Mid-term Results of Chimney and Periscope Grafts in Supra-aortic Branches in High Risk Patients.

PURPOSE: Report mid-term outcomes of thoracic endovascular aneurysm repair (TEVAR) with chimney and periscope grafts (CPG) in supra-aortic branches (SAB). METHODS: Retrospective analysis, from October 2009 to May 2014, of patients with aneurysms requiring TEVAR with zone 0/1/2 proximal landing in association with at least one CPG in the SAB. All patients were considered at high risk for conventional surgery. Peri-operative mortality and morbidity, retrograde type A dissection, maximum aortic transverse diameter (TD) and its post-operative evolution, endoleak, survival, freedom from cardiovascular re-interventions, and CPG freedom from occlusion during the follow-up were analysed. RESULTS: Forty-one patients (28.05% EuroScore II) with thoraco-abdominal aortic aneurysm (17%), arch aneurysm (39%), descending aneurysm (34%), and aneurysm extending from the arch to the visceral aorta (10%) were included. Fifteen (37%) patients were treated non-electively. Fifty-nine SABs were treated with the CPG technique: one, two, three, and four CPG were employed in 71%, 19%, 5%, and 5% of patients, respectively. The proximal landing was in zone 0 in 49% of patients, zone 1 in 17%, and zone 2 in 34%. Technical success was 95%. Peri-operative complications and neurological events were registered in six (14.6%) patients and there were 5 deaths (12%). At a median follow-up of 21.2 (mean 22, SD 18; range 0-65) months, type I/III endoleaks were registered in three (7%) cases and re-intervention in six (15%) patients. A significant aneurysm sac shrinkage (p<.001) was reported at mean follow-up and no significant aneurysm sac increase (>5 mm). The estimated 2 year survival, freedom from re-intervention, freedom from endoleak, and freedom from branch occlusion were 75%, 77%, 86%, and 96%, respectively. CONCLUSION: The chimney and periscope grafts technique was shown to be safe in aortic aneurysm disease involving the supra aortic branches, even in an emergency setting using off the shelf devices. Mid-term follow-up results in this high risk population are good, but longer follow-up is mandatory before this technique is used in intermediate-risk patients.

Nuclear charge radii of (21-32)Mg.

Charge radii of all magnesium isotopes in the sd shell have been measured, revealing evolution of the nuclear shape throughout two prominent regions of assumed deformation centered on (24)Mg and (32)Mg. A striking correspondence is found between the nuclear charge radius and the neutron shell structure. The importance of cluster configurations towards N=8 and collectivity near N=20 is discussed in the framework of the fermionic molecular dynamics model. These essential results have been made possible by the first application of laser-induced nuclear orientation for isotope shift measurements.

Nuclear charge radius of 12Be.

The nuclear charge radius of (12)Be was precisely determined using the technique of collinear laser spectroscopy on the 2s(1/2)→2p(1/2,3/2) transition in the Be(+) ion. The mean square charge radius increases from (10)Be to (12)Be by δ(10,12)=0.69(5) fm(2) compared to δ(10,11)=0.49(5) fm(2) for the one-neutron halo isotope ^{11}Be. Calculations in the fermionic molecular dynamics approach show a strong sensitivity of the charge radius to the structure of ^{12}Be. The experimental charge radius is consistent with a breakdown of the N=8 shell closure.

Pair decay width of the Hoyle state and its role for stellar carbon production.

The pair decay width of the first excited 0+ state in 12C (the Hoyle state) is deduced from a novel analysis of the world data on inelastic electron scattering covering a wide momentum transfer range, thereby resolving previous discrepancies. The extracted value Γπ=(62.3±2.0) µeV is independently confirmed by new data at low momentum transfers measured at the S-DALINAC and reduces the uncertainty of the literature values by more than a factor of 3. A precise knowledge of Γπ is mandatory for quantitative studies of some key issues in the modeling of supernovae and of asymptotic giant branch stars, the most likely site of the slow-neutron nucleosynthesis process.

Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro.

Acute lung injury is a common complication in critically ill patients. The present study examined possible immunomodulating effects of the volatile anaesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro. Sevoflurane was applied after the onset of injury, simulating a "postconditioning" scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4-h co-exposure to a CO(2)/air mixture with sevoflurane 2.2 volume %; control cells were exposed to the CO(2)/air mixture only. Cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, as well as the potential protective mediators inducible nitric oxide synthase (iNOS)2 and heat shock protein (HSP)-32, were analysed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed. A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32. The data presented in the current study provide strong evidence that anaesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of acute lung injury.

Hypoxia attenuates effector-target cell interaction in the airway and pulmonary vascular compartment.

Leucocyte infiltration is known to play an important role in hypoxia-induced tissue damage. However, little information is available about hypoxia and interaction of effector (neutrophils) with target cells (alveolar epithelial cells, AEC; rat pulmonary artery endothelial cells, RPAEC). The goal of this study was to elucidate hypoxia-induced changes of effector-target cell interaction. AEC and RPAEC were exposed to 5% oxygen for 2-6 h. Intercellular adhesion molecule-1 (ICAM-1) expression was determined and cell adherence as well as cytotoxicity assays were performed. Nitric oxide and heat shock protein 70 (HSP70) production was assessed in target cells. Under hypoxic conditions enhanced ICAM-1 production was found in both cell types. This resulted in an increase of adherent neutrophils to AEC and RPAEC. The death rate of hypoxia-exposed target cells decreased significantly in comparison to control cells. Nitric oxide (NO) concentration was enhanced, as was production of HSP70 in AEC. Blocking NO production in target cells resulted in increased cytotoxicity in AEC and RPAEC. This study shows for the first time that target cells are more resistant to effector cells under hypoxia, suggesting hypoxia-induced cell protection. An underlying mechanism for this phenomenon might be the protective effect of increased levels of NO in target cells.

Effects of antileukemia agents on nuclear matrix-bound DNA replication in CCRF-CEM leukemia cells.

The effects of various antileukemic agents on DNA replication associated with the nuclear matrix were investigated in CCRF-CEM leukemia cells. Residual nuclear matrices were prepared by sequential treatment of nuclei with 1.5 M NaCl, DNase I, and Triton X-100 and contained 1-5, 10, and 37% of the total nuclear DNA, protein, and phospholipid, respectively. In control cells pulse-labeled for 45 s with [3H]thymidine, the specific activity of nascent DNA was four-fold greater in the nuclear matrix fraction relative to the specific activity of the high salt-soluble (nonmatrix) DNA fraction. Pulse-labeling and reconstitution experiments indicated that this enrichment of newly replicated DNA on the nuclear matrix did not result from aggregation of nascent DNA with the matrix. A 2-h incubation of tumor cells with either 0.1 microM teniposide (VM-26), 0.2 microM VM-26, or 0.5 microM amsacrine (m-AMSA) reduced the relative specific activity of nascent DNA on the nuclear matrix by 59, 61, and 54%, respectively, compared to control cells. In contrast hydroxyurea and cytosine arabinoside, at concentrations that markedly inhibited total nuclear DNA synthesis, did not decrease the relative specific activity of newly replicated DNA on the matrix. The results provide evidence that the antiproliferative effects of the DNA topoisomerase II inhibitors, VM-26 and m-AMSA, are localized on the nuclear matrix of CCRF-CEM leukemia cells.

Dynamical phase diagram of Gaussian wave packets in optical lattices.

We study the dynamics of self-trapping in Bose-Einstein condensates (BECs) loaded in deep optical lattices with Gaussian initial conditions, when the dynamics is well described by the discrete nonlinear Schrödinger equation (DNLSE). In the literature an approximate dynamical phase diagram based on a variational approach was introduced to distinguish different dynamical regimes: diffusion, self-trapping, and moving breathers. However, we find that the actual DNLSE dynamics shows a completely different diagram than the variational prediction. We calculate numerically a detailed dynamical phase diagram accurately describing the different dynamical regimes. It exhibits a complex structure that can readily be tested in current experiments in BECs in optical lattices and in optical waveguide arrays. Moreover, we derive an explicit theoretical estimate for the transition to self-trapping in excellent agreement with our numerical findings, which may be a valuable guide as well for future studies on a quantum dynamical phase diagram based on the Bose-Hubbard Hamiltonian.

An optimized workflow for the integration of biological information into radiotherapy planning: experiences with T1w DCE-MRI.

Planning of radiotherapy is often difficult due to restrictions on morphological images. New imaging techniques enable the integration of biological information into treatment planning and help to improve the detection of vital and aggressive tumour areas. This might improve clinical outcome. However, nowadays morphological data sets are still the gold standard in the planning of radiotherapy. In this paper, we introduce an in-house software platform enabling us to combine images from different imaging modalities yielding biological and morphological information in a workflow driven approach. This is demonstrated for the combination of morphological CT, MRI, functional DCE-MRI and PET data. Data of patients with a tumour of the prostate and with a meningioma were examined with DCE-MRI by applying pharmacokinetic two-compartment models for post-processing. The results were compared with the clinical plans for radiation therapy. Generated parameter maps give additional information about tumour spread, which can be incorporated in the definition of safety margins.

Oral theophylline intoxication. A serious error of patient and physician understanding.

Twenty-two episodes of hospitalization for patients with inadvertent oral theophylline intoxication were reviewed to determine the mechanism of toxicity as well as clinical features and pharmacokinetic values. Toxic effects occurred in older subjects with poorly reversible airflow obstruction and evidence of reduced theophylline clearance. Maximum serum theophylline levels ranged from 22.4 to 104.8 mg/L. Gastrointestinal tract disturbances were the most common toxic effects; three patients had grand mal seizures. Serum theophylline levels were a poor predictor of serious toxic effects. Causes of theophylline intoxication included excessive drug ingestion by the patient, excessive dose prescription by the physician, and unrecognized drug interactions. With appropriate patient selection and education, as well as better understanding of theophylline kinetics and potential drug interactions, inadvertent oral theophylline intoxication can be minimized.

Outpatient oxygen therapy in chronic obstructive pulmonary disease. A review of 13 years' experience and an evaluation of modes of therapy.

Thirteen years' experience with home oxygen for patients with advanced chronic obstructive pulmonary disease are reviewed. Home oxygen is safe and relieves pulmonary hypertension and elevated RBC mass in some, but not all patients. Marked clinical improvement is the most important result of long-term home oxygen use, including reduced hospitalizations and return to gainful employment for a few patients. Chronic compensated carbon dioxide retention is well tolerated and adaptive in cases of severe chronic airflow obstruction. New oxygen concentrators are effective in correcting hypoxemia and may make home oxygen administration more convenient and less expensive.

Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine.

Genes that confer cellular resistance to cytotoxic agents have potential applications both for marrow protection following cancer chemotherapy and as dominant selectable markers for the selection of genetically modified hematopoietic cell populations in vivo. Cytidine analogues, including cytosine arabinoside (Ara-C), 2',2'-difluorodeoxycytidine (gemcitabine), and other drugs represent a clinically important class of chemotherapeutic agents for which no drug resistance gene has yet been described. Studies were performed to determine whether forced expression of a gene encoding the enzyme cytidine deaminase can confer resistance to cytosine arabinoside (Ara-C) and gemcitabine in vitro. A pooled population of NIH3T3 cells overexpressing cytidine deaminase from a retroviral construct based on the LXSN-vector (LCDSN) demonstrated a 4.5-fold increased resistance to Ara-C based on the 50% inhibitory concentration (ID50) and a 3.7-fold increased resistance to Ara-C based on the 80% inhibitory concentration (ID80) relative to cells transduced with a control vector. In the hemopoietic cell line CCRF-CEM, the same retroviral construct conferred a 2.1-fold increased resistance to Ara-C by ID50 and a 3.0-fold increased resistance to Ara-C by ID80 relative to cells transduced with a control vector. CEM cells transduced with LCDSN were also resistant to gemcitabine (2.4-fold by ID50 and 2.5-fold by ID80). Furthermore, Ara-C-resistance could be completely reversed in LCDSN-transduced CEM cells by a specific inhibitor of cytidine deaminase, tetrahydrouridine (THU). Expression of the transgene was confirmed by RNase-protection assay and by an enzyme activity assay. These results provide the first direct evidence that forced expression of cytidine deaminase confers cellular resistance to Ara-C and gemcitabine.

Marrow sensitization to 5-fluorouracil using the ligands for Flt-3 and c-Kit.

In vivo administration of c-kit ligand (KL) expands early hemopoietic progenitors and stem cells and sensitizes clonogenic progenitors to 5-FU-mediated cell death. Studies were performed to determine whether the in vivo administration of Flk-2/Flt-3 ligand (FL) is also capable of sensitizing progenitors to 5-FU. Mice were treated with FL (100 micrograms/kg every 12 hours for a total of 3 doses), KL (50 micrograms/kg, same schedule) or both, either alone or in combination with 5-FU (a single 125 mg/kg injection 3 hours before the last dose of cytokine). Femurs and spleens were harvested 48 hours following the last dose of cytokine, and the total numbers of mononuclear cells and colony forming unit cells (CFU-C) per femur and spleen were determined. Statistically significant increases in the number of CFU-C per femur were observed in response to FL, KL and FL + KL. In the spleen, statistically significant increases in CFU-C were observed only with the FL + KL combination. 5-FU alone produced marked reductions in CFU-C both in the femur and in the spleen. In the femur, 5-FU-mediated reductions in CFU-C were enhanced 3- to 30-fold in the presence of concomitant KL, FL or KL + FL administration. Surprisingly, the combination of KL + FL was no more effective in sensitizing marrow CFU-C to 5-FU than was KL alone, suggesting that CFU-C that are capable of surviving the KL/5-FU combination cannot be driven into cell cycle by FL. The effects of concomitant cytokine/5-FU administration in the spleen contrasted sharply with those observed in the femur, as FL, KL and FL + KL all failed to enhance 5-FU-mediated reductions in CFU-C. The ability of FL + KL to stimulate CFU-C expansion in the spleen combined with the inability of this cytokine combination to augment 5-FU-mediated progenitor toxicity in the spleen supports the contention that cytokine-mobilized progenitors are not in cycle. FL's capacity to specifically sensitize marrow to the effects of cytotoxic drugs may have applications in bone marrow transplant conditioning regimens.

The hematological effects of folate analogs: implications for using the dihydrofolate reductase gene for in vivo selection.

Previous studies have shown that dihydrofolate reductase (DHFR) gene transfer protects marrow from methotrexate (MTX)-mediated toxicity; however, MTX treatment in vivo has not convincingly been shown to enrich DHFR-transduced progenitors or stem cells. Experiments were performed to better characterize the hematological effects of MTX, and maneuvers were tested with the aim of improving the utility of MTX as an agent for in vivo selection. Progenitors were assayed as colony forming unit cells in culture (CFU-C) and in the spleens of irradiated mice (day 11 CFU-S). A single injection of MTX at doses up to 250 mg/kg (more than three times the LD10) failed to reduce CFU-C numbers significantly in the femur or spleen assayed 1-3 days later. However, consistent declines in the number of mononuclear cells per femur reflected a significant depletion of nonclonogenic precursor cells. Preceding administration of pegylated stem cell factor (SCF), 100 micrograms/kg per day, increased CFU-C killing by a single dose of 5-fluorouracil (5-FU) 15- to 65-fold in the femur, and 5- to 15-fold in the spleen, consistent with previous reports. In contrast, despite preceding SCF administration there was no significant progenitor killing by MTX. Similar results were obtained using a second folate analog, trimetrexate. These results suggest that the mechanism by which folate analogs exert their hematological toxicity is through the depletion of relatively mature, nonclonogenic precursor cells, and not by killing progenitors. This information is relevant to the use of DHFR in gene therapy protocols, and suggests that folate analogs are poorly suited agents for selection at the level of clonogenic progenitor cells in vivo.

Diffuse alveolar hemorrhage due to antibasement membrane antibody disease appearing with a polyglandular autoimmune syndrome.

We describe a patient with type 3-C polyglandular autoimmune syndrome who presented with diffuse alveolar hemorrhage and normal renal function. The diagnosis of antibasement membrane antibody disease was established by immunofluorescent staining of transbronchial biopsy specimens. We suggest the incorporation of antibasement membrane antibody disease into the spectrum of diseases that define the polyglandular autoimmune syndromes.

Prone postioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS.

STUDY OBJECTIVES: Investigating the effect of low-volume pressure-limited ventilation and repeated prone positioning on the short-term course and outcome in patients with severe ARDS. SETTING: Level 1 trauma center of a university hospital. PATIENTS: Twenty-five patients suffering from ARDS with a lung injury score (LIS) > or = 2.5 admitted consecutively to our ICU from January 1992 to December 1994. METHODS: Mechanical ventilation with peak inspiratory pressure limitation to 35 mbar, irrespective of hypercapnia and prone positioning to achieve adequate oxygenation. SCORING AND MEASUREMENTS: Patient assessment with LIS, APACHE (acute physiology and chronic health evaluation) II score, injury severity score, and multiple organ failure score. Blood gas analyses and estimation of static compliance were repeated at least every 4 h during the treatment period. PaO2/FIO2 (fraction of inspired oxygen) ratio, alveolo-arterial oxygen difference, and intrapulmonary shunt were calculated according to standard equations. The best values taken from each 4-h period during the investigation were used to evaluate the best possible performance of the lung within this interval and to investigate the entire course. RESULTS: Mean predicted mortality based on the APACHE II score was 35.4+/-15.2%. Three of the 25 patients (12%) died. However, none was related to respiratory failure. No pneumothorax occurred. Sixteen patients, lacking any contraindication for prone positioning, responded positively to this change in position, each to a different individual degree. CONCLUSION: We assume that our low mortality in patients with severe ARDS might be due mainly to low-volume pressure-limited ventilation and prone positioning. This simple strategy seems to allow successful treatment for patients with severe ARDS.

Demand and continuous flow intermittent mandatory ventilation systems.

A mechanical lung was used to evaluate the pressure and flow characteristics of four demand and two continuous flow intermittent mandatory ventilation (IMV) systems. The amount of negative pressure required to initiate inspiratory flow and peak expiratory resistance were measured. The inspiratory pressure required to initiate flow in the demand mode was also compared to pressures generated in the assist mode. In addition, the peak expiratory resistance was measured with four commercially available exhalation valves. Results showed that the ventilator manometer measuring internal machine pressures significantly underestimated the amount of negative pressure required to open the demand valve (p less than 0.01). There are major differences in the flow and pressure characteristics among demand and continuous flow IMV systems. Systems that impose high inspiratory elastic threshold loads and expiratory flow resistive loads may have a deleterious effect on the mechanics of breathing, and thereby limit weaning success and eventually impair the recovery of certain patients in respiratory failure. The basic methodology, especially the simple technique of inserting an aneroid manometer in line next to a patient's ET tube, for measuring proximal negative inspiratory force (NIF test) can be easily applied to any and all ventilators at any practitioner's individual institution.

Influence of infusion line compliance on drug delivery rate during acute line loop formation.

OBJECTIVE: To determine whether infusion line compliance contributes to irregular drug delivery during vertical displacement of syringe pumps. DESIGN: Five different commercially available infusion lines were studied at infusion rates of 0.5, 1.0, and 1.5 ml/h. Zero drug delivery time was measured after acute line loop formation (70 cm) using an electronic balance. Compliance of each infusion line was calculated using a pressure transducer and measurement of the occlusion release bolus at 300 mmHg occlusion pressure. Finally, the influence of infusion line compliance on drug delivery during acute lowering of the syringe pump was studied using low- and high-compliance infusion lines. RESULTS: Acute line loop formation resulted in zero drug delivery time from 5.1 +/- 1.5 to 44.0 +/- 6.8 s at flow rates of 0.5 ml/h. Increased flow rates significantly reduced loop-induced flow variability. A close correlation was found between zero drug delivery time and calculated infusion line compliance at 0.5 ml/h (linear regression R2 = 0.79). Lowering of the syringe pump 50 cm prolonged zero drug delivery time from 295.8 +/- 20.7 s with the low-compliance tube to 463.3 +/- 24.0 s with the high-compliance infusion line. CONCLUSIONS: Infusion line compliance contributes to irregular drug delivery associated with vertical displacement of syringe pumps. Siphoning of the infusion line during patient care should be avoided, and flow rates of 1 ml/h or higher are recommended. Low-compliance infusion lines are indicated whenever highly short-acting vasoactive drugs at low delivery rates are administered.

Infusion pump performance with vertical displacement: effect of syringe pump and assembly type.

OBJECTIVE: To evaluate the effect of different infusion pump models on continuity of drug delivery during vertical displacement of syringe pumps. DESIGN: Zero-drug delivery time (ZDDT), retrograde aspiration volume, and infusion bolus were recorded using the same syringe in three different models of syringe pump after lowering and elevating the pump. Compliance of each infusion assembly was measured using the occlusion release technique at 38 mmHg. RESULTS: Lowering the pump by 50 cm at an infusion rate of 1 ml/h resulted in ZDDT values ranging from 2.78 +/- 0.29 to 5.99 +/- 1.09 min. Elevating the syringe pump to its original position caused infusion boluses between 44.1 +/- 3.2 and 77.1 +/- 5.1 microl. The results demonstrated that there are large differences between syringe pump models (F = 66.8, df = 2/33, p < 0.0001) and between pumps of the same model (F = 21.3, df = 1/34, p < 0.0001). A similar pattern was found in retrograde aspiration volume and infusion bolus. CONCLUSION: All tested pumps led to clinically relevant flow irregularities during vertical displacement of the syringe pump. Thus, vertical displacement of any syringe pump connected to an infusion line delivering highly potent drugs at low infusion rates should be avoided. The variability across syringe pumps indicates that syringe pump design remains an area of potential further improvement for reducing the risk of adverse patient events.

Primary hypothyroidism associated with multicystic ovaries and ovarian torsion in an adult.

BACKGROUND: Primary hypothyroidism is known to be associated with multicystic ovaries in juvenile females, but this association has been reported only once previously in an adult. This report describes an unusual case of bilateral multicystic ovaries occurring in an adult patient with profound hypothyroidism. CASE: A 26-year-old woman presented with an acute abdomen and bilateral adnexal masses. An emergency exploratory laparotomy revealed bilateral enlarged multicystic ovaries with torsion of the right ovary. Because this ovary was necrotic, it was removed; pathology revealed multiple hemorrhagic follicular cysts. Laboratory studies to evaluate the cause of the multicystic ovaries revealed negative serum beta-hCG, LH 0.7 IU/L, FSH 15.7 IU/L, and estradiol 80 pg/mL. The TSH value was greater than 50 IU/L and serum thyroxine was undetectable, demonstrating profound hypothyroidism. Subsequent thyroid hormone replacement was associated with resolution of the cysts in the remaining ovary. CONCLUSION: Profound hypothyroidism can cause multicystic ovaries in an adult. In the absence of ovarian torsion, surgery can be avoided, as thyroid hormone replacement leads to clinical resolution of the cysts within 3 months.