Percutaneous renal intervention: comparison of 2-D and time-resolved 3-D (4-D) ultrasound for minimal calyceal dilation using an ultrasound phantom and fluoroscopic control

The rapid advances made by ultrasound in recent years have increasingly taken 3-D ultrasound (3DUS) and 4-D ultrasound (4DUS) from the research setting to the patient's bedside. There are still unexplored areas like renal percutaneous intervention, where 4DUS has yet to be proven an effective tool. Ultrasound-only guidance in renal percutaneous access is used in selected well-dilated pelvi-calyceal systems (PCS), and fluoroscopy is often utilized as an adjunct. Our aim was to compare 2-D and 4-D guidance for punctures, with fluoroscopy as control, using an in vitro ultrasound phantom. Agar and latex were the tissue-mimicking materials used for the construction of the phantom. The latex targets were designed to simulate multidirection-facing minimally dilated renal calyces. Two interventional fellows punctured the "calyces" using first 2DUS and then 4DUS guidance, making use of a different set of targets each time. The time to puncture, time to introduction of wire, quality of puncture (judged on fluoroscopy) and global rating of both modalities were documented. There was no significant difference between the times to puncture using 2DUS (1.8 min) and 4DUS (2 min). Nor was there a significant difference in the quality of puncture. 4DUS had a higher median difficulty rating. The multiplanar reformatted (MPR) longitudinal and transverse images were found to be the most useful for needle guidance. Cross hairs in all MPR images were not just useful in aligning the images on target but also as surrogate targets. The phantom was found to be robust, with only one instance of air introduction after 30 punctures. We have found that 4DUS is at least as good as 2DUS in terms of quality of punctures in vitro. The technology still has some way to go as frame rates, transducer size and resolution improve.     

Non-human pancreas as substrate for cytoplasmic islet cell antibodies

To investigate qualitative and quantitative differences in islet cell antibody (ICA) detection within and between species we evaluated 8 pancreatic substrates (2 human, 2 baboon, 2 macaque, 1 pig and 1 rat). All substrates were able to detect strongly positive sera (with ICA greater than 160 JDF units). Non-human primate pancreata showed a larger size and greater abundance of islets than human, pig or rat. Significant differences in end point titter were observed both within and between species. In comparing the two best pancreata (1 human and 1 macaque) in masked screening of 50 normal controls and 108 nondiabetic first degree relatives of type 1 diabetics, very similar results were obtained. We concluded that pancreatic substrates from a variety of species may be useful for detection of ICA. This study, however, underscores the need for between and within assay standardization of ICA such as those currently underway in the International Immunology of Diabetes Workshops and Proficiency Tests.     

Evaluation of Bremsstrahlung radiation dose in stereotactically radiocolloid therapy of cystic craniopharyngioma tumors with <Superscript>32</Superscript>P radio-colloid

Over 90% of craniopharyngeal brain tumors are cystic, which enables the injection of beta emitters such as phosphorus-32 (³²P) radio-colloid into cysts for their treatment. The aim of this study was to evaluate the clinical and theoretical modelling of Bremsstrahlung radiation dose resulting from stereotactic radio-colloid therapy of cystic craniopharyngioma tumors with ³²P. ³²P radio-colloid with appropriate activity concentration was injected to a head phantom, and then the Bremsstrahlung radiation spectrum and planar images were obtained using a gamma camera. Both phantom and gamma camera were simulated using MCNPX code, and the results were compared with practical results. Bremsstrahlung radiation spectrum was measured using a handheld gamma spectrometer for two patients treated with stereotactic radio-colloid therapy with ³²P in different positions and compared to Monte Carlo simulation. Results of counting and determining sensitivity coefficients in the air and the attenuating environment were obtained. Also, comparing the counting sensitivity from practical and simulation methods indicated the agreement of the data between the two methods. Comparison of the spectra from different positions around patient’s head indicated the ability to use this detector to quantify the activity in the operating room. Selection of the spectrum is important in Bremsstrahlung radiation imaging. We can take advantage of spectrometry measurement using gamma camera, handheld gamma spectrometer for patient, and theoretical modeling with Monte Carlo code to evaluate radiopharmaceutical distribution, leakage, as well as estimate activity and predict therapeutic effects in other adjacent structures and ultimately optimize radio-colloid therapy in cystic craniopharyngeal patients.     

Perihematoma cerebral blood flow is unaffected by statin use in acute intracerebral hemorrhage patients

Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting <24 hours from ICH onset were randomized to a systolic blood pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume.     

Recognition and sequestration of ω-fatty acids by a cavitand receptor

One of the largest driving forces for molecular association in aqueous solution is the hydrophobic effect, and many synthetic receptors with hydrophobic interiors have been devised for molecular recognition studies in water. Attempts to create the longer, narrower cavities appropriate for long-chain fatty acids have been thwarted by solvophobic collapse of the synthetic receptors, giving structures that have no internal spaces. The collapse generally involves the stacking of aromatic panels onto themselves. We describe here the synthesis and application of a deep cavitand receptor featuring “prestacked” aromatic panels at the upper rim of the binding pocket. The cavitand remains open and readily sequesters biologically relevant long-chain molecules—unsaturated ω-3, -6, and -9 fatty acids and derivatives such as anandamide—from aqueous media. The cavitand exists in isomeric forms with different stacking geometries and n-alkanes were used to characterize the binding modes and conformational properties. Long alkyl chains are accommodated in inverted J-shaped conformations. An analogous cavitand with electron-rich aromatic walls was prepared and comparative binding experiments indicated the role of intramolecular stacking in the binding properties of these deep container molecules.Molecular recognition of long-chain fatty acids, lipids, membrane components, and hydrocarbons in water poses the general problems of size, shape, and surface complementarity and the special problem of solubility. What types of structures offer large lipophilic surfaces but still dissolve in water? Natural receptors such as the fatty acid-binding proteins (FABPs) incorporate hydrophobic cavities within superstructures with hydrophilic surfaces. The protein backbone and dense packing of side chains prevent collapse of the cavities. Synthetic receptors of the appropriate recognition features comprise deep cavitands (1) and other open-ended host structures (2, 3) that more or less fold around their guest targets. As initially encountered by Cram et al. (4), deep cavitands are dynamic and interconvert between two conformations in organic media: a receptive “vase” form and the unreceptive “kite” form as its dimeric “velcrand” (Fig. 1) (4–8). Stacking of aromatic surfaces in the velcrand buries one face of each kite and is driven by a generalized solvophobic effect. The vase can be rigidified by covalent bonds (9–13) but in water the dynamic cavitands collapse into velcrands through the more specific hydrophobic effect. The presence of appropriate guests shifts the equilibrium to the vase conformation: The guest must fit into, fill, and solvate the cavitand host’s hydrophobic interior. Binding of guest molecules by container compounds is often dependent on the volume of the host. Recognition of long-chain, linear hydrocarbons by biological receptors and synthetic supramolecular hosts generally involves ∼55% volume occupancy and relatively low surface complementarity (14–16). Cavitands with a depth of 1 nm are readily prepared and bind medium-chain n-alkanes, from octane (C₈) to decane (C₁₀). Longer alkanes such as tetradecane (C₁₄) often induce the formation of dimeric, capsule-like assemblies in which the alkyls assume compressed conformations involving folding and coiling (17, 18). Common, long-chain fatty acids bearing saturated or unsaturated alkyl chains are not readily accommodated in dimeric capsules (19, 20) or in the vase forms of typical cavitands. Here, we report a deeper cavitand with a longer, narrower cavity that readily sequesters physiologically relevant fatty acids and derivatives from aqueous media.Open in a separate windowFig. 1.Modeled depictions of cavitand conformations. Cavitands interconvert between a vase shape (Left) and a flattened kite shape (Center). The kite can dimerize to a velcrand (Right) through solvophobic interactions, whereas the vase is favored by the presence of guests that can solvate the cavity.