Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of^99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of^99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. This phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion,^99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.     

Changes in AMPA receptor currents following LTP induction on rat CA1 pyramidal neurones

In the CA1 region of the hippocampus, LTP is thought to be initiated by a transient activation of NMDA receptors and is expressed as a persistent increase in synaptic transmission through AMPA receptors. To investigate the postsynaptic modifications of AMPA receptors involved in this enhanced synaptic transmission, the channel density and single-channel properties of extrasynaptic AMPA receptors located in synaptically active dendritic regions were examined following the induction of LTP. Following tetanic stimulation an outside-out patch was excised from the apical dendrite near the point of stimulation and saturating concentrations of glutamate were rapidly applied to the patch. AMPA current amplitude and duration were increased significantly in patches pulled from dendrites that expressed LTP. Non-stationary fluctuation analysis of AMPA currents indicated that AMPA channel number was nearly twofold larger than in controls, while single channel conductance and maximum open-probability were unchanged. Furthermore, while subtle changes in AMPA channel kinetics could also be observed, we did not find any evidence that receptor affinity or rectification properties were altered by LTP induction. Very similar results were found when CaMK-II activity was increased through the intracellular application of Ca/CaM. Together, we interpret our data to indicate that the stimuli used here produce an increased delivery of AMPA receptors to synaptically active regions of the apical dendrite without inducing any significant changes in their basic biophysical properties and that such delivery is a key element in this form of synaptic plasticity.     

Effect of peripheral axotomy on the fine structure and histochemistry of the Rolando substance: Degenerative atrophy of central processes of pseudounipolar cells

Summary Disappearence of fluorid-resistant acid phosphatase activity from the ipsilateral Rolando substance after transection of the peripheral nerve, is shown to be due to the cessation of enzyme supply from dorsal root ganglion cells to their central terminals. This is accompanied by (or ensues in consequence of) a fine structural derangement of these terminals (degenerative atrophy). Fine structural alterations of axon terminals undergoing degenerative atrophy, though similar to some extent to those seen during early phases of a Wallerian degeneration, are markedly different. Also myelinated nerve fibers, both in the dorsal horn and in dorsal columns, are affected by degenerative atrophy. This important, new trophical feature of sensory ganglion cells suggests a delicate metabolic balance between peripheral and central axonal branches of bipolar (pseudounipolar) cells. Degenerative atrophy raises serious implications in evaluating hodological experiments based upon Wallerian degeneration and offers new perspectives for theoretical and clinical neurology.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Investigation of the polymerization of octanelactam initiated with hydrochloric acid

The polymerization of octanelactame ( 1 ) initiated by HCl takes place according to the characteristic kinetic curves. Both characteristics, i.e., the fast initial and the extremely slow further stages, and the kinetic anomaly (in certain cases under otherwise identical conditions less polymer is formed at higher than at lower temperatures) can be interpreted easily on the basis of a mechanism already suggested by the authors. The two relevant chain growth reactions, i.e., lactam addition on \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm R}\mathop {\rm N}\limits^ \oplus {\rm H}_{\rm 3} $\end{document}-groups and the reaction between \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm R}\mathop {\rm N}\limits^ \oplus {\rm H}_{\rm 3} $\end{document} and N-acylamide groups, proceed through a tetrahedral intermediate in two directions, one of them being the known chain growth, the other one an amidine (or acylamidine) formation, in which the active groups, ensuring chain growth, desactivate. Both kinetic characteristics could be interpreted on the basis of the suggested mechanism, by measuring the amounts of amino and amidine groups with the progress of polymerization.     

Primary afferent origin of substance P-containing axons in the superficial dorsal horn of the rat spinal cord: depletion, regeneration and replenishment of presumed nociceptive central terminals

Substance P-like immunoreactivity (SPLI) was localized in the superficial spinal dorsal horn of the rat by means of light and electron microscopic immunocytochemical techniques. Serial immunocytochemical sections were subjected to densitometric measurements with an electronic Image Analyser, and with aid of a computer program, a two-dimensional reconstruction of the fine neuroanatomical structure of the SPLI-active regions of the lumbosacral upper superficial spinal dorsal horn was obtained. SPLI activity in the superficial dorsal horn outlines four well-marked and distinctly differing regions, called, in the mediolateral sequence, areas A, B, C, and D, plus Cajal's noyeau interstitiel ("lateral spinal nucleus" = "nucleus of the dorsolateral fascicle," L). Lumbosacral dorsal rhizotomy results in an almost complete depletion of SPLI from ipsilateral areas A, B, C, and D; it induces decreased SPLI in the area of the lateral spinal nucleus (L), ipsi- or contralaterally in an alternating fashion. Transection of the segmentally related, ipsilateral peripheral nerve induces a marked depletion of SPLI from areas A, B, and C but only a slight decrease in area D and virtually none in the area of L. Whereas a simple crush of the peripheral nerve (axocompression) induces only a slight depletion of SPLI, if any, semiautomatic densitometric analysis of serial immunocytochemical sections proves that a controlled crush injury (axocontusion) results in depletion of SPLI from the upper dorsal horn, similar to transection of the peripheral nerve. Following regeneration of the ipsilateral, segmentally related peripheral nerve, the original immunocytochemical structure of the superficial dorsal horn is re-established by SPLI-positive axonal sprouts originating from previously damaged dorsal root axons.     

Local conformal autoencoder for standardized data coordinates

We propose a local conformal autoencoder (LOCA) for standardized data coordinates. LOCA is a deep learning-based method for obtaining standardized data coordinates from scientific measurements. Data observations are modeled as samples from an unknown, nonlinear deformation of an underlying Riemannian manifold, which is parametrized by a few normalized, latent variables. We assume a repeated measurement sampling strategy, common in scientific measurements, and present a method for learning an embedding in Rd that is isometric to the latent variables of the manifold. The coordinates recovered by our method are invariant to diffeomorphisms of the manifold, making it possible to match between different instrumental observations of the same phenomenon. Our embedding is obtained using LOCA, which is an algorithm that learns to rectify deformations by using a local z-scoring procedure, while preserving relevant geometric information. We demonstrate the isometric embedding properties of LOCA in various model settings and observe that it exhibits promising interpolation and extrapolation capabilities, superior to the current state of the art. Finally, we demonstrate LOCA’s efficacy in single-site Wi-Fi localization data and for the reconstruction of three-dimensional curved surfaces from two-dimensional projections.     

Effect of nalbuphine on the motility of the sphincter of Oddi in patients with suspected sphincter of Oddi dysfunction

BACKGROUND: Nalbuphine is an ideal supplementary analgesic drug for midazolam-induced conscious sedation during operative endoscopy because it has no cardiovascular effect and only a moderate depressive effect on respiration. However, no data are available as to whether nalbuphine is suitable as an analgesic drug during endoscopic sphincter of Oddi manometry. The aim of the present study was to investigate the effect of nalbuphine on the sphincter of Oddi motility in patients with a suspected sphincter of Oddi dysfunction. METHODS: Seventeen patients who were suspected clinically to have SOD after cholecystectomy were prospectively investigated. Five mg of midazolam was administered intravenously before the procedure to induce conscious sedation. After approximately 5 minutes of stationary sphincter of Oddi manometry recording (baseline), either 10 mg of nalbuphine or saline solution (placebo) was administered intravenously in random fashion and pressure was recorded for a further 5 minutes. Maximum sphincter of Oddi basal pressure and average phasic contraction amplitude and frequency were measured before and after the infusion of the drug or saline solution. RESULTS: Nalbuphine administration effectively enhanced the sedation obtained with midazolam without any adverse effect. When the sphincter of Oddi manometric periods before and after the administration of nalbuphine versus placebo were compared, there was a significantly increased basal sphincter of Oddi pressure only in the nalbuphine group: respectively, 49 (18) and 77 (29) mm Hg (p = 0.003) versus 51 (24) and 49 (23) mm Hg (p = 0.9). The phasic contraction amplitude did not change in response to nalbuphine, but the phasic contraction frequency increased significantly, from 5 (3) to 8 (4) per minute (p = 0.04). CONCLUSIONS: Nalbuphine has a stimulatory effect on sphincter of Oddi motility in patients with a suspected sphincter of Oddi dysfunction. Nalbuphine should not be used as premedication before endoscopic ERCP if sphincter of Oddi manometry is to be performed.