Fetal Monitoring of Patients Diagnosed with Systemic Lupus Erythematosus - A Case Report.

We report a case of pathological foetal Doppler velocity, specifically the absence of end diastolic flow in the umbilical artery (AEDV/REDV), suspected diabetic pregnancy and mesangioproliferative glomerulonephritis, at 32 weeks of gestation. The foetal heart rate tracings were evaluated using a computerised cardiotocogram (Oxford Sonicaid system 8002 Chichester, England) 1 for 20-30 min parallel to the routine cardiotocogram. The ultrasound control at 33 weeks of gestation showed oligohydramnion, foetal centralisation and reduced interval foetal growth. Due to small gestational age (SGA) and oligohydramnion, labour was induced at 36 weeks gestation with vaginal prostaglandin and an amniotomy. Due to cephalopelvic disproportion, a Caesarean section was performed. Signs and symptoms of neonatal lupus were not found.

Coherence properties of nanofiber-trapped cesium atoms.

We experimentally study the ground state coherence properties of cesium atoms in a nanofiber-based two-color dipole trap, localized ∼ 200 nm away from the fiber surface. Using microwave radiation to coherently drive the clock transition, we record Ramsey fringes as well as spin echo signals and infer a reversible dephasing time of T(2)(*) = 0.6 ms and an irreversible dephasing time of T(2)(') = 3.7 ms. By modeling the signals, we find that, for our experimental parameters, T(2)(*) and T(2)(') are limited by the finite initial temperature of the atomic ensemble and the heating rate, respectively. Our results represent a fundamental step towards establishing nanofiber-based traps for cold atoms as a building block in an optical fiber quantum network.

Haemobilia following blunt liver injury.

Blunt liver trauma is commonly managed by non-operative measures. We report a case of an American Association for the Surgery of Trauma grade III liver injury and its complications, successfully managed by a combination of minimally invasive interventions.

Dispersive optical interface based on nanofiber-trapped atoms.

We dispersively interface an ensemble of 1000 atoms trapped in the evanescent field surrounding a tapered optical nanofiber. This method relies on the azimuthally asymmetric coupling of the ensemble with the evanescent field of an off-resonant probe beam, transmitted through the nanofiber. The resulting birefringence and dispersion are significant; we observe a phase shift per atom of ∼1 mrad at a detuning of 6 times the natural linewidth, corresponding to an effective resonant optical density per atom of 0.027. Moreover, we utilize this strong dispersion to nondestructively determine the number of atoms.

Observation of nuclear-spin Seebeck effect.

Thermoelectric effects have been applied to power generators and temperature sensors that convert waste heat into electricity. The effects, however, have been limited to electrons to occur, and inevitably disappear at low temperatures due to electronic entropy quenching. Here, we report thermoelectric generation caused by nuclear spins in a solid: nuclear-spin Seebeck effect. The sample is a magnetically ordered material MnCO3 having a large nuclear spin (I = 5/2) of 55Mn nuclei and strong hyperfine coupling, with a Pt contact. In the system, we observe low-temperature thermoelectric signals down to 100 mK due to nuclear-spin excitation. Our theoretical calculation in which interfacial Korringa process is taken into consideration quantitatively reproduces the results. The nuclear thermoelectric effect demonstrated here offers a way for exploring thermoelectric science and technologies at ultralow temperatures.

Optical interface created by laser-cooled atoms trapped in the evanescent field surrounding an optical nanofiber.

Trapping and optically interfacing laser-cooled neutral atoms are essential requirements for their use in advanced quantum technologies. Here we simultaneously realize both of these tasks with cesium atoms interacting with a multicolor evanescent field surrounding an optical nanofiber. The atoms are localized in a one-dimensional optical lattice about 200 nm above the nanofiber surface and can be efficiently interrogated with a resonant light field sent through the nanofiber. Our technique opens the route towards the direct integration of laser-cooled atomic ensembles within fiber networks, an important prerequisite for large scale quantum communication schemes. Moreover, it is ideally suited to the realization of hybrid quantum systems that combine atoms with, e.g., solid state quantum devices.

Stability and reproducibility of 6013 deep inspiration breath-holds in left-sided breast cancer.

PURPOSE: Patients with left-sided breast cancer frequently receive deep inspiration breath-hold (DIBH) radiotherapy to reduce the risk of cardiac side effects. The aim of the present study was to analyze intra-breath-hold stability and inter-fraction breath-hold reproducibility in clinical practice. MATERIAL AND METHODS: Overall, we analyzed 103 patients receiving left-sided breast cancer radiotherapy using a surface-guided DIBH technique. During each treatment session the vertical motion of the patient was continuously measured by a surface guided radiation therapy (SGRT) system and automated gating control (beam on/off) was performed using an audio-visual patient feedback system. Dose delivery was automatically triggered when the tracking point was within a predefined gating window. Intra-breath-hold stability and inter-fraction reproducibility across all fractions of the entire treatment course were analyzed per patient. RESULTS: In the present series, 6013 breath-holds during beam-on time were analyzed. The mean amplitude of the gating window from the baseline breathing curve (maximum expiration during free breathing) was 15.8 mm (95%-confidence interval: [8.5-30.6] mm) and had a width of 3.5 mm (95%-CI: [2-4.3] mm). As a measure of intra-breath-hold stability, the median standard deviation of the breath-hold level during DIBH was 0.3 mm (95%-CI: [0.1-0.9] mm). Similarly, the median absolute intra-breath-hold linear amplitude deviation was 0.4 mm (95%-CI: [0.01-2.1] mm). Reproducibility testing showed good inter-fractional reliability, as the maximum difference in the breathing amplitudes in all patients and all fractions were 1.3 mm on average (95%-CI: [0.5-2.6] mm). CONCLUSION: The clinical integration of an optical surface scanner enables a stable and reliable DIBH treatment delivery during SGRT for left-sided breast cancer in clinical routine.

Real-time intra-fraction motion management in breast cancer radiotherapy: analysis of 2028 treatment sessions.

BACKGROUND: Intra-fraction motion represents a crucial issue in the era of precise radiotherapy in several settings, including breast irradiation. To date, only few data exist on real-time measured intra-fraction motion in breast cancer patients. Continuous surface imaging using visible light offers the capability to monitor patient movements in three-dimensional space without any additional radiation exposure. The aim of the present study was to quantify the uncertainties of possible intra-fractional motion during breast radiotherapy. MATERIAL AND METHODS: One hundred and four consecutive patients that underwent postoperative radiotherapy following breast conserving surgery or mastectomy were prospectively evaluated during 2028 treatment sessions. During each treatment session the patients' motion was continuously measured using the Catalyst™ optical surface scanner (C-RAD AB, Sweden) and compared to a reference scan acquired at the beginning of each session. The Catalyst system works through an optical surface imaging with light emitting diode (LED) light and reprojection captured by a charge coupled device (CCD) camera, which provide target position control during treatment delivery with a motion detection accuracy of 0.5 mm. For 3D surface reconstruction, the system uses a non-rigid body algorithm to calculate the distance between the surface and the isocentre and using the principle of optical triangulation. Three-dimensional deviations and relative position differences during the whole treatment fraction were calculated by the system and analyzed statistically. RESULTS: Overall, the maximum magnitude of the deviation vector showed a mean change of 1.93 mm ± 1.14 mm (standard deviation [SD]) (95%-confidence interval: [0.48-4.65] mm) and a median change of 1.63 mm during dose application (beam-on time only). Along the lateral and longitudinal axis changes were quite similar (0.18 mm ± 1.06 mm vs. 0.17 mm ± 1.32 mm), on the vertical axis the mean change was 0.68 mm ± 1.53 mm. The mean treatment session time was 154 ± 53 (SD) seconds and the mean beam-on time only was 55 ± 16 s. According to Friedman's test differences in the distributions of the three possible directions (lateral, longitudinal and vertical) were significant (p < 0.01), in post-hoc analysis there were no similarities between any two of the three directions. CONCLUSION: The optical surface imaging system is an accurate and easy tool for real-time motion management in breast cancer radiotherapy. Intra-fraction motion was reported within five millimeters in all directions. Thus, intra-fraction motion in our series of 2028 treatment sessions seems to be of minor clinical relevance in postoperative radiotherapy of breast cancer.

Optical Surface Scanning for Patient Positioning in Radiation Therapy: A Prospective Analysis of 1902 Fractions.

PURPOSE/OBJECTIVE: Reproducible patient positioning remains one of the major challenges in modern radiation therapy. Recently, optical surface scanners have been introduced into clinical practice in addition to well-established positioning systems, such as room laser and skin marks. The aim of this prospective study was to evaluate setup errors of the optical surface scanner Catalyst HD (C-RAD AB) in different anatomic regions. MATERIAL/METHODS: Between October 2016 and June 2017 a total of 1902 treatment sessions in 110 patients were evaluated. The workflow of this study included conventional setup procedures using laser-based positioning with skin marks and an additional registration of the 3-dimensional (3D) deviations detected by the Catalyst system. The deviations of the surface-based method were then compared to the corrections of cone beam computed tomography alignment which was considered as gold standard. A practical Catalyst setup error was calculated between the translational deviations of the surface scanner and the laser positioning. Two one-sided t tests for equivalence were used for statistical analysis. RESULTS: Data analysis revealed total deviations of 0.09 mm ± 2.03 mm for the lateral axis, 0.07 mm ± 3.21 mm for the longitudinal axis, and 0.44 mm ± 3.08 mm vertical axis for the Catalyst system, compared to -0.06 ± 3.54 mm lateral, 0.53 ± 3.47 mm longitudinal, and 0.19 ± 3.49 mm vertical for the laser positioning compared to cone beam computed tomography. The lowest positional deviations were found in the cranial region, and larger deviations occurred in the thoracic and abdominal sites. A statistical comparison using 2 one-sided t tests showed a general concordance of the 2 methods ( P ≤ 0.036), excluding the vertical direction of the abdominal region ( P = 0.198). CONCLUSION: The optical surface scanner Catalyst HD is a reliable and feasible patient positioning system without any additional radiation exposure. From the head to the thoracic and abdominal region, a decrease in accuracy was observed within a comparable range for Catalyst and laser-assisted positioning.

Central and peripheral actions of a nonpeptidic angiotensin II receptor antagonist.

Nonpeptidic imidazole derivatives were recently reported to be angiotensin II receptor antagonists with acute blood pressure-lowering activity. In the present study, we characterized the angiotensin II receptor antagonist properties of one such derivative, 4'-([2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl)- [1,1'-biphenyl]-2-carboxylic acid (IMI). In receptor binding studies, IMI displaced bound [125I]angiotensin II from rat uterine membranes with an IC50 of 0.17 microM. In isolated rabbit aortic rings, IMI shifted the angiotensin II concentration-response curve to the right in a parallel and concentration-dependent manner. A Schild plot of these data indicated a pA2 of 7.13 +/- 0.16 and a slope of 0.94 +/- 0.06. In rat kidney slices, IMI shifted the concentration-response curve for angiotensin II-induced inhibition of renin release to the right. Antagonism of the angiotensin II pressor response by IMI was dose dependent and reversible in ganglion-blocked, anesthetized rats. The water intake and pressor responses to intracerebroventricular angiotensin II (100 pmol) were inhibited by intracerebroventricular IMI (25 or 50 nmol) in conscious Sprague-Dawley rats. Similarly, the drinking and pressor responses to intravenous angiotensin II were blocked by intravenous IMI in conscious rats. IMI alone had no effects on mean arterial pressure or drinking when administered either intravenously or intracerebroventricularly. IMI decreased mean arterial pressure throughout 5 days of infusion in spontaneously hypertensive rats. In summary, IMI was a full competitive antagonist without partial agonist activity in peripheral tissues and the central nervous system. Moreover, the chronic administration of this angiotensin II receptor antagonist was antihypertensive in spontaneously hypertensive rats.

Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor antagonists.

2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl]-3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.

Nonpeptide angiotensin II antagonists: N-phenyl-1H-pyrrole derivatives are angiotensin II receptor antagonists.

A series of 5-[1-[4-[(4,5-disubstituted-1H-imidazol-1-yl)methyl]- substituted]-1H-pyrrol-2-yl]-1H-tetrazoles and 5-[1-[4-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-substituted]- 1H-pyrrol-2-yl]-1H-tetrazoles were investigated as novel AT1-selective angiotensin II receptor antagonists. Computer-assisted modeling techniques were used to evaluate structural parameters in comparison to the related biphenyl system. New synthetic procedures have been developed to prepare the novel compounds. The best antagonists in this series had IC50 values (rat uterine membrane receptor binding) in the 10(-8) M range and corresponding pA2 in isolated organ assay (rabbit aorta rings). Structure-activity relationships indicate some similarities with the finding in the biphenyl system. Substitution on the pyrrole ring modulates activity. Compound 5 antagonized angiotensin-induced blood pressure increase when administered to conscious rat at 30 mg/kg per os.

Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents.

A novel series of terphenyl methyl sulfones and sulfonamides have been shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely advantageous for both in vitro COX-2 potency and selectivity as well as in vivo activity. Several noticeable examples in the 1,2-diaryl-4,5-difluorobenzenesulfonamide series are 21a-c,k,l,n (COX-2, IC50 = 0.002-0.004 microM), in which all have in vitro COX-1/COX-2 selectivity > 1000. In addition, sulfonamides 21a,b,d,g,j,m,n,q were shown to have greatly enhanced oral activity with more than 90% inhibition of prostaglandin E2 production in the air pouch model of inflammation. Furthermore, sulfonamide 21b was found to be very active in the rat adjuvant-induced arthritis model (ED50 = 0.05 mg/kg) and carrageenan-induced hyperalgesia assay (ED50 = 38.7 mg/kg) with no indication of gastrointestinal toxicity in rats at doses as high as 200 mg/kg.

Diarylspiro[2.4]heptenes as orally active, highly selective cyclooxygenase-2 inhibitors: synthesis and structure-activity relationships.

A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the 6-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity. Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.

In vivo pharmacology of SC-51316, a nonpeptidic angiotensin II receptor antagonist.

The depressor activity of a novel nonpeptidic angiotensin II (AII) receptor antagonist, SC-51316 (2,5-dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4 '- yl]-methyl]-3H-1,2,4-triazol-3-one), is described. In anesthetized, ganglion-blocked rats, intravenous administration of SC-51316 inhibited the pressor response to an infusion of AII. To determine antihypertensive efficacy, conscious, spontaneously hypertensive rats were administered SC-51316 (30 mg/kg intragastrically) daily for 5 days. Blood pressure was reduced in a similar manner to that observed with the angiotensin converting enzyme inhibitor enalapril (10 mg/kg intragastrically). SC-51316 had no effect on heart rate. In conscious, sodium-deficient dogs, administration of SC-51316 (30 mg/kg orally) or enalapril (10 mg/kg orally) lowered blood pressure similarly over a 24 h observation period. Thus, SC-51316 antagonizes the activity of AII in vivo and is an orally active, antihypertensive agent.

Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit.

Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor (PAI), D-dimer, euglobulin-clot-lysis-time (ECLT), plasminogen, alpha 2-antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II-score). An increase in D-dimer and t-PA-antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t-PA-activity was not detectable, PAI-function was elevated, the ECLT was prolonged and alpha 2-antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t-PA-antigen, PAI-function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II-score of the patients. We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, alpha 2-antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.

Electrophoresis and immunoblot of cerebrospinal fluid proteins in spasmodic torticollis.

Protein patterns of cerebrospinal fluid (CSF) from patients with spasmodic torticollis (ST) were investigated to determine whether abnormalities previously reported could be detected and further identified. CSF was collected from 12 patients with ST and 6 normal controls. The CSF proteins were analyzed using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and silver staining. In 11 of the 12 patients with ST, a CSF protein pattern was observed which differed from that in the controls. The identity of the abnormal proteins was ascertained by blotting and immunostaining with specific antisera to IgG and ceruloplasmin (Cp). CSF from 2 of 12 patients had distinct bands staining for IgG and 7 had abnormal immunostaining for Cp.

Comparison of methods for analysis of CSF proteins in patients with Alzheimer's disease.

Cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and controls was analyzed by one- and two-dimensional gel electrophoresis, electron microscopy, and fluorescence microscopy with thioflavin S staining. In CSF from patients with AD, abnormal proteins were found following two-dimensional gel electrophoresis and silver staining. In CSF samples from most of the AD patients studied, a highly argentophilic material was detected upon silver staining the stacking gel of the one-dimensional gels. Electron microscopy of material eluted from the stacking gel showed fibers of approximately 7-10 nm diameter, with some twisting; properties consistent with paired helical filaments or amyloid. Furthermore, material with the characteristics of amyloid (fiber diameter ranging from 4-10 nm) was found in the CSF sediment. The CSF from AD patients had significantly elevated numbers of yellow fluorescent particles following thioflavin S staining when compared with age-matched, other neurological disease controls. We did not see an increase in autofluorescence, indicating that thioflavin S staining is specific. Our data suggest that AD CSF contains plaque amyloid and possibly proteins from neurofibrillary tangles. The thioflavin S staining method appears to have potential for development as a diagnostic tool.