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Patienten weisen im Schockzustand eine zu geringe periphere Durchblutung auf, um eine ausreichende Sauerstoffversorgung lebenswichtiger Organe, wie Herz und Gehirn, sicherzustellen. Die frühzeitige Erkennung einer verminderten Gewebesauerstoffsättigung (StO2) im Bereich der Mikrozirkulation könnte die Chance zum schnellstmöglichen Therapieeingriff bieten und auf diese Weise die Prognose von Patienten in der Frühphase eines Multiorgandysfunktionssyndroms (MODS) verbessern. Im Rahmen einer monozentrischen prospektiven randomisierten Phase-II-Studie wurde bei 60 Patienten in der Frühphase eines Multiorgandysfunktions-Syndroms (MODS) (APACHE[„Acute Physiology and Chronic Health Evaluation“]-II-Score ≥20) die StO2mittels des InSpectraTM-StO2-Systems aufgezeichnet und anschließend mit bekannten Hypoxieindikatoren (pulsoxymetrische Sauerstoffsättigung [SpO2], arterielle Sauerstoffsättigung [SaO2], zentralvenöse Sauerstoffsättigung [ScvO2], pH-Wert, Serumlaktatspiegel) verglichen. Klinische Endpunkte der Studie waren neben der 28-Tage- und 6‑Monats-Letalität auch die Notwendigkeit zur Beatmung und Nierenersatztherapie während des Klinikaufenthalts. Studienteilnehmer mit einer StO2<75 % weisen im Vergleich zu Patienten mit einer StO2≥75 % eine erhöhte 28-Tage- und 6‑Monats-Letalität auf. Hinsichtlich der Notwendigkeit zur Beatmung oder Nierenersatztherapie ergibt sich keine prognostische Aussagekraft. Des Weiteren kann eine Korrelation der StO2mit bekannten Hypoxieindikatoren, wie SpO2, ScvO2und dem Serumlaktatspiegel bestätigt werden. Ebenso zeigen Patienten mit einer reduzierten StO2tendenziell eine höhere Krankheitsschwere gemessen am APACHE-II-Score. Die StO2zeigt prognostische Relevanz bei Patienten in der Frühphase eines MODS. Die rasche und nichtinvasive Erhebung dieses Parameters könnte somit bei der Risikostratifizierung dieser Patienten von Nutzen sein. Patients in circulatory shock exhibit insufficient peripheral perfusion to ensure adequate oxygenation of vital organs such as the heart and brain. Early detection of reduced tissue oxygen saturation (StO2) could be used for rapid therapeutic intervention and thus improve the prognosis of patients in the early stage of multiple organ dysfunction syndrome (MODS). A total of 60 patients in the early stage of MODS (APACHE [Acute Physiology and Chronic Health Evaluation] II score ≥20) were investigated in a monocentric, prospective, randomized phase II study. StO2was measured using the InSpectraTM StO2system and compared with known indicators of hypoxia (peripheral oxygen saturation [SpO2], arterial oxygen saturation [SaO2], central venous oxygen saturation [ScvO2], pH, serum lactate). Clinical endpoints of the study were 28-day and 6‑month mortality as well as the need for invasive mechanical ventilation and renal replacement therapy during the hospital stay, respectively. An increased 28-day and 6‑month mortality is found for patients with StO2<75% in contrast to patients with StO2≥75%. Correlations of StO2with SpO2, ScvO2, and serum lactate are confirmed. Patients with reduced StO2tend to show a higher disease severity as measured by APACHE II score. StO2shows prognostic relevance in patients at the early stage of MODS. Thus, the rapid and noninvasive assessment of StO2could be useful in risk stratification of these patients.

Background & Aims:: In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC. Methods:: In patients with histologically confirmed cholangiocarcinoma, endoscopic or percutaneous double stenting was performed. Patients fulfilling inclusion criteria were randomized to group A (stenting and subsequent PDT) and group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm; light dose, 180 J/cm^2). Further treatments were performed in cases of residual tumor in the bile duct. The primary outcome parameter was survival time. Secondary outcome parameters were cholestasis and quality of life. Results:: PDT resulted in prolongation of survival (group A: n = 20, median 493 days; group B: n = 19, median 98 days; P < 0.0001). It also improved biliary drainage and quality of life. Conclusions:: PDT, given in addition to best supportive care, improves survival in patients with NCC. The study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.

Background: Malignant duodenal obstruction is a common event in patients with advanced biliary tract cancer. Because bypass surgery is accompanied by significant morbidity, self-expandable metallic stents have emerged as a possible alternative for palliation. Methods: Twenty patients with biliary tract cancer (7 gallbladder, 13 Klatskin tumors) and duodenal obstruction were treated with metallic stents at a single institution between 1999 and 2001. Survival, morbidity, and stent function were studied prospectively. The ability to eat was assessed by using a scoring system. Results: Stent placement was technically successful in all patients. An additional stent was required in 6 cases (4 occlusions, 2 dislocations). Median survival was 20.5 weeks; there was no treatment-related death. Twenty-eight biliary stent exchanges were performed in 13 (65%) patients. Erosive reflux esophagitis improved in 11 of 12 (92%) cases. After 4 weeks, all 17 surviving patients tolerated soft or solid food, whereas 13 of 17 (77%) tolerated a more solid diet (p<0.001, gastric outlet obstruction scoring system). Twelve of 17 (71%) patients gained a median of 1.5 kg of body weight (p=0.001). The median Karnofsky scale increased from 50% to 60% in 13 of 17 (77%) patients. Conclusions: Self-expandable metallic stents are a safe, efficacious, and minimally invasive treatment option for palliation of patients with duodenal obstruction from biliary tract cancer. Technical complications can be managed endoscopically and the bile duct remains accessible for endoluminal treatment.

We demonstrate the use of Lee−Goldburg cross-polarization (LG-CP) NMR under fast magic-angle spinning (MAS) to investigate the amplitude and geometry of segmental motions in biomolecular and polymeric solids. Motional geometry information was previously available only from ²H NMR, which, however, has limited site resolution and requires site-specific isotopic labeling. Using a 2D LG-CP technique, we resolve the ¹³C−¹H or ¹⁵N−¹H dipolar couplings according to the ¹³C or ¹⁵N isotropic chemical shift. Applications to systems undergoing 180° phenylene ring flips show spectral line shapes reflecting the geometry of the motion. Using this LG-CP technique, we measured the ¹³C−¹H and ¹⁵N−¹H dipolar couplings in the water-soluble and membrane-bound states of the colicin Ia channel domain. The backbone motions of the membrane-bound colicin scale both the Cα−Hα and N−H couplings similarly, thus ruling out rotation of the α-helices around their axes as a specific mechanism of motion. We also show that the sensitivity of the LG-CP spectra can be enhanced by the addition of a phase-inverted ¹H−¹³C cross-polarization step, and the site resolution of the ¹⁵N−¹H LG-CP spectra can be enhanced by ¹³C indirect detection.

A combined solid-state NMR and small-angle X-ray scattering approach was employed to investigate morphology and lateral packing properties of mixed zwitterionic and cationic lipid membranes in the presence of an anionic polyelectrolyte. Binary mixtures of zwitterionic DMPC and cationic DODAP form stable lipid bilayers over a wide range of mixing ratios. Addition of negatively charged dextran sulfate (DS) leads to the formation of densely packed lipid bilayer stacks with the polyelectrolyte sandwiched between opposing lipid surfaces. Bridging of polyelectrolyte strands between bilayer surfaces provides attractive forces to overcompensate electrostatic and hydration repulsion, resulting in close approach of apposing membranes. The equilibrium surface distance is controlled by a balance of electrostatic, hydration, bridging, and entropic forces. Lipid molecules in the mixed membranes remain homogeneously distributed in both the absence and presence of DS. DS binds exclusively to cationic DODAP. As a result of DS binding, lipid chain order is equally increased throughout the lipid bilayer. Therefore, a partial penetration of the polyelectrolyte into the hydrophobic core of the membrane is unlikely. Increased order parameters correspond to a reduction of lateral lipid packing density equivalent to an average reduction of area per molecule of 2.9 Ų. We suggest that this area reduction is the result of membrane surface dehydration induced by the polyelectrolyte that creates attractive forces between bilayers.

The cross-peaks between lipid resonances in two-dimensional nuclear Overhauser enhancement spectroscopy ¹H NMR spectra, recorded with magic-angle spinning, contain valuable information about the structure and dynamics of the lipid bilayer. We have attempted a quantitative analysis of magnetization exchange between lipid resonances in the biologically relevant liquid crystalline lamellar phase. Spectra of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) water dispersions were recorded at mixing times from 0.005 to 1 s, and all diagonal and cross-peak volumes were determined by integration. The full relaxation-rate matrix was computed for the 10 lipid resonances by a matrix equation algorithm. Results of this mathematically rigorous approach were compared with simplified approaches to calculate cross-relaxation rates. In a second series of experiments, the DMPC was mixed with increasing amounts of perdeuterated DMPC-d67 to determine the percentage of intra- vs intermolecular magnetization transfer. With the exception of transfer between nearest neighbor protons by chemical bond, cross-relaxation in DMPC bilayers is exclusively intermolecular. There is no evidence for the transfer of magnetization over several bonds within lipid molecules by spin diffusion. Lipids exist in multiple conformations with rapid transitions between them, and, therefore, cross-relaxation rates do not represent stable molecular arrangements with fixed distances. Instead, the cross-relaxation rates reflect the probability of close approach between protons of neighboring lipid molecules. We established experimentally that cross-relaxation rates are proportional to the statistical average of lateral lipid−lipid contacts in binary mixtures. The location of lipid segments along the bilayer normal is best described by a distribution function. Segments which are located at the same depth in the bilayer approach each other with higher probability and have higher rates of magnetization transfer, compared with groups which are, on average, more distant and approach each other less frequently. The per-proton intermolecular cross-relaxation rates vary over the bilayer by only 1 order of magnitude, indicating surprisingly high probabilities of close approach even between the most distant groups, like the choline methyl groups and the terminal methyl groups of hydrocarbon chains. The results reflect the high degree of lipid motional disorder and the substantial variations in location of neighboring lipid molecules.