Günther A, Salzmann I, Nowack S, Schwab M, Surber R, Hoyer H, Witte OW, Hoyer D. Heart rate variability - a potential early marker of sub-acute post-stroke infections. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2011.01626.x. © 2011 John Wiley & Sons A/S. Objective -  Infection is the most relevant complication after acute ischemic stroke. Activity of the autonomic nervous system seems to control post-stroke immunodepression. We investigated heart rate variability (HRV) indices that reflect autonomic readjustments as predictors of post-stroke infection. Materials and methods -  Forty-three patients with acute ischemic stroke were enrolled in a prospective study. The predictability of sub-acute infections (day 4 ± 1 after admission) was investigated in 34 patients without acute infection by means of HRV indices obtained in the acute period (48 h after admission). Results -  Sub-acute infection could be predicted in patients without clinical or paraclinical (white blood cell count and C-reactive protein) signs of infection in the acute period at (i) day: increased HFnorm, reduced LFnorm and LF/HF;(ii) night: reduced LF and VLF (P < 0.05). Conclusions -  HRV indices are candidates for early markers of developing post-stroke infections, preceding routine blood samples. Thus, HRV-based early diagnosis of post-stroke infection should be investigated in more detail as it may have implications as a novel tool for timely and appropriate treatment. A corresponding continuous HRV-based risk assessment using the ECG provided by the routine stroke monitoring system would be possible without any additional burden for patients and staff.

Bärthel E, Rauchfuß F, Hoyer H, Habrecht O, Jandt K, Götz M, Voigt R, Heise M, Marx G, Settmacher U. Impact of stable PGI(2) analog iloprost on early graft viability after liver transplantation: a pilot study. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01516.x. © 2011 John Wiley & Sons A/S. Abstract:  Background:  Ischemia/reperfusion injury after liver transplantation (LT) may be associated with primary graft dysfunction (PDF) or non-function. Prostaglandins were demonstrated to be beneficial in reducing ischemic injury by improving microcirculation and protecting endothelial cells. The aim of this study was to analyze the effect of the continuously administered prostaglandin I(2) analog iloprost on allograft function after LT. Methods:  Eighty patients were prospectively randomized and assigned to two groups. Patients in the treatment group received iloprost for seven d after transplantation, and those in the control group did not. The primary end point was graft dysfunction. Results:  The incidence of PDF was 20%(n = 8) in the control group and 5%(n = 2) in the treatment group, respectively (p = 0.087). Four patients in the control group underwent re-transplantation for initial non-function (INF). There was no evidence for INF in the treatment group. Iloprost was associated with improved allograft function. Clinical course and outcome were comparable. Conclusions:  We suggest iloprost to be beneficial for early post-transplant liver function. If the rate of PDF can be significantly reduced with this treatment concept, it should be analyzed in a larger number of patients (ISRCTN95672167).

The purpose of this study was to develop and evaluate an oral oligonucleotide delivery system based on a thiolated polymer/reduced glutathione (GSH) system providing a protective effect toward nucleases and permeation enhancement. A polycarbophil-cysteine conjugate (PCP-Cys) was synthesized. Enzymatic degradation of a model oligonucleotide by DNase I and within freshly collected intestinal fluid was investigated in the absence and presence of PCP-Cys. Permeation studies with PCP-Cys/GSH versus control were performed in vitro on Caco-2 cell monolayers and ex vivo on rat intestinal mucosa. PCP-Cys displayed 223 ± 13.8 μmol thiol groups per gram polymer. After 4h, 61% of the free oligonucleotides were degraded by DNase I and 80% within intestinal fluid. In contrast, less than 41%(DNase I) and 60%(intestinal fluid) were degraded in the presence of 0.02%(m/v) PCP-Cys. Permeation studies revealed an 8-fold (Caco-2) and 10-fold (intestinal mucosa) increase in apparent permeability compared to buffer control. Hence, this PCP-Cys/GSH system might be a promising tool for the oral administration of oligonucleotides as it allows a significant protection toward degrading enzymes and facilitates their transport across intestinal membranes.

The Eurasian lineages of swine influenza viruses are different genetically from classical swine H1N1 influenza viruses and comprise avian-like H1N1 and human-like H1N2 and H3N2 subtypes. Although sporadic isolation of such viruses from human specimens has been reported, the prevalence of human infections is not known. In the present study, the seroprevalence against Eurasian swine influenza viruses was investigated. Sera were collected in Thuringia, Germany, from December 2007 to April 2009. The study group comprised 118 professionals with occupational exposure to pigs (50 pig slaughterers/meat inspectors, 46 pig farmers, 22 veterinarians caring for pig herds). The control group included 118 age- and gender-matched blood donors from Thuringia. As a result, 18 sera of the study group were identified with raised hemagglutination-inhibition titers against a panel of nine swine influenza viruses (three strains/ subtype). For 17/18 sera this finding was confirmed in the neutralization assay. For 11/18 sera the raise of titers was significant, that is, a fourfold increase of hemagglutination-inhibition titers was observed. No gender-specific bias of the high titer sera was observed. Twelve sera of the control group showed increased hemagglutination-inhibition titers against swine influenza viruses. Hemagglutination-inhibition titers of 2/12 control sera were raised fourfold but did not exhibit a significant increase of neutralization titers. All increased hemagglutination-inhibition titers of the control group may be explained by cross-reactivity with seasonal influenza virus strains, as all these sera also reacted with human strains.

Epidemiological, clinical and radiological data of 1266 patients with a unilateral acetabular fracture of up to 29 hospitals was reviewed. Three time periods, 1991-1993 (Registry I; n=359), 1998-2000 (Registry II; n=503), and 2005-2006 (Registry III; n=404) were compared with regard to injury pattern and severity, fracture type, and chosen nonoperative vs. operative treatment to elucidate changes over time in the treatment of acetabular fractures. In the operatively treated group, time to operation, surgical approach, fracture fixation implants and fracture reduction quality were examined. 641 (50.6%) patients with isolated acetabular fractures, 410 (32.4%) multiple injured and 215 (17.0%) polytrauma patients with 642 (50.7%) simple and 624 (49.3%) associated acetabular fractures were evaluated. In the time period from 1991 to 2006, the rate of operative treatments increased nationwide to 77%(rho<0.001). The distribution of fracture types involving the anterior and posterior wall changed with age (rho<0.001). Across all registries, 583 (68.0%) operations were performed within 7 days, 212 (24.7%) operations between 7 and 14 days and 54 (6.3%) operations were performed later than 14 days after injury. An anatomical reduction (0-1mm displacement) was achieved in 551 (64%) acetabular fractures. The obtained reduction quality did not correlate with time to operation, was lower in associated than in simple fracture types, and also lower in patients with isolated acetabular fractures than in polytrauma patients. Most importantly, the fracture reduction quality did not improve over time despite a higher frequency of surgical interventions. The Kocher-Langenbeck approach was preferred in the nineties in nearly three quarters of all operative procedures. Currently, the Kocher-Langenbeck and the ilioinguinal approaches are used equally often. The fracture fixation did not change over time and is achieved in 51% with plates in combination with single screws. This multisurgeon series illustrates a nationwide performance in acetabular fracture management. Despite changes in the chosen approaches and an increased surgical frequency, the operative treatment of acetabular fractures of the last 15 years did not lead to an increased reduction quality. Therefore, the rarity and complexity of acetabular fractures demands further specific teaching by experienced acetabular surgeons, scientific research and clinical outcome evaluation.

The aim of this study was to establish and evaluate a high pressure homogenization method for the preparation of thiomer nanoparticles. Particles were formulated by incorporation of the model protein horseradish peroxidase in chitosan-glutathione (Ch-GSH) and poly(acrylic acid)-glutathione (PAA-GSH) via co-precipitation followed by air jet milling. The resulting microparticles were suspended in distilled water using an Ultraturax and subsequently micronized by high pressure homogenization. Finally, resulting particles were evaluated regarding size distribution, shape, zeta potential, drug load, protein activity and release behaviour. The mean particle size after 30 cycles with a pressure of 1500 bar was 538 +/- 94 nm for particles consisting of Ch-GSH and 638 +/- 94 nm for particles consisting of PAA-GSH. Nanoparticles of Ch-GSH had a positive zeta-potential of +1.03 mv, whereas nanoparticles from PAA-GSH had a negative zeta potential of -6.21 mv. The maximum protein load for nanoparticles based on Ch-GSH and based on PAA-GSH was 45 +/- 2% and 37 +/-%, respectively. The release profile of nanoparticles followed a first order release kinetic. Thiolated nanoparticles prepared by a high pressure homogenization technique were shown to be stable and provide controlled drug release characteristics. The preparation method described here might be a useful tool for a more upscaled production of nanoparticulate drug delivery systems.

ABSTRACT: BACKGROUND: Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. METHODS: Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included. We screened for point mutations in the MFN2 gene. RESULTS: We identified four known and three novel point mutations in 8 unrelated CMT families. The novel point mutations were not found in 100 healthy controls. This corresponds to 3.4%(8/232) of CMT families have point mutations in the MFN2 gene. The phenotypes were compatible with CMT1 in two families, CMT2 in four families, intermediate CMT in one family and distal Hereditary Motor Neuropathy (dHMN) in one family. This corresponds to 2.3% of CMT1, 5.5% of CMT2, 12.5% of intermediate CMT and 6.7% of dHMN families have a point mutation in the MFN2 gene. Point mutations in the MFN2 gene is likely to be the fourth most common cause to CMT after duplication of the peripheral myelin protein 22 (PMP22) gene, and point mutations in the Connexin32 (Cx32) and myelin protein zero (MPZ) genes. CONCLUSIONS: The identified known and novel point mutations in the MFN2 gene expand the clinical spectrum from CMT2 and intermediate CMT to also include possibly CMT1 and the dHMN phenotypes. Thus, genetic analyses of the MFN2 gene should not be restricted to persons with CMT2.

BACKGROUND: Sonography is an established diagnostic procedure in hospitals, but is not routinely used in prehospital emergency medicine. Several studies have addressed the use of ultrasound during helicopter flights and in emergency rooms, few in prehospital settings, but most focused on abdominal blunt trauma. Several case reports describe crucial decisions distinguished by ultrasound. METHODS: In this study, four different handheld ultrasound systems in 4 helicopters and one emergency vehicle were used over a cumulative period of 3 years. Incidence, feasibility, indication, diagnoses and exploration time (in subgroups) were investigated in an overall profile of emergency patients, encompassing the area of internal medicine. RESULTS: On 971 missions ultrasound systems were available. In 17% of the cases ultrasound was considered valuable, in 144 patients (14.8%) sonographic studies were performed. Additional information could be given in 130 cases (90%). Compared with the available clinical data (return rate of 76%) there were no false-positive findings during this study, resulting in a specificity and positive predictive value of 100%, showing this technique to be reliable. Sensitivity was 85%, accuracy was 96% and negative predictive value was 95%. CONCLUSION: Ultrasound is the only imaging modality and a useful diagnostic tool in prehospital emergency medicine. Helpful information can be provided in at least one of six cases (or even more) in a trauma-dominated collective. Examination time is short; it will not significantly delay medical care. Ultrasound examination could improve triage in cases of more than one patient in disaster medicine, but further studies are necessary.

BACKGROUND: Influenza is associated with substantial morbidity and mortality in pregnant women and neonates, but few countries offer annual influenza vaccination with the inactivated vaccine to all women who are, or intend to become, pregnant. OBJECTIVES: To provide seroepidemiological information on influenza A and B antibodies in pregnant women and their offspring in Germany. STUDY DESIGN: Anti-influenza antibodies were determined using commercially available enzyme-linked immunosorbent assays (ELISA) on serum obtained from 209 women and their newborns at delivery. RESULTS: The prevalence of antibodies against influenza A virus was 93.8%[89.6-96.6%] in the mothers and 96.7%[93.2-98.6%] in the newborns. The prevalence of antibodies against influenza B virus was 42.1%[35.3-49.1%] in the mothers and 78.5%[72.3-83.8%] in their newborns, which was a significant difference. The antibody concentrations against both influenza A and influenza B viruses were significantly lower in mother than in their newborns. CONCLUSIONS: Because of active placental transport of IgG antibodies, neonates have higher prevalence and/or concentrations of influenza A and B virus-specific antibodies induced by natural infections than their mothers. Considering these serological findings, especially the lower prevalence of maternal antibody against influenza B virus, annual influenza vaccination may improve the protection of pregnant women and their offspring against influenza.

Objective: The aim of this review is to provide the reader general and inspiring prospects in various attempts to make noninvasive delivery systems of calcitonin and teriparatide feasible and as convenient as possible. Background: Calcitonin and teriparatide play an important role in both calcium homeostasis and bone remodelling. Currently calcitonin is available as a subcutaneous injection and as a nasal spray whereas teriparatide is administered subcutaneously. In the past few years, an increasing number of articles about drug delivery systems for calcitonin and teriparatide have been published. These delivery systems have been developed to overcome the inherent barriers for the uptake across the diverse membranes on the various routes for protein and peptide delivery. Results: Co-administration of permeation enhancers, mucoadhesive agents, viscosity modifying agents, multifunctional polymers, protease inhibitors as well as encapsulation and chemical modification are utilized in order to improve calcitonin and teriparatide absorption after oral, nasal, pulmonal, or buccal administration. Conclusion: The majority of research groups have been working on the development of formulations based on the encapsulation of molecules in biodegradable and biocompatible polymeric nanoparticles. However these observations are based on data obtained under different experimental conditions. Hence, it is difficult to compare the obtained results in order to draw general conclusions about the most promising characteristics required for oral and nasal formulations for these peptides.