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Results for “Collateral sensitivity”

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At least 1,423 records · Page 79Linked to original sources

PubMed1997

Metabotropic glutamate receptor mediated long-term depression in developing hippocampus.

The effects of bath application of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 10 microM) were studied at the Schaffer collateral-CA1 synapse in hippocampal slices from rats of 8-33 days postnatal age. In immature animals (8-12 days) ACPD induced a biphasic response characterized by an acute decrease in field EPSP slope (approximately 50-60% of baseline) in the presence of the agonist, followed by long-term depression (LTD, approximately 75-80% of baseline) after washout. In animals older than 20 days, ACPD induced a slow onset potentiation or minimal change. Both the acute depression and LTD were blocked by the mGluR antagonist alpha-methyl-4-carboxyphenyl glycine (MCPG). ACPD-induced LTD was blocked by the N-methyl-D-aspartate receptor (NMDAR) antagonists D(-)-2-amino-5 phosphopentanoic acid (AP5) and dizocilpine maleate (MK-801), and by ethanol. Glutamic pyruvic transaminase, an enzyme that selectively metabolizes endogenous extracellular glutamate, also blocked LTD suggesting that the requisite NMDA currents were tonically activated by extracellular rather than synaptically released glutamate. ACPD-induced LTD was blocked by staurosporine, indicating a requirement for serinethreonine kinase activation, and was unaffected by the L-type voltage sensitive calcium channel blocker nitrendipine and the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT). Because mGluR-mediated LTD was observed only in immature CA1, mGluRs may play a role in hippocampal development, perhaps by contributing to synapse pruning in a temporally restricted fashion.

Animals↗

PubMed1980

[Induced coronary spasm: immediate revascularization by the opposite coronary artery. Use of myocardial scintigraphy].

The case reported analyses the instantaneous revascularisation distal to a coronary spasm by electrocardiography and thallium scintigraphy. The patient, a 48 year old man, had an 18 months history of spontaneous anginal chest pain sensitive to trinitrin. No electrocardiogrammes had been recorded during an attack. Coronary angiography was normal apart from a slight reduction in calibre of a dominant right coronary artery. Injection of 0.4 mg methylergometrine provoked an occlusive spasm of this artery after 4 minutes. At the same time the patient experienced angina and 4,5 mm depression of the ST segment, without ST changes in D3 and AVF, was observed. Opacification of the left coronary artery during spasme of the right showed retrograde revascularisation of the posterior interventricular artery which was reversed when the coronary spasm was terminated with trinitrin. Thallium scintigraphy was performed during another spasm provocation test four days later which gave identical clinical and electrical changes. A zone of hypofixation with blurred limits over the inferior myocardial wall was demonstrated. In the absence of ST elevation and of lacuna on myocardial scanning, the myocardial ischaemia induced by this occlusive spasm could not be considered to be total. Therefore the immediate revascularisation of the coronary artery in spasm seemed to have played the role of an effective collateral circulation.

Angina Pectoris↗

PubMed2006

[Curved planar reformations in multi-slice spiral CT in pancreatic adenocarcinoma: prediction of invasion of pancreatic and peripancreatic ductal structures].

OBJECTIVE: To investigate the clinical values of the curved planar reformation (CPR) in multi-slice spiral CT (MSCT) in determining the malignant invasion of pancreatic carcinoma into the intrapancreatic and peripancreatic ductal structures. METHODS: Thirty-seven patients having documented pancreatic carcinoma with tumor involvement of intrapancreatic or peripancreatic ductal structures were enrolled. All patients received dual-phase MSCT scan of upper abdomen. Images generated by CPR technique were used for evaluating the appearances of intrapancreatic and peripancreatic ductal structures. RESULTS: Malignant invasion of peripancreatic arteries was found in 28 patients and characterized by: obliteration of fat plane between tumor and the artery, with contact surface of more than 180 degrees; stenosis or deformation of the artery; and infarction of the spleen. Invasion of peripancreatic veins was found in 31 patients and characterized by: tumor encasement of the vein, resulting in the narrowing or deformation of the vein; lack of enhancement of the involved venous segment; tumor thrombosis in the venous lumen; and formation of collateral circulation. Invasion of intrapancreatic segment of the common bile duct or pancreatic duct was found in 18 patients and characterized by: sudden interruption of the bile duct or pancreatic duct; narrowing of the bile duct or pancreatic duct; and dilation of the up-stream ducts proximal to the involvement portion. CPR images clearly depicted the direct relationship between tumor mass and the involved ductal structures. CONCLUSION: Invasion of intrapancreatic or peripancreatic ductal structures by pancreatic carcinoma has certain MSCT imaging features. CPR technique is valuable in depicting these imaging findings.

Adenocarcinoma↗

PubMed1996

Diagnostic criteria for transcranial colour-coded duplex sonography evaluation of cross-flow through the circle of Willis in unilateral obstructive carotid artery disease.

A transcranial colour-coded duplex sonography (TCCD) study was performed to establish reliable criteria for the assessment of collateral flow through the anterior (ACoA) and posterior (PCoA) communicating artery without using compression tests. We studied 86 patients with angiographically evaluated unilateral > 69% stenosis (n = 53) and occlusion (n = 33) of the carotid artery. The following TCCD criteria were evaluated: for diagnosis of cross-flow through the ACoA, detection of reversed flow in the anterior cerebral artery (ACA) on the obstructed (ipsilateral) side. For the diagnosis of cross-flow through the PCoA: (A) identification of the PCoA; (B) peak systolic velocity in P1 posterior cerebral artery (PCA) higher than the mean value + 2 SD of normals; (C) ratio of ipsilateral peak systolic P1 PCA velocity to peak systolic P1 PCA velocity to peak systolic P2 PCA velocity higher than the mean ratio + 2 SD of normals; (D) ratio of ipsilateral peak systolic P1 PCA velocity to contralateral peak systolic P1 PCA velocity higher than the mean ratio + 2 SD of normals; (E) peak systolic basilar artery velocity higher than the mean value + 2 SD of normals. Eight patients (9%) with inadequate temporal ultrasonic windows were excluded. The sensitivity and specificity for TCCD evaluation of ACoA cross-flow were 100%. Using criteria A and B the corresponding values for the PCoA were 85 and 98%, respectively. Criteria C-E were not useful owing to lower sensitivity. In conclusion, we delineated TCCD criteria that make it possible to assess reliably the cross-flow through the circle of Willis in patients with adequate ultrasonic windows.

Adult↗

PubMed1997

Fundus fluorescein angiography of patients with severe hypertensive nephropathy.

PURPOSE: To analyze the fluorescein angiograms of patients with hypertensive renal failure. METHODS: Fluorescein angiograms were obtained of 34 patients with hypertensive renal failure. The glomerular filtration was less than 20 ml/min in each patient. RESULTS: Capillary nonperfusion and a coarse retinal capillary bed are the hallmark of the hypertensive retinopathy. Tortuous retinal arterioles or tortuous retinal arteriovenous anastomoses are observed. It is suggested that capillary collaterals shunt arteriolar obstructions or short-cut nonperfused capillary beds; these remodel into tortuous arterioles or arteriovenous anastomoses with regular caliber. Elschnig spots and delayed choroidal filling are signs of hypertensive choroidopathy. Depigmentation spots of the retinal pigment epithelium without a central pigment clump are considered atypical Elschnig spots. CONCLUSIONS: Retinal pigment epithelial changes are permanent scars of hypertensive choroidopathy, while coarse retinal capillary bed and tortuous retinal arterioles or arteriovenous anastomoses are the result of hypertensive retinopathy in these patients with hypertensive renal failure.

Adult↗

PubMed1999

Utility, safety, and accuracy of intraoperative angiography in the surgical treatment of aneurysms and arteriovenous malformations.

BACKGROUND AND PURPOSE: The role of intraoperative angiography in the treatment of neurovascular lesions has remained extremely controversial. We retrospectively reviewed the utility, safety, and accuracy of intraoperative angiography to ascertain its effect on the treatment of patients with neurovascular lesions. METHODS: We reviewed the results of intraoperative angiography in 91 patients treated surgically for intracranial aneurysms and in 98 patients treated surgically for arteriovenous malformations (AVMs). All treatments were completed at two major teaching hospitals between October 1987 and March 1995. RESULTS: The initial angiographic findings caused the surgical procedure to be modified in 24 (26%) of the patients with aneurysms and in 28 (29%) of the patients with AVMs. Analysis of the final angiographic sequence showed residual lesions in nine (10%) of the aneurysm cases and in eight (8%) of the AVM cases. The imperfect angiographic results were deemed acceptable because there was either evidence of collateral flow when the parent vessel was occluded or the risk of further surgical modification was considered more dangerous than the abnormality itself. Seven patients suffered complications, of which only one had permanent neurologic sequelae: a CNS complication rate of 0.5%. Comparison of the intraoperative angiographic findings with those of postoperative studies revealed four false-negative results (5.2%). CONCLUSION: Intraoperative angiography is an important component in the treatment of patients with intracranial vascular lesions. It is effective and can be carried out with low risk in this patient population.

Cerebral Angiography↗

PubMed1995

Cardioprotection with the KATP opener cromakalim is not correlated with ischemic myocardial action potential duration.

We endeavored to determine if the enhanced shortening of the myocardial action potential duration (APD) during ischemia can be dissociated from the cardioprotective effects of the adenosine triphosphate (ATP) sensitive potassium channel (KATP) opener cromakalim. To establish if there is a relationship between APD shortening and the cardioprotective effect of cromakalim, we determined the effect of a dose of the delayed rectifier (IKr) blocker dofetilide (which abolishes the APD shortening effect of cromakalim) on the cardioprotective activity of cromakalim. Cromakalim was infused at a previously determined cardioprotective dose (10 micrograms/kg + 0.3 micrograms/kg/min infusion i.c.), and we determined the effect of 1 mg/kg (followed by a 0.01 mg/kg/min i.v. infusion) dofetilide alone and in combination with cromakalim on APD shortening and infarct size (90-min coronary occlusion and 5-h reperfusion) in anesthetized dogs. Dofetilide completely abolished the APD shortening effects of cromakalim during ischemia such that APD was similar to preischemic values. Cromakalim only shortened the APD during ischemia, although this effect was attenuated late into ischemia. Cromakalim significantly reduced infarct size (40% reduction from vehicle group value), whereas dofetilide alone had no effect. Dofetilide, at a dose that prevented the cromakalim-induced shortening of APD in ischemic tissue, did not attenuate the cardioprotective effects of cromakalim. No differences in collateral blood flow for any of the groups were observed. Dofetilide did cause a slight bradycardia, but this effect is unlikely to affect the interpretation of the results. These data suggest that APD shortening observed with the KATP opener cromakalim is not correlated with its cardioprotective effects.

Action Potentials↗

PubMed1995

Face-sensitive regions in human extrastriate cortex studied by functional MRI.

1. We have previously identified face-selective areas in the mid-fusiform and inferior temporal gyri in electrophysiological recordings made from chronically implanted subdural electrodes in epilepsy patients. In this study, functional magnetic resonance imaging (fMRI) was used to study the anatomic extent of face-sensitive brain regions and to assess hemispheric laterality. 2. A time series of 128 gradient echo echoplanar images was acquired while subjects continuously viewed an alternating series of 10 unfamiliar faces followed by 10 equiluminant scrambled faces. Each cycle of this alternating sequence lasted 12 s and each experimental run consisted of 14 cycles. The time series of each voxel was transformed into the frequency domain using Fourier analysis. Activated voxels were defined by significant peaks in their power spectra at the frequency of stimulus alternation and by a 180 degrees phase shift that followed changes in stimulus alternation order. 3. Activated voxels to faces were obtained in the fusiform and inferior temporal gyri in 9 of 12 subjects and were approximately coextensive with previously identified face-selective regions. Nine subjects also showed activation in the left or right middle occipital gyri, or in the superior temporal or lateral occipital sulci. Cortical volumes activated in the left and right hemispheres were not significantly different. Activated voxels to scrambled faces were observed in six subjects at locations mainly in the lingual gyri and collateral sulci, medial to the regions activated by faces. 4. Face stimuli activated portions of the midfusiform and inferior temporal gyri, including adjacent cortex within occipitotemporal sulci.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

Iodine-123-BMIPP imaging in unstable angina: a guide for interventional strategy.

UNLABELLED: The aim of this study was to clarify the clinical implications of decreased myocardial uptakes of 123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) in patients with unstable angina. METHODS: Fatty acid metabolic imaging with 123I-BMIPP was performed in 20 patients with unstable angina during the pain-free state. Regional uptakes of 123I-BMIPP were scored semiquantitatively, and clinical characteristics and angiographic findings were compared between the patients with the normal and abnormal 123I-BMIPP images. RESULTS: There were 9 patients with normal and 11 patients with abnormal 123I-BMIPP images. Severe coronary stenosis exceeding 90% (91% compared with 44%, p < 0.05) and 99% (82% compared with 0%, p < 0.01) and collateral opacification (36% compared with 0%, p < 0.05) were more frequently observed in patients with abnormal 123I-BMIPP images than in those with normal images. Percutaneous transluminal coronary angioplasty or coronary artery bypass grafting was performed in 22% of patients with normal 123I-BMIPP images and in 82% of patients with abnormal 123I-BMIPP images (p < 0.01). CONCLUSION: Fatty acid metabolic imaging with 123I-BMIPP can determine the functional severity of coronary artery disease and is helpful for a clinical judgment in interventional treatment.

Aged↗

PubMed2002

Real-time detection of vascular occlusion and reperfusion of the brain during surgery by using infrared imaging.

OBJECT: Application of sensitive infrared imaging is ideally suited to observe blood vessels and blood flow in exposed organs, including the brain. Temporary vascular occlusion is an important part of neurosurgery, but the capacity to monitor the effects of these occlusions in real time is limited. In surgical procedures that require vascular manipulation, such as those involving aneurysms, arteriovenous malformations (AVMs), or tumors, the ability to visualize blood flow in vessels and their distribution beds would be beneficial. The authors recount their experience in the use of a sensitive (0.02 degrees C), high-resolution (up to 50 microm/pixel) infrared camera with a rapid shutter speed (up to 2 msec/frame) for localizing cortical function intraoperatively. They observed high-resolution images of cerebral arteries and veins. The authors hypothesized that infrared imaging of cerebral arteries, performed using a sensitive, high-resolution camera during surgery, would permit changes in arterial flow to be be seen immediately, thus providing real-time assessment of brain perfusion in the involved vascular territory. METHODS: Cynomolgus monkeys underwent extensive craniectomies, exposing the frontal, parietal, and temporal lobes. Temporary occlusions of the internal carotid artery and middle cerebral artery branches (30 events) were performed serially and were visualized with the aid of an infrared camera. Arteries and veins of the monkey brain were clearly visualized due to cooling of the exposed brain, which contrasted with blood within the vessels that remained at core temperature. Blood flow changes in vessels were seen immediately (< 1 second) in real time during occlusion and reopening of the vessels, regardless of the duration of the occlusion. Areas of decreased cortical blood flow rapidly cooled (-0.3 to 1.3 degrees C) and reheated in response to reperfusion. Rewarming occurred faster in arteries than in the cortex (for a 20-minute occlusion, the change in temperature per second was 2 x 10(-2) degrees C in the artery and 7 x 10(-3) degrees C in the brain). Collateral flow could be evaluated by intraoperative observations and data processing. CONCLUSIONS: Use of high-resolution, digital infrared imaging permits real-time visualization of arterial flow. It has the potential to provide the surgeon with a means to assess collateral flow during temporary vessel occlusion and to visualize directly the flow in parent arteries or persistent filling of an aneurysm after clipping. During surgery for AVMs, the technique may provide a new way to assess arterial inflow, venous outflow, results of embolization, collateral flow, steal, and normal perfusion pressure breakthrough.

Animals↗

PubMed1996

Enhancement of neurite-sprouting by suppression of HPC-1/syntaxin 1A activity in cultured vertebrate nerve cells.

HPC-1/syntaxin 1A is a C-terminal anchored neuronal membrane protein, of which all of the N-terminal regions are located on the intracellular side, and it interacts with presynaptic membrane proteins, synaptic vesicle proteins and soluble N-ethylmaleimide-sensitive fusion protein attachment proteins (SNAPs). HPC-1/syntaxin 1A has been proposed to act as a target SNAP receptor (t-SNARE) in the neuron and contributes to the vesicle docking/fusion process during the fast exocytosis at the presynaptic active zone. However, studies using an electron-microscope revealed that HPC-1/syntaxin 1A distributed not only at the presynaptic region but throughout the whole axonal membrane, and the functions of this axonal HPC-1/syntaxin 1A remain completely unknown. To investigate its physiological role, we attempted to inhibit the function of HPC-1/syntaxin 1A in cultured neural cells by following two methods. First, de novo synthesis of HPC-1/syntaxin 1A was inhibited by an application of antisense oligonucleotide in cultured adult rat dorsal root ganglion (DRG) neurons. Second, antibody against HPC-1/syntaxin 1A was applied intra-axonally in the cultured chick retinal ganglion neuron. Both treatments, which were expected to downregulate the function of HPC-1/syntaxin 1A, consistently elicited an enhancement of the axonal sprouting. These results suggest that the axonal HPC-1/syntaxin 1A would physiologically suppress the excess axon-collateral sprouting. Downregulation of HPC-1/syntaxin 1A expression may underlie the control of collateral sprouting and synapse formation during development and memory processes.

Animals↗

PubMed1993

A selective LTP of NMDA receptor-mediated currents induced by anoxia in CA1 hippocampal neurons.

1. The possibility of long-lasting modifications of glutamatergic responses after anoxic-aglycemic (AA) episodes was investigated in CA1 hippocampal neurons of adult slices. Bicuculline (10 microM) was continuously bath applied to block GABAA receptor-mediated currents. AA episodes were induced by brief (1.30-3 min) perfusions with a glucose free artificial-cerebro-spinal-fluid (ACSF) saturated with 95% N2-5% CO2. 2. In presence of (0.6 mM) Mg2+ and a low concentration of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1 microM), the Schaffer collateral field EPSPs consisted of an early AMPA receptor-mediated component and a late N-methyl-D-aspartate (NMDA) receptor-mediated component. The former was blocked by (10 microM) CNQX and the latter by (50) microM D-2-amino-5-phosphonovalerate (D-APV). The AA episode induced a selective long-term potentiation (LTP) of the NMDA receptor-mediated component [+70 +/- 13% (mean +/- SE), P < or = 0.008, n = 9] without affecting significantly the AMPA receptor-mediated component (+2 +/- 4, P < or = 0.86 n = 9). This selective LTP is due to an enhanced efficacy of synaptic transmission and will be referred to as anoxic LTP. 3. In slices perfused with an ACSF containing a physiological concentration of (1.3 mM) Mg2+ and no CNQX, the intracellularly recorded excitatory postsynaptic potential (EPSP) was mixed (AMPA/NMDA) at -65 mV and exclusively mediated by AMPA receptors at -100 mV. At -65 mV, the AA episode induced a persistent potentiation of the EPSP (peak amplitude potentiated by 43 +/- 6%, P < or = 0.008, n = 9, 1 h after return to control ACSF). This potentiated component of the EPSP was fully sensitive to (50 microM) D-APV. The CNQX-sensitive AMPA receptor-mediated component was not affected by the AA episode (-5.7 +/- 6%, P < or = 0.123, n = 9). Furthermore, at -100 mV a large APV-sensitive component appeared after the AA episode (+58 +/- 18% of the peak amplitude, P < or = 0.018, n = 9). Therefore, the AA episode induced a selective LTP of the NMDA receptor-mediated component of the EPSP. 4. A robust LTP (+50.0 +/- 7.5%, P < or = 0.008, n = 12) of the NMDA receptor-mediated intracellular EPSP was also observed when AMPA receptors were fully and continuously blocked by (15 microM) CNQX.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons.

We examined the effects of the chemokine fractalkine (CX3CL1) on EPSCs evoked by electrical stimulation of Schaffer collaterals in patch-clamped CA1 pyramidal neurons from rat hippocampal slices. Acute application of CX3CL1 caused a sustained reduction of EPSC amplitude, with partial recovery after washout. CX3CL1-induced EPSC depression is postsynaptic in nature, because paired-pulse ratio was maintained, amplitude distribution of spontaneous excitatory postsynaptic currents shifted to lower values, and whole-cell current responses to AMPA were reversibly inhibited. EPSC depression by CX3CL1 is mediated by CX3CL1 receptor (CX3CR1), because CX3CL1 was unable to influence EPSC amplitude in CA1 pyramidal neurons from CX3CR1 knock-out mice. CX3CL1-induced depression of both EPSC and AMPA current was not observed in the absence of afferent fiber stimulation or AMPA receptor activation, respectively, indicating the requirement of sustained receptor activity for its development. Findings obtained from hippocampal slices, cultured hippocampal neurons, and transfected human embryonic kidney cells indicate that a Ca2+-, cAMP-, and phosphatase-dependent process is likely to modulate CX3CL1 effects because of the following: (1) CX3CL1-induced depression was antagonized by intracellular BAPTA, 8Br-cAMP, phosphatase inhibitors, and pertussis toxin (PTX); (2) CX3CL1 inhibited forskolin-induced cAMP formation sensitive to PTX; and (3) CX3CL1 inhibited forskolin-induced Ser845 GluR1 phosphorylation, which was sensitive to PTX and dependent on Ca2+ and phosphatase activity. Together, these findings indicate that CX3CL1 negatively modulates AMPA receptor function at active glutamatergic synapses through cell-signaling pathways by influencing the balance between kinase and phosphatase activity.

Animals↗

PubMed2003

Allergic and pseudoallergic reactions induced by glucocorticoids: a review.

Glucocorticoids (GCs) represent the most effective treatment for autoimmune and allergic diseases, even if collateral effects are not rare, especially endocrine and immunosuppressive manifestations. Moreover, these drugs can develop adverse immunological reactions of I, III or IV type. Though immediate adverse reactions caused by systemic therapy with GCs are not very frequent, the possible beginning of anaphylactic and pseudo-anaphylactic manifestations in patients undergoing therapy with these drugs has to be considered. It has been observed that immediate adverse reactions usually are happened in asthmatic patients and in patients obliged to assume GCs again and again because of their pathology (e.g, kidney transplant). Other risk factors resulted to be female sex and hypersensibility to acetylsalicylic acid (ASA). Both in the cases of pseudo-allergic and allergic reactions, the pharmacological principle is hardly the responsible agent for the reaction; instead the excipients in drugs are often implicated (succinate salt, sulphites and carboxy-methyl-cellulose). It is possible that the IgE-response is highly specific for a fixed GC molecule as well depending on the way of administration and its salification. Moreover, it has been hypothesized that in patients with a first type allergic reaction to GCs there is a fourth type, sensitization to GCs, which is not usually diagnosed and even comes before IgE sensitization. Third type hypersensibility reactions may occur, too. Since GCs are large-scale drugs, also in emergency medicine and reanimation, allergic sensitization towards them, although infrequent, gives many interventionist problems. In the light of this feature, it seems of crucial importance to verify the tolerance toward other GC molecules. And in particular, it has been noted that patients presenting immediate reactions to hydrocortisone (HC) and methylprednisolone (MP) could tolerate prednisone and prednisolone per os and second-generation GCs, such as desamathazone and betamethazone. Nevertheless, second-generation GCs must not be considered safe; in fact, the beginning of allergic manifestations has been pointed out even towards them.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Extent of pathologic invasion of the inferior vena cava in resected liver cancer compared with possible caval invasion diagnosed by preoperative images.

The extent of cancerous invasion of the inferior vena cava (IVC) determined from resected liver cancer was examined pathologically. Ten patients presenting with liver cancer (metastatic liver cancer, five patients; hepatocellular carcinoma, three; and cholangiocellular carcinoma, two) were diagnosed with positive IVC invasion using preoperative imaging techniques of extracorporeal ultrasonography, computed tomography, magnetic resonance imaging, and vena cavography. The diagnostic criterion for positive IVC invasion by preoperative imaging was longitudinal IVC compression measuring over 50 mm, or transverse IVC compression extending to more than half the circumference of the IVC, or the presence of lesions protruding into the IVC lumen, or the presence of developed collateral veins. All patients underwent combined resection of the IVC. However, pathology results revealed that four of the ten patients had no cancerous invasion of the IVC, and that the extent of invasion along both the longitudinal and transverse axes of the IVC was much smaller than the compression shown by imaging results. We believe that detailed preoperative assessment, using a more precise imaging technique, as well as further intraoperative examination, is required to predict the full pathological extent of cancerous invasion of the IVC.

Aged↗

PubMed2002

Medical imaging techniques in the evaluation of strategies for therapeutic angiogenesis.

Recent advancements in our understanding of the basic biology of angiogenesis have prompted a focus on practical applications, both in cardiovascular disease and in oncology. The focus on practical applications has stimulated development of novel noninvasive tools that provide serial assessment of ongoing vessel growth in vivo. Nuclear imaging (SPECT, PET) and x-ray angiography have been used to assess changes in perfusion and anatomic appearance, respectively, after induced neovascular development. New MRI techniques provide the ability to identify early changes in vivo that are more sensitive to detection of the effects of new vessel growth than x-ray angiography or nuclear imaging. These new MRI techniques include measurement of blood delivery to the myocardium, development of intramyocardial vasculature, and incremental changes in regional myocardial contractile function. With the combination of methods now available, we expect to be able to track key steps of angiogenesis in vivo and to assess the efficacy of angiogenic therapies. These new imaging capabilities offer crucial information which we hope will hasten the identification and deployment of effective pharmaceutical therapies as an adjunct or alternative to invasive treatments of ischemic disease by targeted stimulation of angiogenesis, and of cancer, by targeted inhibition of angiogenesis.

Animals↗

PubMed1996

Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: ultrastructural morphometric analysis of axonal alterations.

Polyethylene cuffs of varying inner diameters were applied to the rat sciatic or sural nerve with the aim of inducing a standardized nerve injury, as assessed by morphometric analyses of fiber-size spectrum alterations, associated with behavioral manifestations of neuropathic pain. The temporal sequence of axonal degeneration and regeneration was examined in parallel with behavioral analyses of pain initiation and recovery over a 6-week postoperative (PO) period. Cuffs of 0.028-0.030" inner diameter loosely enclosed sciatic nerves of young rats and elicited relatively uniform axonal degeneration and 'pain'. Large myelinated axons underwent an early and sustained numerical depletion. Both the thinly myelinated and unmyelinated axon populations were initially diminished, but later rose to levels significantly greater than control values, likely the result of: (1) demyelination, (2) early stages of remyelination, (3) regenerative sprouting, and/or (4) collateral sprouting of undamaged unmyelinated axons. Pathological alterations of the injured nerve included edematous swelling, hypertrophy of the perineurial sheath, infiltration of fibroblasts and collagen into the intraneurial compartment, increasing interaxonal space and decreasing order and density of axonal packing. Animals displayed maximal pain-related behaviors, including gait and postural asymmetries and hypersensitivity to mechanical compression and cold, during the 2nd week PO and had largely recovered by approximately 4 weeks PO. Consistent behavioral manifestations of pain were achieved over a wide range of fiber spectrum alteration; however, with the largest cuffs or 'bracelets' used in this study, a substantial axonal fiber spectrum change was produced without inducing pain-related behavior, suggesting that decrement in the number of myelinated axons was not always sufficient to elicit pain. Similar morphometric and pathological results were achieved with sural neuropathy after 0.010" ID cuffs and 14 days PO survival. Considering the lack of correlation between axonal alterations and pain, modification in the local intraneurial microenvironment at the site of injury may be a key component of peripheral pain mechanisms; these include changes in the biochemical milieu, increased intraneurial pressure, and altered nociceptor sensitivity or impulse propagation in the relatively intact unmyelinated axon population.

Animals↗

PubMed1999

Ca2+ store-dependent potentiation of Ca2+-activated non-selective cation channels in rat hippocampal neurones in vitro.

1. Potentiation of calcium-activated non-selective cation (CAN) channels was studied in rat hippocampal neurones. CAN channels were activated by IP3-dependent Ca2+ release following metabotropic glutamate receptor (mGluR) stimulation either by Schaffer collateral input to CA1 neurones in brain slices in which ionotropic glutamate and GABAA receptors, K+ channels, and the Na+-Ca2+ exchanger were blocked or by application of the mGluR antagonist ACPD in cultured hippocampal neurones. 2. The CAN channel-dependent depolarization (DeltaVCAN) was potentiated when [Ca2+]i was increased in neurones impaled with Ca2+-containing microelectrodes. 3. Fura-2 measurements revealed a biphasic increase in [Ca2+]i when 200 microM ACPD was bath applied to cultured hippocampal neurones. This increase was greatly attenuated in the presence of Cd2+. 4. Thapsigargin (1 microM) caused marked potentiation of DeltaVCAN in CA1 neurones in the slices and of the CAN current (ICAN) measured in whole cell-clamped cultured hippocampal neurones. 5. Ryanodine (20 microM) also led to a potentiation of DeltaVCAN while neurones pretreated with 100 microM dantrolene failed to show potentiation of DeltaVCAN when impaled with Ca2+-containing microelectrodes. 6. The mitochondrial oxidative phosphorylation uncoupler carbonyl cyanide m-chlorophenyl hydrazone (2 microM) also caused a potentiation of DeltaVCAN. 7. CAN channels are subject to considerable potentiation following an increase in [Ca2+]i due to Ca2+ release from IP3-sensitive, Ca2+-sensitive, or mitochondrial Ca2+ stores. This ICAN potentiation may play a crucial role in the 'amplification' phase of excitotoxicity.

Animals↗