Bioconjugation of COL1 protein on liquid-like solid surfaces to study tumor invasion dynamics.

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.

Hypoxic respiratory failure in the late preterm infant.

Hypoxic respiratory failure in late preterm infants has received increased attention in the last decade, and while the incidence is low, it accounts for a significant number of admissions to neonatal ICUs because of the large number of late preterm births in the United States and worldwide. Causes of respiratory distress include transient tachypnea of the newborn, surfactant deficiency, pneumonia, and pulmonary hypertension. The physiologic mechanisms underlying delayed transition caused by surfactant deficiency and poor fetal lung fluid absorption have been reviewed recently elsewhere. This article focuses on the less-explored problem of severe hypoxic respiratory failure in the late preterm infant and discusses potential strategies for management.

Respiratory transition in infants delivered by cesarean section.

One of the biggest challenges a newborn faces after birth is the task of making a smooth transition to air breathing. This task is complicated by the fact that fetal lungs are full of fluid which must be cleared rapidly to allow for gas exchange. Respiratory morbidity as a result of failure to clear fetal lung fluid is not uncommon, and can be particularly problematic in some infants delivered by elective cesarean delivery (ECS). Given the high rates of cesarean deliveries in the USA and worldwide, the public health and economic impact of morbidity in this subgroup is considerable. Whereas the occurrence of birth asphyxia, trauma, and meconium aspiration is reduced by elective Cesarean delivery, the risk of respiratory distress secondary to transient tachypnea of the newborn, surfactant deficiency, and pulmonary hypertension is increased. It is clear that physiologic events in the last few weeks of pregnancy coupled with the onset of spontaneous labor are accompanied by changes in the hormonal milieu of the fetus and its mother, resulting in preparation of the fetus for neonatal transition. Rapid clearance of fetal lung fluid is a key part of these changes, and is mediated in large part by transepithelial Na reabsorption through amiloride-sensitive Na channels in the alveolar epithelial cells, with only a limited contribution from mechanical factors and Starling forces. This chapter discusses the physiologic mechanisms underlying fetal lung fluid absorption and explores potential strategies for facilitating neonatal transition when infants are delivered by ECS before the onset of spontaneous labor.

Clinical performance of an in-line, ex vivo point-of-care monitor: a multicenter study.

BACKGROUND: The management of critically ill infants and neonates includes frequent determination of arterial blood gas, electrolyte, and hematocrit values. An objective of attached point-of-care patient monitoring is to provide clinically relevant data without the adverse consequences associated with serial phlebotomy. METHODS: We prospectively determined the mean difference (and SD of the difference) from laboratory methods of an in-line, ex vivo monitor, the VIA LVM Blood Gas and Chemistry Monitoring System (VIA LVM Monitor; Metracor Technologies, Inc.), in 100 critically ill neonates and infants at seven children's hospitals. In doing so, we examined monitor stability with continuous use. In vivo patient test results from laboratory benchtop analyzers were compared with those from the VIA LVM Monitor on paired samples. In a separate in vitro comparison, benchtop analyzer and monitor test results were compared on whole-blood split samples. RESULTS: A total of 1414 concurrent, paired-sample measurements were obtained. The mean differences (SD of differences) from laboratory methods and r values for the combined data for the VIA LVM Monitor from the seven sites were 0.001 (0.026) and 0.97 for pH, 0.7 (3.6) mmHg and 0.94 for PCO(2), 4.2 (9.6) mmHg and 0.98 for PO(2), 0.0 (2.9) mmol/L and 0.87 for sodium, 0.1 (0.2) mmol/L and 0.96 for potassium, and 0.3% (2.9%) and 0.90 for hematocrit. Performance results were similar among the study sites with increasing time of monitor use and between in vivo paired-sample and in vitro split-sample test results. CONCLUSION: The VIA LVM Monitor can be used to assess critically ill neonates and infants.

[The use of an early postoperative interstitial-hyperthermia combination therapy in malignant gliomas]. / Einsatz einer früh postoperativen interstitiellen Hyperthermiekombinationstherapie bei malignen Gliomen.

BACKGROUND: The survival of people suffering from malignant gliomas (WHO level III and IV) is predominantly limited by local progress in the primary tumor region. Interstitial hyperthermia combined with radiotherapy or chemotherapy is one approach for the intensification of local therapy. It is possible to combine (partial) tumor resection with hyperthermia as well as with brachytherapy by implanting catheters intraoperatively. PATIENTS AND METHODS: A pilot study was performed to examine practicality, tolerability, effectiveness and scope for improvement in early postoperative hyperthermia treatment following catheter implantation as part of (partial) tumor resection. Each CT data set was transferred into a VAX 3100 workstation for retrospective analysis of the hyperthermia treatment. The implanted catheters were segmented and the distributions of power density and temperature were simulated. We sought to achieve the best possible temperature distributions by optimising the catheter arrangement in the planning calculations. The corresponding Ir-192-source brachytherapy treatments were simulated in a similar way using the implanted, as well as optimised catheter arrays. RESULTS: Intraoperative catheter implantation in 4 patients was problem-free. Postoperative complications were not observed, neither were infections. Interstitial microwave hyperthermia in combination with percutaneous irradiation or chemotherapy a few days after the operation was also tolerated well by all patients. Effective temperatures (of at least 42 degrees C) were regularly achieved at measurement points, but the temperature distributions were unsatisfactory, with T90 values (the temperature reached in at least 90% of the target volume) of under 38 degrees C. Measured temperature/position curves showed qualitative correlation with the simulated calculations. The catheter positions determined by optimisation varied significantly from the positions clinically used. CONCLUSIONS: Early postoperative combination therapy using hyperthermia for the treatment of malignant gliomas is a very practical approach. The optimisation strategies described should be used preoperatively to plan catheter arrays for interstitial hyperthermia and brachytherapy, and these arrays should be implanted using stereotaxic surgery.

Glucocorticoid-induced osteoporosis: a cross-sectional study.

We studied 70 patients (48 women and 22 men) with either rheumatic disease (n = 25) or lung disease (n = 45) who had been treated with glucocorticoids for at least 6 months (mean cumulative dose, 24.2 +/- 27.1 g of prednisone; mean current dose, 11.0 +/- 8.6 mg/d, mean duration of therapy, 8.1 years. We measured bone mineral density (BMD) of the hip (femoral neck) and spine (L2-L4) using dual-photon absorptiometry and BMD of the distal one third radius using single-photon absorptiometry. Compared with age-matched controls, the study population had decreased BMD of the spine (87.0%), hip (87.2%), and radius (90.6%). Current dose, cumulative dose, and duration of therapy were not correlated with BMD in the spine or hip in the total study population. The most significant correlations with low bone mass at the hip and spine were short height and low weight. There was a high incidence of hypercalciuria (30%) as compared with an age- and sex-matched control group (6.4%). Glucocorticoids are known to decrease vertebral and radial bone density. We conclude that glucocorticoids also decrease hip bone density as measured at the femoral neck. The high incidence of hypercalciuria may have implications for therapy of glucocorticoid-induced osteoporosis.

[Optimization of conditions for detecting density variations in focal activity in SPECT using the rotating gamma camera. Model calculations, phantom measurements and clinical applications]. / Optimierung der Nachweisbedingungen von fokalen Aktivitätsdichteschwankungen, in der SPECT mit der rotierenden Gammakamera. Modellrechnungen, Phantommessungen, klinische Anwendungen.

The signal to noise ratio (quotient of contrast and mean noise) is a quality parameter for identifying activity gaps during single photon emission computed tomography (SPECT). Contrast and mean noise level are site-dependent on the reconstruction plane which is influenced in a complex manner by absorption conditions (strong or weak absorption), modes of rotation (full angle or partial angle imaging), interdependencies of opposing partial projections (arithmetic or geometric mean), magnitude of defect (relative to the resolution of the imaging system), geometry of the object to be measured, and scatter. In the present study the authors performed analysis and graphical representation of the SPECT imaging properties on the basis of model calculations illustrated by phantom measurements. The optimal conditions of examination or evaluation and the diagnostic criteria in SPECT of the heart, liver, brain and pelvis are discussed by comparative calculation of signal to noise ratios in defect identification.

Pelvimetry by digital radiography and its dosimetry.

Sonography is firmly established in obstetrics as the method of choice for the localization of fetus and placenta. However, for the determination of pelvic dimensions sonography does not suffice. Thus, for a few strictly selected indications conventional x-ray pelvimetry is used. This has the disadvantage of the relatively high radiation dose for the fetus and the maternal gonads. Since the introduction of digital radiography, there is the alternative of digital pelvimetry. We performed dosimetry comparing digital and conventional radiography with the new high amplifying screens (Quanta III, Dupont) using an ionization dosimeter and a wax phantom. The radiation dose of digital radiography was 24 mu Gy. This corresponds to about 15% of a comparable conventional exposure (177 mu Gy). A further advantage of digital radiography is a standardized and rapid exposure technique; furthermore pelvic dimensions can be measured directly. The disadvantages are the poorer spacial resolution and poor image quality in obese patients. Digital radiography because of its lower radiation dose is suitable for pelvimetry for special indications.

[A computer model for the simulation of intra-arterial tumor therapy in the area of the external carotid artery]. / Ein Computer-Modell zur Simulation der intraarteriellen Tumortherapie im Bereich der A. carotis externa.

The complex theoretical background of intra-arterial (i.a.) tumour therapy induced the installation of a computer assisted model based on the use of 7 variables, the most important factors being the blood flow of the infused organ and the clearance of the drug, as well as the tissue binding of the drug. Various relevant conditions of i.a. infusion are represented by simple but typical diagrams allowing quick orientation on the principles governing i.a. infusion even for those who are not very familiar with the theoretical background of i.a. infusion. The model represents an improvement in the individual planning of effective i.a. chemotherapy.

[Radiation exposure of the examiner during digital subtraction angiography in the continuous-mode operation]. / Strahlenbelastung des Untersuchers bei der digitalen Subtraktionsangiographie im Continuous-mode-Verfahren.

The radiation dose exposure measured at the eye lens of the examinating radiologist has been determined for a digital subtraction angiographic unit by experimental registration. A radiation dose of 15 mSv per month could be registered.

Pharmacokinetics of intra-arterial tumour therapy. An experimental study.

Mathematically based pharmacokinetic models confirmed the general belief that intra-arterial (i.a.) cytostatic drug infusion can produce an increase in local tissue levels and a reduction in systemic drug availability. The increase in local drug concentration depends largely on the blood-flow rate of the infused artery and the rate of drug elimination from the rest of the body. In an experimental canine model the pharmacokinetics of i.a. infusion were studied using the femoral artery as the site of infusion and an Anger camera for continuous measurement of drug concentration in the target region. Several radioactively labelled drugs with different kinetics were infused over 80 min. The decay phase after the end of i.a. infusion was also monitored. The results indicate that even the femoral artery with its high blood flow is a suitable site for i.a. infusion, provided the plasma half-life of the drug is short enough. Consequently, arteries with lower blood flow (e.g., lingual artery) are even more suitable for i.a. infusion. The various diagrams obtained from this study provide a quick indication of whether or not a drug is suitable in a certain clinical situation.

[Emission computed tomography of the left ventricle. Multiplanar ECG-triggered radionuclide ventriculography with a 7-pinhole collimator]. / Emissionscomputertomographie des linken Ventrikels. Multiplanare EKG-getriggerte Radionuklidventrikulographie mit dem 7-pinhole-Kollimator.

Tomographic studies and time-dependent tomograms on phantoms and patients were carried out using a 7-pinhole collimator in order to study the clinical value of ECG-triggered tomographic radionuclid ventriculography. A suitable computer programme has been developed. The results have shown that it is possible to evaluate local contraction abnormalities by this method. Using a left oblique position of the collimator (LAO [45 degrees]-cranial [15 degrees] ), emission computer tomography is aligned with the longitudinal axis of the heart. In this way, a single projection is sufficient to show the motility of the anterior and posterior walls and of the septum. Hypokinesis, akinesis or dyskinesis can be recognised visually. The localisation and extent of the defect can be determined through the 7-pinhole collimator. Reconstructed images of the triggered radionuclid scintigrams show excellent marginal definition. In the RAO projection, the left ventricle can be seen without superimposition and images obtained which equal those of a first-pass technique.

[Estimation of 131I-Iodohippurate-clearance by a simplified method using a single plasma sample (author's transl)]. / Die Bestimmung der 131J-Hippuranclearance nach einer vereinfachten Methode mit nur einer Blutentnahme.

Theoretical volumes calculated from the reciprocal of the plasma concentration after intravenous injection of 131I-Iodohippurate were compared in 95 patients with clearance values calculated by the 2-compartment-method and in 18 patients with conventional PAH-clearance. For estimating Hippurate-clearance from a single blood sampling the most favorable time is 45 min. after injection (r = 0.96; clearance < 400/ml/min.: r = 0.98). Clearance values may be derived from the formula: C = 0.4 + 7.26 V - 0.021 . V2 (V = injected activity/activity per l plasma taken 45 min. after injection). The simplicity, precision and reproducibility of the above mentioned clearance-method is emphazised.

[Bone density measurements by computer tomography (author's transl)]. / Knochendichtemessung mit dem Computertomographen.

The suitability of the E.M.I. mark I computer scanner for carrying out bone densitometry has been tested, using the forearm. Within the region of interest there was an almost linear relationship between CT densities and the concentration of the bone equivalent substance K2HPO4. By means of a special computer programme, the spongiosa and cortex of both forearm bones could be analysed quantitatively. The reproducibility of the results (coefficient of variation 5%) was similar to that of other procedures in current use. The advantage of the method lies in the fact that it is possible to estimate the spongiosa and cortex separately. Investigations on patients with normal bones have shown that senile demineralisation affects the cortex most severely. On the other hand, in renal osteopathies of chronically dialysed patients, demineralisation in the forearm predominantly involves the spongiosa.