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Results for “Collateral sensitivity”

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PubMed1999

Differential sensitivities of the two visual pathways of the chick to labelling by fluorescent retrograde tracers.

This study investigates the neurone structure-specific differences of sensitivities of fluorescent tracers. The tracers were used for retrograde labelling of contralateral projections in the two visual pathways of the chick. Rhodamine B Isothiocyanate (RITC), Fluorogold (FG) and True blue (TB) were injected into either the visual Wulst (thalamofugal pathway) or the nucleus rotundus (Rt; tectofugal pathway) and the retrogradely labelled neurones in the nucleus geniculatus lateralis pars dorsalis (GLd) or the optic tectum, respectively, were counted. Differential retrograde labelling in the two pathways was observed. In the thalamofugal pathway, both the contralateral and ipsilateral GLd cells were labelled by all three tracers (RITC, FG and TB). However, in the tectofugal pathway, whereas RITC labelled both the ipsilateral and contralateral tectal neurones, FG or TB labelled effectively only the ipsilateral tectal neurones. It was clear that FG and TB were taken up by the nerve endings and transported part-way along the axon but failed to be transported to the cell bodies of the contralateral tectal neurones. In addition, red beads and green beads were also injected into Rt and the differential labelling was also observed. Red beads labelled both ipsilateral and contralateral tectal neurones but green beads labelled only the ipsilateral tectal neurones. Since the contralateral tectal projections consist of divergent axon collaterals, the present study suggests that various retrograde tracers are not transported in these axon collaterals to label cell bodies. The contralaterally projecting neurones in the thalamofugal pathway are not axon collaterals and they were labelled by all of the tracers used.

Animals↗

PubMed2005

Assessing alexithymia and related emotional ability constructs using multiple methods: interrelationships among measures.

This study examined relationships among various measures of emotional ability reflecting different methods of assessment: self-report, clinical interview, collateral report, and emotion-relevant performance. On 140 young adults, the authors assessed self-reported alexithymia, emotional approach coping, and trait metamood skills; observer-reported alexithymia; interviewer-rated alexithymia; emotional awareness in response to vignettes; and emotional intelligence test performance. There were moderate magnitude correlations among the self-report measures, but correlations among other measures were relatively low. Confirmatory factor analyses supported a 3-factor model in which explicit self, implicit self, and explicit other measures were differentiated. These emotional ability measures do not form a unitary construct but differ as a function of the person providing the information and whether the measure is explicit or implicit.

Adolescent↗

PubMed2002

Ifenprodil and ethanol enhance NMDA receptor-dependent long-term depression.

Long-term alterations in synaptic transmission are thought to underlie various types of alcohol-related brain disorders. While ethanol effects on synaptic potentiation are well documented, ethanol effects on synaptic depression have not been addressed. Herein, we performed experiments to assess the role of ethanol on long-term depression (LTD) formation. In rat hippocampal slices, prolonged low-frequency stimulation (LFS) of CA1 Schaffer collaterals (1 Hz for 7 min) induced saturable, long-lasting, reversible N-methyl-D-aspartate (NMDA) receptor-dependent LTD of stimulus-evoked dendritic population excitatory postsynaptic potentials. This depression (-26% LTD amplitude) was observed in young rats (12-20 days old), but not adult rats (28-35 days old). Induction of LTD was blocked (-3% LTD amplitude) when the LFS was delivered in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid. When the conditioning LFS was delivered in the presence of ethanol, there was a significant enhancement in the induction of NMDA receptor-dependent LTD versus control LTD (-36% LTD amplitude). Ifenprodil, an N-methyl-D-aspartate receptor subunit 2B (NR2B)-selective antagonist, also significantly facilitated the induction of LTD (-40% LTD amplitude). Consistent with this result, ifenprodil did not affect the NMDA receptor-dependent component of the baseline synaptic response, whereas D-2-amino-5-phosphonovaleric acid caused significant depression of the NMDA component. These data indicate that whereas ethanol is known to inhibit NMDA receptor function in a variety of systems, it significantly enhances the induction of NMDA receptor-dependent LTD. Furthermore, since ifenprodil is known to select for ethanol-sensitive subtypes of NR2B-NMDA receptors, these data also suggest that NR2B-containing NMDA receptor subpopulations do not contribute to LTD, but instead may actually play inhibitory roles in LTD induction.

Animals↗

PubMedDate not supplied

Prospective evaluation of two diagnostic apprehension signs for posterolateral instability of the elbow.

Posterolateral rotatory instability (PLRI) of the elbow occurs from attrition of the lateral ulnohumeral collateral ligament of the elbow after elbow dislocation. Diagnosis by physical examination can be difficult in the awake patient. The goals of this study were to define two active apprehension signs for the physical diagnosis of PLRI and to perform a prospective evaluation of the signs in a series of patients with PLRI. Eight patients with PLRI undergoing surgical reconstruction of the lateral ulnocollateral ligament of the elbow were prospectively included in this continuous case series. Preoperative evaluation consisted of physical examination with two active apprehension signs, the chair sign and the pushup sign, as well as the pivot-shift sign. Results were compared with repeat physical examination after reconstruction of the ligaments. Of 8 patients included in the series, 3 demonstrated a positive pivot-shift sign while awake, and all demonstrated a positive pivot-shift sign while under anesthesia. Seven patients demonstrated a positive chair sign, and seven demonstrated a positive pushup sign. At the 2-year follow-up evaluation, 7 patients remained stable and asymptomatic. The pushup sign, chair sign, and pivot-shift sign were negative in all 7 patients. The study demonstrated that both the pushup and chair signs are effective in aiding the diagnosis of PLRI. They are more sensitive than the pivot-shift sign in the awake patient and may be easily performed in the office environment.

Adult↗

PubMed1994

An absent ophthalmic artery or carotid siphon signal on transcranial Doppler confirms the presence of severe ipsilateral internal carotid artery disease.

Transcranial Doppler ultrasound provides a useful adjunct to extracranial ultrasound in the diagnosis of carotid bifurcation disease. Previous studies have shown that collateral flow patterns and diminished flow velocities in the ipsilateral middle cerebral artery correlate with hemodynamically significant carotid disease. In a series of 7,054 carotid duplex and transcranial Doppler examinations, 12.5% (95% confidence interval [CI]: 8.7, 16.4) of 287 ophthalmic arteries ipsilateral to an apparent carotid occlusion had no detectable flow signal, compared with 0.5% (95% CI: 0.3, 0.7) of 6,767 ophthalmic arteries ipsilateral to a non-occluded carotid artery (p < 0.001). Carotid siphon signals were not detectable in 24.4% (95% CI: 19.4, 29.4) of arteries ipsilateral to the carotid occlusion, versus 1.0% (95% CI: 0.8, 1.3) ipsilateral to nonoccluded carotid arteries (p < 0.001). A significant number of absent ophthalmic artery and carotid siphon signals (5.7 and 8.7%, respectively) were also found in patients with 80 to 99% extracranial carotid stenosis. A subset of 216 studies with angiographic correlation confirmed the high association of these transcranial Doppler findings with severe stenosis or occlusion of the internal carotid artery. Primary ophthalmological disease or siphon occlusion did not explain these findings. An absent ophthalmic artery or carotid siphon signal on transcranial Doppler examination is believed to represent a failure to detect slow flow distal to severe carotid bifurcation lesions. As a sign of ipsilateral carotid occlusion, the sensitivities of absent ophthalmic artery and carotid siphon signals are quite low (12.5 and 24.4%, respectively). The high specificities of 99.5 and 99.0%, however, make these findings useful in confirming the diagnosis of presumptive carotid occlusion by carotid duplex ultrasound.

Blood Flow Velocity↗

PubMed1991

Asymptomatic myocardial ischemia during percutaneous transluminal coronary angioplasty and importance of prior Q-wave infarction and diabetes mellitus.

Eighty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) of 100 stenoses were studied for the presence of factors deemed significant in the etiology of silent myocardial ischemia. Thirty-two patients were asymptomatic during balloon dilations of 36 arteries, and 56 patients had angina during PTCA of 64 arteries. There were no differences in age, sex, prior anginal history, antianginal regimen, extent of coronary artery disease and number or duration of inflations between the 2 study groups. Previous infarction (33 vs 12%, p less than 0.02), Q waves in the target area (31 vs 7%, p less than 0.005) and diabetes mellitus (36 vs 17%, p less than 0.05) were present more often in the asymptomatic group. Sixty-four% of all asymptomatic patients had either diabetes or previous infarction in the target territory. Collateral circulation was more frequent in asymptomatic patients, probably reflecting the ability of collateral arteries to ameliorate ischemia. During 2-vessel PTCA, patients without angina during dilation of only 1 of the 2 treated arteries (discordant responders) had previous infarction in that artery's territory (5 of 5, 100%), whereas patients without previous infarction were either symptomatic or asymptomatic (concordant responders) during PTCA of both arteries. This study shows that asymptomatic ischemia occurs frequently during PTCA in patients with symptomatic coronary disease. Prior Q-wave infarction and diabetes mellitus are important, independent factors associated with painless ischemia. It is suggested that infarction produces a localized dysfunction of afferent cardiac pain fibers, whereas diabetes can cause a global cardiac sensory neuropathy.

Aged↗

PubMed1994

Transcranial Doppler correlation with angiography in detection of intracranial stenosis.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the use of velocity criteria applied to transcranial Doppler (TCD) signals in the detection of stenosis of the middle cerebral (MCA), distal vertebral, and basilar arteries. METHODS: Sixty-five patients who underwent both cerebral angiography and transcranial Doppler examinations in the workup of acute cerebral ischemia were reviewed. Angiography was performed a mean of 7 +/- 5 days (range, 1 to 28 days) after TCD. Interpretation of the angiogram was performed without input regarding the TCD findings. TCD interpretation was performed according to standard criteria. RESULTS: When we used a mean velocity (MV) cutoff of > or = 80 cm/s in the MCA as the criterion for stenosis, 10 of 12 stenoses of any degree were detected by TCD, with 11 of 87 false-positives. Nine of 12 MCA stem (M1) stenoses were detected when a cutoff of > or = 90 cm/s was used, with 7 of 87 false-positives. When we used an MV cutoff of > or = 70 cm/s as the criterion for > or = 50% stenosis of the vertebrobasilar system, 5 of 6 stenoses were detected, with 15 of 85 false-positives. The most important confounding factor was the presence of > or = 75% stenosis of the extracranial internal carotid artery, resulting in both false-positive (from collateral flow) and false-negative (decreased volume flow from the proximal stenosis without adequate collateral flow) errors in TCD interpretation. When patients with > or = 75% stenosis of the cervical internal carotid artery were excluded from analysis, a TCD MV cutoff of > or = 80 cm/s identified 9 of 10 M1 lesions with 7 of 61 false-positives, and an MV of > or = 70 cm/s identified 3 of 4 vertebrobasilar lesions causing > or = 50% stenosis with 7 of 56 false-positives. CONCLUSIONS: TCD may be an effective screening test for M1 stenosis when velocity criteria alone are used. TCD may less reliably detect intracranial vertebral and basilar artery stenosis.

Adult↗

PubMed2005

Multi-detector computed tomography angiography of the hepatic artery in liver transplant recipients.

PURPOSE: To evaluate the ability of multi-detector row computed tomography angiography (CTA) in detecting hepatic artery complications in the follow-up of liver transplant patients, performing volume-rendering as reconstruction technique. MATERIAL AND METHODS: The anatomy of hepatic artery was studied in 27 liver transplant recipients with a four-row CT scanner using the following parameters: collimation, 1 mm; slice width, 1 mm; table feed, 6-8 mm/s; spiral reconstruction time, 0.5 s; reconstruction interval, 0.5 mm; mAs, 160; kVp, 120. Before the study, the patients received 1000 ml of water as oral contrast agent to produce negative contrast in the stomach and the small bowel. A non-ionic contrast medium was infused intravenously at a rate of 5 ml/s with a bolus tracking system. Volume-rendering of hepatic artery was performed with the 3D Virtuoso software. RESULTS: The celiac trunk, the hepatic artery, and the right and left hepatic arteries were successfully displayed in high detail in all patients. Side branches, including small collaterals, and hepatic artery anastomosis could also be readily visualized. Volume-rendered CTA detected six hepatic artery stenoses, two hepatic artery thromboses, and two intrahepatic pseudoaneurysms. In two cases, CT detected hepatic artery stenosis with a diameter reduction of less than 50%, while digital subtraction angiography showed a normal artery. CONCLUSION: Volume-rendered multi-detector CTA is a promising non-invasive technique, since it allows images of high quality to be generated with excellent anatomical visualization of the hepatic artery and its complications in liver transplant recipients.

Adult↗

PubMed1989

Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: response to fimbria-fornix transection.

Although it is well known that magnocellular cholinergic basal forebrain neurons are trophically responsive to nerve growth factor (NGF) and contain NGF receptors (NGFr), the exact distribution of forebrain NGFr-immunoreactive neurons and the degree to which cholinergic neurons are colocalized with them have remained in question. In this study we employed a very sensitive double-labelling method and examined in the same tissue section the distribution and cellular features of NGFr-positive and choline acetyltransferase (ChAT)-immunolabelled neurons within the rat basal forebrain. Throughout this region the majority of magnocellular basal forebrain neurons were immunoreactive for both NGFr and ChAT. However, a small percentage of neurons in the ventral portion of the vertical limb of the diagonal band of Broca were immunoreactive only for NGFr, whereas a larger population of magnocellular neurons in the substantia innominata exhibited only ChAT immunoreactivity. No NGFr-immunoreactive cells were found associated with ChAT-positive neurons in the striatum, neocortex, or hippocampus, and no single-labelled NGFr-immunoreactive neurons were found outside the basal forebrain area, except for a large number of positive-labelled cells along the ventricular walls of the third ventricle. In addition to its function in maintaining the normal integrity of the basal forebrain and cholinergic, peripheral sympathetic, and neural-crest-derived sensory neurons, NGF may also have a role in the growth of these neurons after damage to the nervous system. To examine this postulate the hippocampus was denervated of its septal input and examined 8 weeks later. Two populations of neurons were found to have undergone collateral sprouting--namely, the midline magnocellular cholinergic neurons of the dorsal hippocampus and the sympathetic noradrenergic neurons of the superior cervical ganglion. Both of these neuronal populations also stained strongly for NGFr. In contrast, the small intrinsic cholinergic neurons of the hippocampus exhibited neither sprouting response nor staining for NGFr. In view of these results, we suggest that the differing sprouting responses demonstrated by these three neuronal populations may be due to their responsiveness to NGF, as indicated by the presence or absence of NGF receptors.

Animals↗

PubMed2000

Color Doppler sonography in the diagnosis and monitoring of arterial complications after liver transplantation.

PURPOSE: We assessed the usefulness of color Doppler imaging in the diagnosis and monitoring of arterial complications after liver transplantation. METHODS: Subjects were 142 liver transplant recipients who underwent serial color Doppler sonographic evaluations of the hepatic arteries after surgery. Patients with abnormal sonographic findings underwent subsequent angiography. RESULTS: Eighteen subjects experienced 20 hepatic arterial complications (13 thromboses and 7 stenoses). In 7 of the 13 thrombosis incidents, hepatic arterial obstruction occurred within a month of surgery and was evident from the absence of Doppler signals; angiography confirmed the absence of hepatic arterial perfusion in these cases. In the other 6 thrombosis cases, the thrombosis developed 3 or more months after surgery and became apparent from the absence of color Doppler signals at the level of the main arterial trunk and the presence of intraparenchymal "tardus parvus" waveforms. In these cases, angiography showed obstruction of the main arterial trunk and the development of compensatory collateral vessels. In 3 of the 7 cases of stenosis, high flow velocities were recorded at the site of the narrowing, and intrahepatic tardus parvus waveforms were present. In the other 4 stenosis cases, the site of stenosis could not be identified, but intraparenchymal tardus parvus waveforms were recorded. CONCLUSION: The use of color Doppler sonography allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus parvus waveforms indicated severe impairment of hepatic arterial perfusion, from either thrombosis or severe stenosis. The presence of these waveforms enhanced the accuracy of color Doppler diagnosis (100% positive predictive value), and their detection should prompt angiography.

Adult↗

PubMed2001

Experimental localization of Kv1 family voltage-gated K+ channel alpha and beta subunits in rat hippocampal formation.

In the mammalian hippocampal formation, dendrotoxin-sensitive voltage-gated K(+) (Kv) channels modulate action potential propagation and neurotransmitter release. To explore the neuroanatomical basis for this modulation, we used in situ hybridization, coimmunoprecipitation, and immunohistochemistry to determine the subcellular localization of the Kv channel subunits Kv1.1, Kv1.2, Kv1.4, and Kvbeta2 within the adult rat hippocampus. Although mRNAs encoding all four of these Kv channel subunits are expressed in the cells of origin of each major hippocampal afferent and intrinsic pathway, immunohistochemical staining suggests that the encoded subunits are associated with the axons and terminal fields of these cells. Using an excitotoxin lesion strategy, we explored the subcellular localization of these subunits in detail. We found that ibotenic acid lesions of the entorhinal cortex eliminated Kv1.1 and Kv1.4 immunoreactivity and dramatically reduced Kv1.2 and Kvbeta2 immunoreactivity in the middle third of the dentate molecular layer, indicating that these subunits are located on axons and terminals of entorhinal afferents. Similarly, ibotenic acid lesions of the dentate gyrus eliminated Kv1.1 and Kv1.4 immunoreactivity in the stratum lucidum of CA3, indicating that these subunits are located on mossy fiber axons. Kainic acid lesions of CA3 dramatically reduced Kv1.1 immunoreactivity in the stratum radiatum of CA1-CA3, indicating that Kv1.1 immunoreactivity in these subfields is associated with the axons and terminals of the Schaffer collaterals. Together with the results of coimmunoprecipitation analyses, these data suggest that action potential propagation and glutamate release at excitatory hippocampal synapses are directly modulated by Kv1 channel complexes predominantly localized on axons and nerve terminals.

Animals↗

PubMed1992

Multiple metabotropic glutamate receptors regulate hippocampal function.

Selective activation of metabotropic glutamate receptors with trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) stimulates phosphoinositide hydrolysis and elicits three major physiological responses in area CA1 of the hippocampus. These include direct excitation of pyramidal cells, blockade of synaptic inhibition, and decreased transmission at the Schaffer collateral-CA1 pyramidal cell synapse. Physiological effects of trans-ACPD are thought to be mediated by activation of phosphoinositide hydrolysis. However, it is now clear that multiple metabotropic glutamate receptor subtypes exist, some of which are not coupled to phosphoinositide hydrolysis. Thus, we performed a series of studies aimed at determining whether the physiological effects of trans-ACPD in the hippocampus are mediated by activation of the predominant phosphoinositide hydrolysis-linked glutamate-receptor. We report that L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist of trans-ACPD-stimulated phosphoinositide hydrolysis, does not inhibit the physiological effects of trans-ACPD in area CA1 at concentrations that maximally inhibit trans-ACPD-stimulated phosphoinositide hydrolysis in this region. Furthermore, 1S,3S-ACPD activates the phosphoinositide hydrolysis-linked glutamate receptor but does not reduce evoked field excitatory postsynaptic potentials (EPSPs) in area CA1. However, we report that the physiological effects of 1R,3S- and 1S,3R-ACPD are consistent with the hypothesis that these effects are mediated by activation of a metabotropic glutamate receptor. Thus, our data are consistent with the hypothesis that the physiological effects of trans-ACPD in area CA1 of the hippocampus are mediated by metabotropic glutamate receptors that are distinct from the AP3-sensitive phosphoinositide hydrolysis-linked glutamate receptor.

Alanine↗

PubMed2000

Cerebellar on-beam and lateral inhibition: two functionally distinct circuits.

Optical imaging of voltage-sensitive dyes in an isolated cerebellum preparation was used to study the spatiotemporal functional organization of the inhibitory systems in the cerebellar cortex. Responses to surface stimulation of the cortex reveal two physiologically distinct inhibitory systems, which we refer to as lateral and on-beam inhibition following classical terminology. Lateral inhibition occurs throughout the area responding to a stimulus, whereas on-beam inhibition is confined to the area directly excited by parallel fibers. The time course of the lateral inhibition is twice as long as that of the on-beam inhibition. Both inhibitory responses increase with stimulus intensity, but the lateral inhibition has a lower threshold, and it saturates at lower stimulus intensity. The amplitude of the on-beam inhibition is linearly related to the excitation at the same location, whereas that of the lateral inhibition is linearly related to the excitation at the center of the beam. Repetitive stimulation is required to activate on-beam inhibition, whereas the same stimulus paradigm reveals prolonged depression of the lateral inhibition. We conclude that lateral inhibition reflects the activation of molecular layer interneurons, and its major role is to increase the excitability of the activated area by disinhibition. The on-beam inhibition most likely reflects Golgi cell inhibition of granule cells. However, Purkinje cell collateral inhibition of Golgi cells cannot be excluded. Both possibilities suggest that the role of the on-beam inhibition is to efficiently modulate, in time and space, the mossy fiber input to the cerebellar cortex.

Animals↗

PubMed2003

Axonal pathways to the lateral superior olive labeled with biotinylated dextran amine injections in the dorsal cochlear nucleus of rats.

The lateral superior olive (LSO) contains cells that are sensitive to intensity differences between the two ears, a feature used by the brain to localize sounds in space. This report describes a source of input to the LSO that complements bushy cell projections from the ventral cochlear nucleus (VCN). Injections of biotinylated dextran amine (BDA) into the dorsal cochlear nucleus (DCN) of the rat label axons and swellings in several brainstem structures, including the ipsilateral LSO. Labeling in the ipsilateral LSO was confined to a thin band that extended throughout the length of the structure such that it resembled an LSO isofrequency lamina. The source of this labeled pathway was not obvious, because DCN neurons do not project to the LSO, and VCN bushy cells were not filled by these injections. Filled neurons in several brainstem structures emerged as possible sources. Three observations suggest that most of the axonal labeling in the LSO derives from a single source. First, the number of labeled VCN planar multipolar cells and the amount of labeling in the LSO were consistent and robust across animals. In contrast, the number of labeled cells in most other structures was small and highly variable. Second, the locations of planar cells and filled axons in the LSO were related topographically to the position of the DCN injection site. Third, labeled terminal arborizations in the LSO arose from collaterals of axons in the trapezoid body (output tract of planar cells). We infer that planar multipolar cells, in addition to bushy cells, are a source of ascending input from the cochlear nucleus to the LSO.

Animals↗

PubMed1981

Mechanism of resistance of variants of the Lewis lung carcinoma to N-(phosphonacetyl)-L-aspartic acid.

Variants of the Lewis lung carcinoma were selected for resistance to N-(phosphonacetyl)-L-aspartic acid (PALA) by treatment of tumor-bearing mice with repetitive subcurative doses of PALA. The specific activity of the target enzyme, L-aspartic acid transcarbamylase (ATCase), was measured in the four variants developed. Three had markedly elevated ATCase activities; however, the fourth line, LL/PALA-C, had an ATCase activity identical to that of the parent, PALA-sensitive line (LL/O). One high-ATCase variant, LL/PALA-J, and LL/PALA-C were compared with LL/O in subsequent biochemical studies on the mechanism of resistance to PALA. Enzyme activities in the salvage pathways which phosphorylate pyrimidine nucleosides and deoxynucleosides were found to be similar in all three lines. ATCase in these lines exhibits closely comparable kinetics with its natural substrates as well as with PALA. The time courses of restitution of ATCase after a single therapeutic dose of PALA show that both resistant variants recover full activity more rapidly than the parent. Additionally, inhibition of ATCase 24 hr following graded doses of PALA is lower in the resistant lines. The uptake of [14C]PALA in vitro into cell lines derived from the three Lewis lung carcinomas apparently occurs by passive diffusion and at comparable rates in both sensitive and resistant cells. Analysis of the nucleotide content of tumors reveals comparable spectrums of purine and pyrimidine nucleotide levels in the LL/O and LL/PALA-C lines, whereas the LL/PALA-J line has augmented nucleotide pools. In all three lines, 24 hr after treatment with PALA (400 mg/kg), uridine and cytidine nucleotide levels were substantially diminished (70 to 80%) while adenosine 5'-triphosphate and guanosine 5'-triphosphate levels were elevated (50 to 100%). Estimations of precursor flux through the de novo pyrimidine pathway by measuring orotate and orotidine levels in tumors of mice treated with pyrazofurin (an inhibitor of orotidine-5'-monophosphate decarboxylase) and either 0.9% NaCl solution or PALA shows that PALA treatment eliminates orotate and orotidine accumulation in LL/O but reduces it by only 75 and 50% in LL/PALA-C and LL/PALA-J, respectively. Similarly, PALA treatment (20 microM) of tumor lines in culture provokes a dramatic decrease in the incorporation of NaH14CO3 into pyrimidine intermediates and nucleotides in the LL/O cell line only. Determinations of specific activities of the other enzymes in this pathway reveal that the activity of carbamyl phosphate synthetase II, the rate-limiting step, is elevated 2- to 3-fold in both resistant lines. Since carbamyl phosphate synthetase II exists as a complex with ATCase, the suggestion is made that levels of carbamyl phosphate synthetase II are collaterally important determinants of PALA activity. An augmented pool of carbamyl phosphate in the resistant variants may serve to competitively displace PALA from ATCase, diminish enzyme inhibition, and allow pyrimidine biosynthesis to proceed despite therapy.

Amides↗

PubMed1998

Transcranial Doppler: state of the art.

INTRODUCTION: Transcranial color Doppler sonography permits the accurate assessment of intracranial arteries. The latest Doppler units, using the color and power techniques, can show even very small flow volumes (1 x 1 mm). Low frequency (2-2.5 MHz) and very focused transducers are used in transcranial color Doppler. The skull is a very strong barrier for ultrasounds, which requires the use of some acoustic windows like some thin portions of the skull bone or some natural skull foramina. The use of echocontrast agents in color Doppler seems to increase the applications of transcranial studies. OBJECTIVE: (1) To report on transcranial color Doppler technique and findings. (2) To assess the role of contrast agents in the visualization of intracranial vessels. (3) To define the main indications of this technique. MATERIAL AND METHODS: The temporal, the orbital and the suboccipital are the main acoustic windows used for transcranial color Doppler studies. We use phased-array transducers (2-2.5 MHz) and, preferrably, the echocontrast agent. We examined 15 patients with severe internal carotid artery stenoses after the infusion of Levovist (Schering AG, Berlin, Germany) suspension (8 ml at 300 mg Galactose/ml, infused at 0.5 ml/s). RESULTS: Levovist infusion permitted to depict the main intracranial vessels in all cases. The middle and the anterior cerebral arteries are shown through the temporal window. The former is the main cerebral artery, it is the easiest to identify and presents the highest peak systolic velocity. The orbital window can be used to visualize the ophthalmic artery and the internal carotid artery siphon, while the vertebral and the basilar arteries are demonstrated through the suboccipital window. DISCUSSION: We report the most important findings and discuss the main indications of transcranial color Doppler studies. In addition to flow presence and direction, the main indices of arterial flow can be measured thanks to contrast agent administration, namely the peak systolic velocity, the end diastolic velocity, the resistance index and the pulsatility index. A morphological assessment of the Willis circle can also be carried out with color and power Doppler. Functional studies can be performed to assess the residual autoregulatory function of the cerebral circle in the patients with internal carotid artery stenosis or occlusion. The development of intracranial collateral circles can also be studied in these patients. Moreover, the M1 segment of the middle cerebral artery and the internal carotid artery siphon can be demonstrated directly. Transcranial color Doppler is also a useful tool to detect vasospasm after subarachnoid hemorrhage and to monitor blood flow velocity in the middle cerebral artery during carotid endarterectomy. The assessment of blood supply to arteriovenous malformations and to intracranial neoplasms is another application. CONCLUSION: With reference to internal carotid stenoses, the main applications of transcranial color Doppler are the study of intracranial vessels, of intracranial arterial stenosis, of arteriovenous malformations and of Willis circle aneurysms, as well as the monitoring of blood flow velocity during carotid endarterectomy. Echocontrast agents play an important role in the visualization of intracranial vessels.

Arterial Occlusive Diseases↗

PubMedDate not supplied

[Comparative evaluation of echography, computerized tomography and magnetic resonance imaging in the diagnosis of hepatocellular carcinoma in cirrhotic patients].

The contribution of US, CT, and MR imaging was investigated in 25 cirrhotic patients with hepatocellular carcinoma. The following parameters were considered: lesion detection, site and size of the lesion, daughter nodules, location and/or infiltration of intrahepatic vessels, patency of portal vein and collateral vessels, signs of chronic liver disease, steatosis, ascitis, and lymphadenopathy. Our results confirm the value of US, which also allowed lesion biopsy in all cases. CT was as accurate as US in detecting the lesion and even superior in demonstrating daughter nodules. MR imaging, with conventional SE and IR sequences, was inferior since it missed 3 lesions due to motion artifacts; moreover, a smaller number of daughter nodules was seen than with CT. The authors conclude that, at present, MR imaging cannot replace US and CT; the latter, if combined with arteriography, using either hydrosoluble or liposoluble contrast agents, gives the best results in the detection of small hepatocellular carcinomas, and especially of daughter nodules which are important factors for planning appropriate therapy.

Carcinoma, Hepatocellular↗

PubMed1999

Angiographic criteria reliably predict when carotid endarterectomy can be safely performed without a shunt.

BACKGROUND: Selective shunting during carotid endarterectomy is widely performed, but the optimal approach for predicting when a shunt is unnecessary remains uncertain. We evaluated the ability of preoperative cerebral angiography to predict when carotid endarterectomy could be safely performed without a shunt. STUDY DESIGN: Eighty-seven patients undergoing carotid endarterectomy between August 1991 and December 1997 had preoperative cerebral angiograms. The angiograms were evaluated for the presence of collateral flow from the contralateral carotid through the anterior communicating artery and from the posterior circulation through the posterior communicating artery. Patients then underwent endarterectomy and were selectively shunted based on somatosensory evoked potential changes. Internal carotid artery stump pressure was routinely measured in all patients. RESULTS: Nine patients (10%) had a shunt placed based on somatosensory evoked potential changes and none of the 87 patients had a perioperative (30 days) stroke. Angiography revealed that 36 patients (41%) had no cross-filling from the contralateral carotid through the anterior communicating artery. Nine of these patients (25%) required a shunt; none of the 51 patients with adequate cross-filling (p < 0.001) did. Furthermore, 94% of the patients without cross-filling but with a patent ipsilateral posterior communicating artery did not require a shunt using somatosensory evoked potential changes as the standard for shunt insertion. Stump pressure measurements (> or = 25 mmHg) or (> or = 50 mmHg) did not reliably exclude the need for a shunt. Only 2 of 15 patients with contralateral carotid occlusion and 1 of 16 patients with a prior ipsilateral stroke required shunts. CONCLUSIONS: In the presence of cross-filling from the contralateral carotid artery, shunt insertion was uniformly unnecessary. In addition, routine shunting of patients with previous ipsilateral strokes or contralateral carotid occlusion was not always necessary. Stump pressures were less sensitive than angiographic criteria in determining when a shunt was unnecessary. Evaluation of cross-filling from the contralateral carotid artery on preoperative angiography can predict with certainty which patients will not require a shunt.

Aged↗