The importance of the biology and the care for the soft tissues and bone during internal fixation of the fracture, as the fourth AO principle, had been stressed. A conventional AO compression plate pressed against the bone surface interferes with the cortical blood flow and induces structural changes underneath the plate. Low contact dynamic contact plate(LC- DCP) could reduce the area of contact between plate and bone undercuts. Locking head screws, the Point Contact Fixator (PC Fix), and the Less Invasive Stabilisation System (LISS) had the next evolution.The so- called internal fixator can be considered as an external fixator, which has been approximated very close to the bone, however, without actually touching or compressing bone. This feature prevents any additional damage to bone vascularity. The stability of the internal fixator depends on the angular stability of the screw- plate combination. The new LISS and Locking Compression Plate( LCP) offer new options and challenges in modern operative fracture care. These implants are ideal for the MIPO (minimally invasive (percutaneous) plate osteosynthesis) and appear to have a considerably better purchase in osteoporotic bone. Nevertheless, it must be stated that these new plates and screws do not solve all problems, either as they too demand a very careful planning of every procedure, which includes a re- thinking of the classical AO principles, especially when addressing meta- and diaphyseal fractures.

OBJECTIVETo investigate the molecular mechanism of human ether-a-go-go-related gene (HERG) potassium channels regulated by protein kinase A (PKA) in a human cell line.

METHODSHERG channels were stably expressed in human embryonic kidney (HEK) 293 cells, and currents were measured with the patch clamp technique. The direct phosphorylation of HERG channel proteins expressed heterologously in Xenopus laevis oocytes was examined by (32)P labeling and immunoprecipitation with an anti-HERG antibody.

RESULTSElevation of the intracellular cAMP-concentration by incubation with the adenylate cyclase activator, forskolin (10 micromol/L), and the broad range phosphodiesterase inhibitor, IBMX (100 micromol/L), caused a HERG tail current reduction of 83.2%. In addition, direct application of the membrane permeable cAMP analog, 8-Br-cAMP (500 micromol/L), reduced the tail current amplitude by 29.3%. Intracellular application of the catalytic subunit of protein kinase A (200 U/ml) led to a tail current decrease by 56.9% and shifted the activation curve by 15.4 mV towards more positive potentials. HERG WT proteins showed two phosphorylated bands, an upper band with a molecular mass of approximately 155 kDa and a lower band with a molecular mass of approximately 135 kDa, indicating that both the core- and the fully glycosylated forms of the protein were phosphorylated.

CONCLUSIONSPKA-mediated phosphorylation of HERG channels causes current reduction in a human cell line. The coupling between the repolarizing cardiac HERG potassium current and the protein kinase A system could contribute to arrhythmogenesis under pathophysiological conditions.

1-Methyl-3-isobutylxanthine ; pharmacology ; 8-Bromo Cyclic Adenosine Monophosphate ; pharmacology ; Adenylyl Cyclases ; metabolism ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Cation Transport Proteins ; Cell Line ; Colforsin ; pharmacology ; Cyclic AMP ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; DNA-Binding Proteins ; ERG1 Potassium Channel ; Enzyme Activation ; drug effects ; Ether-A-Go-Go Potassium Channels ; Female ; Humans ; Membrane Potentials ; drug effects ; Microinjections ; Oocytes ; Patch-Clamp Techniques ; Phenethylamines ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; Phosphoric Diester Hydrolases ; drug effects ; metabolism ; Phosphorylation ; Potassium Channels ; genetics ; metabolism ; physiology ; Potassium Channels, Voltage-Gated ; RNA, Complementary ; administration & dosage ; genetics ; Sulfonamides ; pharmacology ; Trans-Activators ; Transcriptional Regulator ERG ; Xenopus laevis

The originally published version of this Article contained an error in the author list: the last and first names of all authors are inverted.

OBJECTIVE: We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. MATERIALS AND METHODS: An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). RESULTS: Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. CONCLUSION: Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans.
Female ; *Four-Dimensional Computed Tomography ; Humans ; Male ; Neoplasms/*blood supply/*radiography ; Phantoms, Imaging ; *Radiation Dosage

OBJECTIVES: Though sulfur dioxide (SO2) is used widely at workplaces, itseffects on humans are not known. Thresholds are reportedwithout reference to gender or age and occupational exposure limits are basedon effects on lung functioning,although localized effects in the upper airways can be expected.This study's aim is to determine thresholds with respect to age and gender and suggests a new approach to risk assessment using breathing reflexes presumably triggered by trigeminal receptors in the upper airways. METHODS: Odor thresholds were determined by the ascending method of limits in groups stratified by age and gender.Subjects rated intensities of different olfactory and trigeminal perceptions at different concentrations of SO2. During the presentation of the concentrations, breathing movements were measured by respiratory inductive plethysmography. RESULTS: Neither age nor gender effects were observed for odor threshold. Only ratings of nasal irritation were influenced bygender. A benchmark dose analysis on relative respiratory depth revealed a 10%-deviation from baseline at about 25.27 mg/m3. CONCLUSION: The proposed new approach to risk assessment appearsto be sustainable. We discuss whether a 10%-deviation of breathingdepth is relevant.
Human Experimentation ; Humans ; Lung ; Occupational Exposure ; Odors ; Reflex ; Respiration ; Respiratory Mechanics ; Risk Assessment ; Sensory Thresholds ; Sulfur Dioxide

BACKGROUNDReportedly, patients with persistent refractory angina due to end-stage coronary artery disease (CAD) not amenable to traditional revascularization techniques have experienced symptomatic relief following laser revascularization, either surgical transmyocardial revascularization (TMR) or percutaneous myocardial revascularization (PMR). In spite of several hypotheses (i.e., channel patency, placebo effect, denervation, neoangiogenesis), the mechanism of action and the benefit remains controversial.

METHODSA prospective trial utilizing positron emission tomography (PET) was conducted as an attempt to correlate quantified myocardial blood flow (MBF) to clinical improvement following PMR. Thirteen consecutive patients with angina class > II in spite of maximal medical treatment underwent PMR with a holmium: yttrium-aluminum-garnet (Ho:YAG) laser. MBF at rest and under hyperemia was assessed by [(13)N]ammonia PET at baseline, 3 and 6 months following PMR.

RESULTSMean angina class and exercise tolerance time improved at 6 months compared with baseline (P < 0.001). The clinical results were accompanied with an improvement in hyperemic MBF (P = 0.05) and a reduction in minimal coronary resistance (MCR; P < 0.05) in PMR-treated segments. Opposite effects, reduced hyperemic MBF and increased MCR, were observed in nontreated segments. The increase in MCR in nontreated segments revealed the favorable therapeutic impact achieved in PMR-treated segments.

CONCLUSIONThe results of this trial utilizing a quantitative technique to quantify myocardial perfusion link clinical improvement post-PMR to neoangiogenesis and consistently improved microcirculation.

Aged ; Coronary Artery Disease ; diagnostic imaging ; physiopathology ; surgery ; Coronary Circulation ; Female ; Humans ; Male ; Middle Aged ; Myocardial Revascularization ; methods ; Positron-Emission Tomography ; Vascular Resistance

No abstract available.
Arteries ; Cohort Studies

PURPOSE: The aim of this study was to evaluate the technical feasibility and rate of mid-term occlusion in aneurysms treated solely with the Pipeline Embolization Device (PED) in a German tertiary care university hospital. MATERIALS AND METHODS: Forty-nine non-consecutive intracranial aneurysms underwent endovascular treatment using the PED exclusively between March 2011 and May 2017 at our institution. Primary endpoint was a favorable aneurysm occlusion defined as OKM C1-3 and D (O'Kelly Marotta Scale). Secondary endpoints were retreatment rate and delayed complications. Median follow-up was 200 days. RESULTS: The mean aneurysm size was 7.1 ± 5.3 mm. Forty-four aneurysms were located in the anterior circulation (90%). Ten aneurysms were ruptured (20%). Branching vessels from the sac were observed in 11 aneurysms (22%). Favorable obliteration immediately after PED placement was seen in 13/49 aneurysms (27%), of those nine aneurysms were completely occluded (18%). Angiographic and clinical follow-up was available for 45 cases (92%); 36/45 aneurysms (80%) were occluded completely and 40/45 aneurysms (89%) showed a favorable occlusion result. A branching vessel arising from the aneurysm sac was associated with incomplete occlusion (P < .05). All electively treated patients had good outcome (mRS 0). Three aneurysms (6%) required additional treatment due to aneurysm recurrence. CONCLUSION: In our series, treatment of intracranial aneurysms with the PED was associated with favorable occlusion rates and low complication rates at mid-term follow-up. The presence of branching vessels arising from the aneurysms sac was predictive for an incomplete occlusion.
Aneurysm ; Follow-Up Studies ; Humans ; Intracranial Aneurysm* ; Recurrence ; Retreatment ; Tertiary Healthcare

Objective:To compare the effectiveness of primary malleostapedotomy with revision malleostapedotomy for otosclerosis.Methods:From April 2002 to December 2017, 70 consecutive patients with otosclerosis who underwent malleostapedotomy were reviewed. Depending on the primary malleostapedotomy (P-MS) or revision malleostapedotomy (R-MS), the patients were divided into P-MS group or R-MS group.The intraoperative findings and hearing results before and after surgery were compared between the two groups. ALL data were analyzed using SPSS 23.Results:Totally 73 malleostapedotomy were performed in 73 ears of 70 patients, including 38 P-MS and 35 R-MS. There was no significant difference between the two groups in sex ratio, age and operated ears ( P>0.05 for all). The most common finding at P-MS was incus fixation (50.0%, 19/38) versus prosthesis displacement for R-MS (60.0%, 21/35) . Overall, the air-bone gap (ABG) improvement in P-MS were (18.1±8.2) dB in 0.5-3 kHz and (18.3±8.5) dB in 0.5-4 kHz, without significant difference to those in R-MS ( P>0.05) . 31.4% of R-MS in 0.5-3 kHz and 22.9% R-MS in 0.5-4 kHz achieved an ABG<10 dB, significantly lower than those of P-MS (65.8% in 0.5-3 kHz and 57.9% in 0.5-4kHz; P<0.05). Failure (postoperative ABG>30 dB) occurred in 11.4% in R-MS and 0 in P-MS (for 0.5-3 kHz and 0.5-4 kHz). The incidence of postoperative sensorineural hearing loss (>10 dB increase in bone conduct) in R-MS group was 8.6% in 0.5-3 kHz and 0.5-4 kHz, without significant difference to those in P-MS ( P>0.05) . 80.0% (20/25) of first R-MS achieved ABG<20 dB, compared to 37.5% (3/8) of second R-MS with ABG<20 dB. Conclusions:Although both P-MS and R-MS can significantly improve hearing, with similar risk of inner ear damage, R-MS is less effective and poses a higher risk of failure than P-MS. For patients with insufficient hearing improvement after first R-MS, conventional hearing aids or implantable hearing devices may be considered as an alternative.

Background: and Purpose Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach. Methods: A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets. Results: Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1. Conclusion Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.