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1.  Rapid optical control of nociception with an ion channel photoswitch 
Nature methods  2012;9(4):396-402.
Local anesthetics are effective in suppressing pain sensation, but most of these compounds act non-selectively, inhibiting the activity of all neurons. Moreover, their actions abate slowly, preventing precise spatial and temporal control of nociception. We have developed a photoisomerizable molecule named QAQ (Quaternary ammonium – Azobenzene – Quaternary ammonium) that enables rapid and selective optical control of nociception. QAQ is membrane-impermeant and it has no effect on most cells, but it infiltrates pain-sensing neurons through endogenous ion channels that are activated by noxious stimuli, primarily TRPV1. After QAQ accumulates intracellularly, it blocks voltage-gated ion channels in the trans but not the cis form. QAQ enables reversible optical silencing of mouse nociceptive neuron firing without exogenous gene expression and can serve as a light-sensitive analgesic in rats in vivo. Moreover, because intracellular QAQ accumulation is a consequence of nociceptive ion channel activity, QAQ-mediated photosensitization provides a new platform for understanding signaling mechanisms in acute and chronic pain.
doi:10.1038/nmeth.1897
PMCID: PMC3906498  PMID: 22343342
2.  Anticoagulative strategies in reconstructive surgery – clinical significance and applicability 
GMS German Medical Science  2012;10:Doc01.
Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated.
However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized.
Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances.
The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications.
doi:10.3205/000152
PMCID: PMC3263521  PMID: 22294976
anticoagulation; microsurgery; heparin-induced thrombocytopenia (HiT); thrombosis
3.  Acute effects of remote ischemic preconditioning on cutaneous microcirculation - a controlled prospective cohort study 
BMC Surgery  2011;11:32.
Background
Therapeutic strategies aiming to reduce ischemia/reperfusion injury by conditioning tissue tolerance against ischemia appear attractive not only from a scientific perspective, but also in clinics. Although previous studies indicate that remote ischemic intermittent preconditioning (RIPC) is a systemic phenomenon, only a few studies have focused on the elucidation of its mechanisms of action especially in the clinical setting. Therefore, the aim of this study is to evaluate the acute microcirculatory effects of remote ischemic preconditioning on a distinct cutaneous location at the lower extremity which is typically used as a harvesting site for free flap reconstructive surgery in a human in-vivo setting.
Methods
Microcirculatory data of 27 healthy subjects (25 males, age 24 ± 4 years, BMI 23.3) were evaluated continuously at the anterolateral aspect of the left thigh during RIPC using combined Laser-Doppler and photospectrometry (Oxygen-to-see, Lea Medizintechnik, Germany). After baseline microcirculatory measurement, remote ischemia was induced using a tourniquet on the contralateral upper arm for three cycles of 5 min.
Results
After RIPC, tissue oxygen saturation and capillary blood flow increased up to 29% and 35% during the third reperfusion phase versus baseline measurement, respectively (both p = 0.001). Postcapillary venous filling pressure decreased statistically significant by 16% during second reperfusion phase (p = 0.028).
Conclusion
Remote intermittent ischemic preconditioning affects cutaneous tissue oxygen saturation, arterial capillary blood flow and postcapillary venous filling pressure at a remote cutaneous location of the lower extremity. To what extent remote preconditioning might ameliorate reperfusion injury in soft tissue trauma or free flap transplantation further clinical trials have to evaluate.
Trial registration
ClinicalTrials.gov: NCT01235286
doi:10.1186/1471-2482-11-32
PMCID: PMC3231986  PMID: 22111972
Remote ischemic preconditioning; cutaneous microcirculation; free flap; soft tissue
4.  MRI-Based Breast Volumetry—Evaluation of Three Different Software Solutions 
Journal of Digital Imaging  2010;23(5):603-610.
As lipofilling of the female breast is becoming more popular in plastic surgery, the use of MRI to assess breast volume has been employed to control postoperative results. Therefore, we sought to evaluate the accuracy of magnetic resonance imaging (MRI)-based breast volumetry software tools by comparing the measurements of silicone implant augmented breasts with the actual implant volume specified by the manufacturer. MRI-based volume analysis was performed in eight bilaterally augmented patients (46 ± 9 years) with three different software programs (Brainlab© I plan 2.6 neuronavigation software; mass analysis, version 5.3, Medis©; and OsiriX© v.3.0.2. 32-bit). The implant volumes analysed by the BrainLab© software had a mean deviation of 2.2 ± 1.7% (r = 0.99) relative to the implanted prosthesis. OsiriX© software analysis resulted in a mean deviation of 2.8 ± 3.0% (r = 0.99) and the Medis© software had a mean deviation of 3.1 ± 3.0% (r = 0.99). Overall, the volumes of all analysed breast implants correlated very well with the real implant volumes. Processing time was 10 min per breast with each system and 30 s (OsiriX©) to 5 min (BrainLab© and Medis©) per silicone implant. MRI-based volumetry is a powerful tool to calculate both native breast and silicone implant volume in situ. All software solutions performed well and the measurements were close to the actual implant sizes. The use of MRI breast volumetry may be helpful in: (1) planning reconstructive and aesthetic surgery of asymmetric breasts, (2) calculating implant size in patients with missing documentation of a previously implanted device and (3) assessing post-operative results objectively.
doi:10.1007/s10278-009-9264-y
PMCID: PMC3046681  PMID: 20066465
MRI; volumetry; mamma; breast; lipofilling; silicone implant; BrainLab; OsiriX; Medis
5.  Clivus Chordoma in Continuity with a Large Pontine Cyst 
Skull Base  2009;19(2):177-181.
ABSTRACT
Chordomas are tumors commonly of extradural origin associated with bone destruction; their central nervous system invasion has rarely been reported. The authors describe a rare case of a 37-year-old man presenting with a clivial chordoma invading the brainstem with a large pontine cyst. A median suboccipital approach was selected to remove the tumor.
doi:10.1055/s-0028-1096208
PMCID: PMC2671305  PMID: 19721775
Chordoma; skull base; cyst; clivus
6.  Evaluation of Marrow Perfusion in the Femoral Head by Dynamic Magnetic Resonance Imaging 
Investigative radiology  1992;27(4):275-281.
Rationale and Objectives
There is a continuing need for a greater sensitivity of magnetic resonance imaging (MRI) in the diagnosis of avascular necrosis (AVN). Previously, it was demonstrated that a dynamic MRI method, with gadolinium-DTPA (Gd-DTPA) enhancement, can detect acute changes not seen on spin-echo images after arterial occlusion in a dog model. Because venous congestion appears to be a more directly relevant hemodynamic abnormality in a majority of clinical AVN cases, the authors extended the dynamic MRI technique to study changes in venous occlusion.
Methods
Dynamic MRI of the proximal femur was performed in five adult dogs before and after unilateral ligation of common iliac and lateral circumflex veins. Sixteen sequential gradient-recalled pulse sequence (GRASS) images (time resolution = 45 mseconds, echo time = 9 mseconds, flip angle = 65°) were obtained immediately after a bolus intravenous injection of 0.2 mmol/kg of Gd-DTPA. Simultaneous measurements of regional blood flow were made using the radioactive microsphere method.
Results
After venous ligation, there was a 25% to 45% decrease in the degree of enhancement compared with preligation values on the ligated side. The decrease in cumulative enhancement (integrated over the entire time course) was statistically significant. The occlusion technique was verified by confirming a statistically significant decrease in blood flow determined by the microsphere method.
Conclusions
Dynamic Gd-DTPA-enhanced fast MRI technique can detect acute changes in bone marrow perfusion due to venous occlusion. This technique may have applications in the early detection of nontraumatic AVN.
PMCID: PMC2396275  PMID: 1601616
avascular necrosis; dynamic magnetic resonance imaging; femur; gadolinium-DTPA; magnetic resonance imaging; venous occlusion

Results 1-6 (6)