microM lysophosphatidic acid. We suggest that the transient membrane hyperpolarization seen in microglia following exposure to sphingosine-1-phosphate or lysophosphatidic acid is caused by activation of IKCa1 Ca(2+)-dependent K(+) channels. Increases in the concentration of intracellular free Ca(2+) evoked by the lysophospholipids are sufficient to activate microglial Ca(2+)-dependent K(+) channels.
A study is presented on laboratory-scale combustion of polystyrene (PS) to identify staged-combustion conditions that minimize emissions. Batch combustion of shredded PS was conducted in fixed beds placed in a bench-scale electrically heated horizontal muffle furnace. In most cases, combustion of the samples occurred by forming gaseous diffusion flames in atmospheric pressure air. The combustion effluent was mixed with additional air, and it was channeled to a second muffle furnace (afterburner) placed in series. Further reactions took place in the secondary furnace at a residence time of 0.7 s. The gas temperature of the primary furnace was varied in the range of 500-1,000 degrees C, while that of the secondary furnace was kept fixed at 1,000 degrees C. Sampling for CO, CO2, O2, soot, and unburned hydrocarbon emissions (volatile and semivolatile, by GC-MS) was performed at the exits of the two furnaces. Results showed that the temperature of the primary furnace, where PS gasifies, is of paramount importance to the formation and subsequent emissions of organic species and soot. Atthe lowesttemperatures explored, mostly styrene oligomers were identified at the outlet of the primary furnace, but they did not survive the treatment in the secondary furnace. The formation and emission of polycyclic aromatic hydrocarbons (PAH) and soot were suppressed. As the temperature in the first furnace was raised, increasing amounts of a wide range of both unsubstituted and substituted PAH containing up to at least seven condensed aromatic rings were detected. A similar trend was observed for total particulate yields. The secondary furnace treatment reduced the yields of total PAH, but it had an ambiguous effect on individual species. While most low molecular mass PAH were reduced in the secondary furnace, concentrations of some larger PAH increased under certain conditions. Thus, care in the selection of operating conditions of both the primary furnace (gasifier/ burner) and the secondary furnace (afterburner) must be exercised to minimize the emission of hazardous pollutants. The emissions of soot were also reduced in the afterburner but not drastically. This indicates that soot is indeed resistant to oxidation; thus, it would be best to avoid its formation in the first place. An oxidative pyrolysis temperature of PS in the vicinity of 600 degrees C appears to accomplish exactly that. An additional afterburner treatment at a sufficiently high temperature (1,000 degrees C) may be a suitable setting for minimization of most pollutants. To obtain deeper understanding of chemical processes, the experimental results were qualitatively compared with preliminary predictions of a detailed kinetic model that describes formation and destruction pathways of chemical species including most PAH observed in the present work. The modeling was performed forthe secondary furnace assuming plug-flow conditions therein. The experimentally determined chemical composition at the outlet of the primary furnace was part of the input parameters of the model calculation.
BACKGROUND: Several methods have been developed to improve the efficacy of mechanical resuscitation, because organ perfusion achieved with conventional manual resuscitation is often insufficient. In animal studies, phased chest and abdominal compression-decompression resuscitation by use of the Lifestick device has resulted in a better outcome compared with that of conventional resuscitation. In end-of-life patients, an increased coronary perfusion pressure was achieved. The aim of the present study was to determine the feasibility, safety, and efficacy of the Lifestick compared with conventional resuscitation in patients with sudden nontraumatic out-of-hospital cardiac arrest. METHODS AND RESULTS: The crews of 4 mobile intensive care units, staffed by an emergency physician and a paramedic, were trained to use the device. Fifty patients were randomized by sealed envelopes to either Lifestick (n=24) or conventional (n=26) resuscitation. No differences were found regarding demographic and logistical conditions between the groups. Nineteen of the patients (73%) with conventional resuscitation had ventricular fibrillation, 13 of whom survived to hospital admission (no survivals with other arrhythmias) and 7 were discharged. In contrast, in the Lifestick-CPR group, only 9 patients had ventricular fibrillation (38%; P=<0.02; OR, 2.5; 95% CI, 0.6 to 10.6). Four of these 9 patients and 5 of 15 patients with other arrhythmias survived to hospital admission, but none survived to hospital discharge. Autopsy in a subgroup of patients who died at the scene revealed less injuries with Lifestick than with conventional resuscitation. CONCLUSION: Lifestick resuscitation is feasible and safe and may be advantageous in patients with asystole or pulseless electric activity.
The heterofermentative lactic acid bacterium Oenococcus oeni requires pantothenic acid for growth. In the presence of sufficient pantothenic acid, glucose was converted by heterolactic fermentation stoichiometrically to lactate, ethanol and CO2. Under pantothenic acid limitation, substantial amounts of erythritol, acetate and glycerol were produced by growing and resting bacteria. Production of erythritol and glycerol was required to compensate for the decreasing ethanol production and to enable the synthesis of acetate. In ribose fermentation, there were no shifts in the fermentation pattern in response to pantothenate supply. In the presence of pantothenate, growing O. oeni contained at least 10.2 microM HSCoA, whereas the HSCoA content was tenfold lower after growth in pantothenate-depleted media. HSCoA and acetyl-CoA are cosubstrates of phosphotransacetylase and acetaldehyde dehydrogenase from the ethanol pathway. Both enzymes were found with activities commensurate with their function in ethanol production during heterolactic fermentation. From the kinetic data of the enzymes and the HSCoA and acetyl-CoA contents, it can be calculated that, under pantothenate limitation, phosphotransacetylase, and in particular acetaldehyde dehydrogenase activities become limiting due to low levels of the cosubstrates. Thus HSCoA deficiency represents the major limiting factor in heterolactic fermentation of glucose under pantothenate deficiency and the reason for the shift to erythritol, acetate, and glycerol fermentation.
BACKGROUND: Accelerated coronary artery disease (ACAD), a serious consequence after heart transplantation, is characterized by diffuse, concentric myointimal proliferation in the arteries. Increasing evidence supports the existence of a local renin-angiotensin system and the role of angiotensin-II in smooth muscle cell proliferation. We investigated the effect of angiotensin-II blocker candesartan and angiotensin-converting enzyme (ACE) inhibitor enalapril on experimental ACAD in a rat model. METHODS: After heterotopic cardiac transplantation (Fisher to Lewis), recipients received 20 mg/kg/day candesartan or 40 mg/kg/day enalapril per os. Two groups of animals received additional pre-treatment with candesartan or enalapril 7 days before transplantation, and treatment was continued after grafting. All study groups including the controls received 3 mg/kg/day of sub-cutaneous cyclosporine for immunosuppression. A syngeneic group (Lewis to Lewis), serving as extra control, did not receive any treatment. Eighty days after grafting, we assessed the extent of ACAD in large and small arteries, using digitizing morphometry and expressed as mean vascular occlusion (MVO). RESULTS: In enalapril and candesartan pre- and post-treated animals, we observed significant reduction of MVO of intramyocardial arteries compared with the cyclosporine group (p < 0.005), to levels similar to the syngeneic transplants. MVO of epicardial arteries in enalapril and candesartan pre- or posttreated animals did not significantly differ from cyclosporine controls (p > 0.05). CONCLUSION: Our results support the hypothesis of 2 proliferative compartments in the development of ACAD, with differing receptor or enzyme distribution: the compartment of small, intramyocardial arteries in which ACAD can be reduced by ACE or AT(1) blockade, and that of large, epicardial arteries in which inhibition fails.
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Previous investigations have shown that NO-producing nitric oxide synthase (NOS)-1 and CO-generating heme oxygenase (HO-2) are associated with the sarcolemma of skeletal muscle fibers in many mammalian species. Despite numerous roles ascribed to NO and possibly also CO in skeletal muscle, a specific receptor for both gases has hitherto not been found in myofibers. Therefore, in the present work the appearance of the alpha1, beta1 and beta2 subunits of soluble guanylate cyclase (sGC), the most commonly known receptor for NO and potentially also CO, was analysed in mammalian skeletal muscles using immunoblotting and immunohistochemistry. Immunoblotting with an antibody against the beta1 subunit of sGC revealed a band of 70 kDa corresponding to the molecular weight of this protein. Immunohistochemistry with antibodies against the alpha1, beta1 and beta2 sGC subunits showed that the larger part of positivity was present in the sarcolemma region of skeletal muscle fibers and colocalized with NOS-1 mainly in type II myofibers and with HO-2 in type I and type II myofibers. For the first time, sarcolemmal association of sGC and its colocalization with NOS-1 generating the sGC-activator NO and with HO-2 producing the potential sGC upregulator CO have been demonstrated in the present study. These results enable a better understanding of the role of NO and CO in myofibers and suggest a so far unknown molecular mechanism for the interaction of sGC with the sarcolemma.
BACKGROUND: The role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear. AIM: To investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma. METHODS: A total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 microg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period. RESULTS: Thirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD. CONCLUSION: Improvement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.
The influence of specific follicle properties, sebum production and hair growth on the follicular penetration of topically applied substances was investigated. The behavior of follicles identified in selected skin areas of volunteers was analyzed by various tape stripping and staining methods in combination with laser scanning microscopy. Furthermore hair growth in the selected skin areas was determined. A correlation between sebum production, hair growth activity and follicular penetration was observed.
PURPOSE: In this paper initial clinical observations with the application of a new low-field MR system in acute musculoskeletal imaging in radiology are presented. MATERIALS AND METHODS: This system is designed as a three-sided open permanent magnet with a revolving table. Main magnetic field strength is 0.2 T, maximal gradient field strength 20 mT/m, and minimal gradient rise time is 800 microseconds. First clinical experiences in 25 patients with acute trauma of peripheral joints were obtained. The following sequences were applied: gradient-echo (GRE) STIR, T1-weighted spin-echo, and PD- and T2-weighted turbo spin-echo. Correlation with the findings of high-field MR (1.5 T), plain radiograms (including stress views), CT or ultrasound was available in each patient confirming the low-field diagnoses. Furthermore, phantom measurements were performed to verify the spatial resolution of the system for some sequences with typical measurement parameters. DISCUSSION: This low-field system has several advantages: fast and economic installation, limited required space, easy operation, and high patient comfort. The medical benefit of such a system integrated in the traumatological suite of a radiological department seems to be evident due to the impact on the early initiation of the correct therapy which avoids additional diagnostic procedures and therefore may reduce costs. Implementation of such a system may be useful, if installation of an additional high-field scanner is not possible due to economic considerations.