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PubMed1999

Cardiac electron-beam CT in children undergoing surgical repair for pulmonary atresia.

PURPOSE: To study whether electron-beam computed tomography (CT) is as accurate as conventional angiocardiography for the characterization of the true pulmonary arteries and the aortopulmonary collateral vessels in children undergoing surgical correction for pulmonary atresia. MATERIALS AND METHODS: Twenty-three children with pulmonary atresia underwent 48 cardiac-triggered dynamic contrast material-enhanced electron-beam CT studies. Correlation was made with surgical findings in all patients and with 34 cineangiocardiograms. Data from reconstructed electron-beam CT images and cineangiocardiograms were reviewed for the presence, caliber, and origin of true pulmonary arteries and aortopulmonary collateral vessels; for stenosis; for thrombosis; and for the patency of vascular conduits and shunts. RESULTS: Electron-beam CT was more sensitive than angiography in the identification of hypoplastic and/or nonconfluent branch pulmonary arteries, coronary anomalies, conduit and shunt thrombosis, and other postoperative complications, but it was less sensitive in the demonstration of stenoses at collateral vascular origins and anastomoses. Overall test parameters for electron-beam CT and angiography to characterize pulmonary vascularity were similar (sensitivity, 0.94 vs 0.90; specificity, 0.99 for both; accuracy, 0.97 vs 0.95). Three-dimensional reconstructions, although they were helpful in conveying electron-beam CT findings to referring cardiologists and surgeons, did not add diagnostic information to that displayed on images of the transverse sections. CONCLUSION: Electron-beam CT complements conventional diagnostic angiocardiography in preoperative evaluation, especially in the detection of hypoplastic pulmonary arteries. It is well suited for postoperative shunt surveillance.

Adolescent↗
PubMed2000

Retinoic-acid-resistant neuroblastoma cell lines show altered MYC regulation and high sensitivity to fenretinide.

BACKGROUND: High-dose, pulse-13-cis-retinoic acid (13-cis-RA) given after intensive cytotoxic therapy improves event-free survival for high-risk neuroblastoma (NB), but more than 50% of patients have tumor recurrence. PROCEDURE: We conducted multistep selection for resistance to all-trans-retinoic acid (ATRA) in NB cell lines with (SMS-KCNR and LA-N-5) or without (SMS-LHN) MYCN genomic amplification. RESULTS: After 12 exposures to 10 microM ATRA, the two MYCN-amplified cell lines (KCNR 12X RR and LA-N-5 12X RR) showed partial resistance to the cytostatic/differentiation effects of ATRA; complete resistance was seen in LHN 12X RR. ATRA-selected cells showed general RA resistance (cross-resistance to 13-cis-RA). Transient (KCNR 12 X RR, LA-N-5 12X RR) or sustained (LHN 12X RR) novel overexpression of c-myc was associated with RA resistance. RA-insensitive overexpression of MYCN by transduction in SMS-LHN also conferred RA resistance. Both parental and RA-resistant lines showed 2-4 logs of cell kill in response to N-(4-hydroxyphenyl)retinamide (4- HPR, fenretinide). Compared to parental lines, 4-HPR achieved 1-3 log greater cell kills in RA-resistant LHN 12X RR, LA-N-5 12X RR, KCNR 12X RR, and MYCN-transduced SMS-LHN or SK-N-RA. NB cell lines (n = 26) from 21 different patients showed that 16 of 26 (62%) were sensitive to 4-HPR (LC(90) < 10 microM), including lines established at relapse after myeloablative and/or 13-cis-RA therapy. CONCLUSION: Thus, RA-resistant NB cell lines can be sensitive (and in some cases collaterally hypersensitive) to 4-HPR.

Antineoplastic Agents↗
PubMed1980

Biomechanic studies reinserting the medial collateral ligament to correct a chronic anteromedial instability of the knee joint.

One possibility to correct a chronic anteromedial instability of the knee joint is the osseous reinsertion and tightening of the medial collateral ligament. In experiments with a string model and strain gauges attached to the ligaments we investigated the advantages and/or disadvantages of the femoral and tibial reinsertion. Regarding the tension mechanism the medial collateral ligament reacts considerably more sensitivity to the femoral reinsection in proximal-dorsal direction than to the tibial-reinsertion in distal-ventral direction. An accurate knee flexion between 40 and 60 degrees has to be provided reinserting the ligament in proximal-dorsal direction to avoid excessive tension and resulting destruction of the ligament. However the reinsertion of the ligament in distal-ventral direction, independently from the flexion of the knee, always approximates the natural tension of the anterior and posterior margin of the untreated ligament. Biomechanically the reinsertion in distal-ventral direction to tighten the loose ligament seems to be preferable to the reinsertion in proximal-dorsal direction.

Biomechanical Phenomena↗
PubMed2001

Retinoid therapy of childhood cancer.

In vitro studies that showed RA could cause growth arrest and differentiation of myelogenous leukemia and neuroblastoma led to clinical trials of retinoids in APL and neuroblastoma that increased survival for both of those diseases. In the case of APL, ATRA has been the drug of choice, and preclinical and clinical data support direct combinations of ATRA with cytotoxic chemotherapy. For neuroblastoma, a phase I study defined a dose of 13-cis-RA, which was tolerable in patients after myeloablative therapy, and a phase III trial that showed postconsolidation therapy with 13-cis-RA improved EFS for patients with high-risk neuroblastoma. Preclinical studies in neuroblastoma indicate that ATRA or 13-cis-RA can antagonize cytotoxic chemotherapy and radiation, so use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. A limitation on the antitumor benefit of ATRA in APL is the marked decrease in drug levels that occurs during therapy as a result of induction of drug metabolism, resulting in a shorter drug half-life and decreased plasma levels. Although early studies sought to overcome the pharmacologic limitations of ATRA therapy in APL, the demonstration that ATO is active against APL in RA-refractory patients has led to a focus on studies employing ATO. Use of 13-cis-RA in neuroblastoma has avoided the decreased plasma levels seen with ATRA. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cis-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase I trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development.

Antineoplastic Agents↗
PubMed1997

Response of native and stimulated collateral vessels to serotonin.

Previous studies suggest that collateral vessels constrict in response to serotonin. The objective of these studies was to directly measure responses of native and stimulated collateral vessels 30-400 microns in diameter to serotonin and to determine the mechanisms involved in responses to serotonin. Serotonin was suffused onto the left ventricle of dogs, and microvascular diameters were measured with computer-controlled stroboscopic illumination coupled to a microscope-video system. Stimulated collateral vessels and arterioles in collateral-dependent myocardium were measured after Ameroid constriction of the left circumflex artery. Noncollateral and native collateral vessels were examined in dogs without a constrictor. Serotonin produced dose-dependent dilation of noncollateral vessels that was decreased in native collateral vessels, stimulated collateral vessels, and vessels in collateral-dependent myocardium. Dilation in response to nitroprusside was similar in all groups. Dilation in response to serotonin was enhanced by inhibition of 5-hydroxytryptamine (5-HT)2 receptors with ketanserin and blocked by nonselective 5-HT1 and 5-HT2 receptors with methiothepin. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine decreased dilation in response to serotonin. Thus collaterals and arterioles in collateral-dependent myocardium are less sensitive to the dilating effect of serotonin. Responses to serotonin involve a balance between dilation mediated by 5-HT1 receptors and constriction mediated by 5-HT2 receptors.

Animals↗
PubMed1993

Estramustine depolymerizes microtubules by binding to tubulin.

To investigate the mechanism of action of the antineoplastic drug estramustine, we compared its effects on human prostate cancer cells with those of vinblastine. At their respective concentrations that result in 50% inhibition of clonogenic growth, both drugs caused an accumulation of cells blocked at mitosis and similar dose- and time-dependent depolymerization of interphase microtubules. Also, colcemid-resistant and colcemid-hypersensitive Chinese hamster ovary cells with tubulin mutations were collaterally cross-resistant or -sensitive to estramustine. Thus, the cytotoxicity of estramustine is due to its microtubule depolymerization properties. This could be caused by interaction with tubulin and/or with microtubule-associated proteins (MAPs). Previous investigations have shown that high concentrations of estramustine phosphate can inhibit microtubule polymerization in vitro by binding to MAPs. However, estramustine phosphate is the clinical prodrug to estramustine, the intracellular active compound. In this study, we investigated the effects of estramustine on the binding of MAPs to taxol-stabilized microtubules in vivo. In contrast to previous reports, no effect of estramustine on the binding of MAPs to microtubules was found. Furthermore, we found that polymerization of purified tubulin could be inhibited by estramustine in vitro. Taken together, these results demonstrate that estramustine causes depolymerization of microtubules by direct interaction with tubulin.

Adenocarcinoma↗
PubMed1998

Radionuclide venography in the diagnosis of deep vein thrombosis of the lower extremities: a comparison to contrast venography.

Radionuclide venography (RNV) and contrast venography (CV) were compared in 72 limbs of 59 patients being clinically suspected of deep vein thrombosis (DVT) of the lower extremities. The criteria of positive RNV for DVT regarding flow pattern abnormality included (1) nonfilling or nonvisualization of a deep vein, (2) interruption of the flow, (3) irregular or asymmetric filling of a deep vein, and (4) presence of abnormal collateral vessels. The overall accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR+) were 90 per cent, 88 per cent, 96 per cent, 98 per cent, 79 per cent, and 20.8 respectively. These figures are even higher when we focused on the major veins of the thigh and pelvis. They were 97 per cent, 95 per cent, 98 per cent, 98 per cent, 95 per cent, and 61 respectively. The results indicate that radionuclide venography, while technically simple, is a reliable test for detection of DVT particularly of the major veins of the lower extremities. Combined radionuclide venography and perfusion lung scan can also be performed in the same setting if Tc99m-MAA is used. Contrast venography which is an invasive procedure, should be reserved for questionable cases of those with suspected isolated calf vein thrombosis.

Adolescent↗
PubMed1979

Response of scrotal and non-scrotal vertebrate testis to the male antifertility agent alpha-chlorohydrin.

Effect of single oral dose (90 mg/kg body weight), multiple doses (90 mg/kg body weight for 7 days) or even higher doses (180-300 mg/kg body weight) of alpha-chlorohydrin on the testis-epididymis complex of dog, rat, cryptorchid rat, hedgehog, domestic fowl, lizard, frog, and toad has been studied. alpha-chlorohydrin treatment, at any dose, did not induce lesions in the testis-epididymis complex of dog and hedgehog having testis in scrotum and inguinal canal respectively. Abdominal testis of cryptorchid rat, domestic fowl, lizard, frog and toad also did not respond to alpha-chlorohydrin treatment. Lesions in normal rat testis-epididymis complex, after single oral dose of alpha-chlorohydrin, were quite prominent. Non-sensitivity of alpha-chlorohydrin to these animal species may be due to the absence of the pampiniform plexus complex in hedgehog and sub-mammalian animal species. Absence of conventional epididymis in the sub-mammalian animal species may be the additional reason of the non-sensitivity of the drug. Prominence of collateral blood vasculature in dog testis-epididymis complex and some alterations in the blood supply due to cryptorchidity in cryptorchid rat testis seems to be the reason of non-sensitivity of alpha-chlorohydrin to dog and cryptorchid rat testis. These observations confirm the hypothesis that the action of a single oral dose of alpha-chlorohydrin is associted with the blood vasculature of the testis-epididymis complex.

Animals↗
PubMed1988

Duplex sonography of hepatic artery thrombosis after liver transplantation.

When hepatic artery thrombosis occurs after liver transplantation, another transplantation is required to ensure the patient's survival. Because of the importance of establishing this diagnosis, we reviewed the results of duplex sonography in 37 angiographically or surgically proved cases of hepatic artery thrombosis after liver transplantation. There were 20 children and 17 adults. Ten of the 20 children had angiographically documented hepatopetal arterial collaterals. Such collaterals were not seen in the adult patients. This subset of patients was evaluated separately to determine if intrahepatic arterial blood flow reestablished by collaterals after hepatic artery thrombosis was a cause of false-negative Doppler studies. Thirty-four (92%) of the 37 cases of hepatic artery thrombosis were correctly identified by Doppler. A Doppler pulse was not identified in any of the children with arterial collaterals. We conclude that duplex sonography is sensitive in detecting hepatic artery thrombosis after liver transplantation. Furthermore, the presence of blood flow in hepatopetal arterial collaterals does not cause false-negative examinations.

Adolescent↗
PubMed1990

Magnetic resonance imaging compared with computed tomography and angiography in moyamoya disease.

Magnetic resonance (MR) imaging performed in 13 patients with moyamoya disease was reviewed and compared with computed tomography (CT) and angiography. The MR findings consisted of occlusion of arteries, collateral vessels and parenchymal changes. Narrowing or occlusion of the middle cerebral artery and the supraclinoid portion of the internal carotid artery were seen in all hemispheres but one. Collateral vessels, cerebral infarcts and atrophy with dilatation of the ventricles were observed on MR imaging. In general, the MR findings correlated well with angiography regarding occlusive changes and moyamoya vessels but was less sensitive in a few cases. Because of its higher sensitivity in detecting occlusive changes and collateral vessels, MR imaging was superior to CT in the diagnosis of this disease.

Adolescent↗
PubMed2001

Magnetic resonance angiography of portal collateral pathways after hepatic portoenterostomy in biliary atresia: comparisons with endoscopic findings.

BACKGROUND/PURPOSE: This study was undertaken to assess the usefulness of magnetic resonance angiography (MRA) in detecting varices and to investigate the possibility of avoiding routine endoscopy after surgery for biliary atresia (BA). METHODS: The subjects are 21 patients who have undergone periodical MRA since 1996. The esophageal and gastric vessels were investigated as the sites of potential development of collateral vessels. The collateral vessels on MRA were compared with endoscopic findings. RESULTS: (1) Detection of collateral vessels: of 21 patients examined, 9 patients had 12 varices. MRA depicted collateral vessels in all of the 12 varices (sensitivity, 100%). However, all MRA findings, but one was compatible with endoscopic findings (specificity, 92.9%). Outside of a series of these 21 patients, there were 3 additional patients who had undergone endoscopic treatments previously with success, and in whom esophageal vessels were not depicted on MRA, but endoscopy showed remnant varices. (2) Time-dependent relationship between the appearance of collateral vessels and varices: of 4 varices that appeared after the start of MRA, 3 esophageal varices were found endoscopically simultaneously with or after delineation of collateral vessels on MRA. In the remaining patient, varices were found enodscopically 6 months before the MRA delineation, because a simultaneous MRA was not performed in this case. All these varices were in the early stage. CONCLUSIONS: MRA was highly sensitive and specific in detecting esophagogastric collateral vessels of the portal venous system. An endoscopic examination is unnecessary until collateral vessels are seen on MRA after surgery for BA.

Biliary Atresia↗
PubMed2000

A mean-field model for orientation tuning, contrast saturation, and contextual effects in the primary visual cortex.

Orientation-selective cells in the primary visual cortex of monkeys and cats are often characterized by an orientation-tuning width that is invariant under stimulus contrast. At the same time their contrast response function saturates or even super-saturates for high values of contrast. When two bar stimuli are presented within their classical receptive field, the neuronal response decreases with the intersection angle. When two stimuli are presented inside and outside the classical receptive field, the response of the cell increases with the intersection angle. Both cats and monkeys show iso-orientation suppression, which has sometimes been reported to be combined with cross-orientation facilitation. This property has previously been described as sensitivity to orientation contrast. We address the emergence of these effects with a model that describes the processing of geniculocortical signals through cortical circuitry. We hypothesize that short intracortical fibers mediate the classical receptive field effects, whereas long-range collaterals evoke contextual effects such as sensitivity to orientation contrast. We model this situation by setting up a mean-field description of two neighboring cortical hypercolumns, which can process a nonoverlapping center and a (nonclassical) surround stimulus. Both hypercolumns interact via idealized long-range connections. For an isolated model hypercolumn, we find that either contrast saturation or contrast-invariant orientation tuning emerges, depending on the strength of the lateral excitation. There is no parameter regime, however, where both phenomena emerge simultaneously. In the regime where contrast saturation is found, the model also correctly reproduces suppression due to a second, cross-oriented grid within the classical receptive field. If two model hypercolumns are mutually coupled by long-range connections that are iso-orientation specific, nonclassical surround stimuli show either suppression or facilitation for all surround orientations. Sensitivity to orientation contrast is not observed. This property requires excitatory-to-excitatory long-range couplings that are less orientation specific than those targeting inhibitory neurons.

Animals↗
PubMed1999

Absence of myocardial ischemia during sudden controlled occlusion of coronary arteries in patients with well-developed collateral vessels.

OBJECTIVE: To determine whether the presence of well-developed collateral vessels (visualized by baseline angiography) prevents myocardial ischemia associated with electrocardiographic ST-segment deviation or anginal pain during subsequent coronary balloon occlusion. METHODS: Study patients with stable effort angina but without complete coronary obstruction were divided into two groups on the basis of whether myocardial ischemia was observed during the first minute of coronary balloon occlusion in order to compare the degrees of collateral development at baseline. Patients in group A (n = 47) had electrocardiographic ischemic ST-segment deviations or angina, or both, during balloon inflation, whereas patients in group B (n = 13) had neither. RESULTS: The incidences both of poor anterograde perfusion with TIMI grade 1 or 2 (77 versus 38%, P < 0.05) and of well-developed collateral vessels (Rentrop grade 3) in the perfusion territory of the target vessel for coronary angioplasty (77 versus 15%, P < 0.01) were higher for patients in group B than they were for those in group A. The incidence of no myocardial ischemia during balloon inflation among the patients with well-developed collateral vessels was higher than that among those without (59 versus 7%, P < 0.01). The prediction of the absence of myocardial ischemia during balloon inflation according to whether well-developed collateral vessels were present had the sensitivity 77% (10 of 13) and the specificity 93% (40 of 43) for the study patients. CONCLUSION: Absence of myocardial ischemia (revealed by electrocardiographic changes or angina during transient coronary balloon occlusion) was associated with presence of well-developed collateral vessels (Rentrop grade 3; visualized by baseline angiography), suggesting that the patients with well-developed collateral vessels have a low risk of developing acute myocardial infarction or hemodynamic instability upon abrupt closure of the culprit coronary artery.

Angioplasty, Balloon, Coronary↗
PubMed1999

Recovery of cutaneous pain sensitivity after end-to-side nerve repair in the rat.

OBJECT: The hypothesis that collaterally sprouting axons from an uninjured donor nerve may provide recovery of pain sensitivity in the skin after end-to-side nerve repair was investigated in rats. In addition, the effect of this technique on the donor nerve was examined. METHODS: The distal stump of the transected peroneal nerve was sutured end to side to the intact sural nerve. No epineurial window or perineurial slit was made in the sural nerve at the site of coaptation. Other nerves in the leg were transected and ligated. Eighteen weeks later, the sural nerve was transected at a site distal from the coaptation site. The residual pain sensitivity in the peroneal innervation field in the instep was documented using the skin pinch test in three of 11 animals. The area of sensitivity encompassed 19 to 40% of the maximum nociceptive innervation area of the normal peroneal nerve. The nerve pinch test revealed functional sensory axons in all communicating peroneal nerves, in which 277+/-119 myelinated axons (mean +/- standard deviation) were found by histological investigation. CONCLUSIONS: The authors conclude that at least partial recovery of sensory function due to collateral sprouting of axons after end-to-side nerve repair is possible in principle. However, the presence of functional sensory axons in the peroneal nerve stumps did not guarantee the recovery of skin sensitivity to pain in all animals. No functional or morphological evidence of an untoward effect of collateral sprouting into the end-to-side communicating nerve was detected in the axons of the donor nerve itself.

Animals↗
PubMed1992

Computed tomography in the evaluation of the portal venous system.

Computed tomography has widespread clinical application in the evaluation of the portal venous system, even though quantitative methods are impractical due to the inability to measure portal flow discrete from hepatic arterial flow, morbidity associated with the use of large volumes of iodinated contrast, and technical limitations. This represents a major disadvantage compared to Doppler ultrasound and magnetic resonance angiography. Qualitative applications include evaluation of portal vein patency, diagnosis of portal vein thrombosis, underlying inflammatory or neoplastic conditions, and evaluation of surgically created portosystemic shunts and collateral flow. Diagnostic criteria for portal venous thrombosis include nonopacification of the central portion of the portal vein, peripheral enhancement of the vein, and irregular periportal hepatic parenchymal enhancement. However, misdiagnosis is common, occurring in 16% of cases analyzed in one limited series, and periportal vein enhancement is now recognized as a nonspecific finding associated with underlying endothelial injury. Cavernous transformation of the portal vein and neoplastic invasion of the portal system are more reliably recognized. Computed tomography arterial portography demonstrates collateral pathways and arteriovenous shunts. Computed tomography has a sensitivity of 85% in detection of esophageal varices compared to endoscopy, but has the advantage of demonstrating splenorenal, gastrorenal, peripancreatic, pericholecystic, retroperitoneal and omental collateral vessels, and spontaneous large portosystemic shunts, with greater sensitivity than angiography. Computed tomography combined with Doppler ultrasound angiography remains popular, despite a lack of large-scale prospective efficacy studies demonstrating diagnostic superiority over other imaging techniques, largely because of its accessibility, and its detailed axial anatomic images providing an overview of multiple organ systems, and patency of major vessels.

Collateral Circulation↗
PubMed1998

Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements.

OBJECTIVES: This study evaluated two methods for the quantitative measurement of collaterals using intracoronary (IC) blood flow velocity or pressure measurements. BACKGROUND: The extent of myocardial necrosis after coronary artery occlusion is substantially influenced by the collateral circulation. So far, qualitative methods have been available to assess the human coronary collateral circulation, thus restraining the conclusive investigation of, for example, therapies to promote collateral development. METHODS: Fifty-one patients with a coronary artery stenosis to be treated by percutaneous transluminal coronary angioplasty (PTCA) were investigated using IC PTCA guidewire-based Doppler and pressure sensors positioned distal to the stenosis. Simultaneous measurements of aortic pressure, IC velocity and pressure distal to the stenosis during and after PTCA provided the variables for calculating collateral flow indices (CFIv and CFIp) that express collateral flow as a fraction of flow via the patent vessel. Both CFIv and CFIp were compared with conventional methods for collateral assessment, among them ST-segment changes >1 mm on IC and surface electrocardiogram (ECG) at PTCA. Also, CFIv and CFIp were compared with each other. RESULTS: In 11 patients without ECG signs of ischemia during PTCA (sufficient collaterals), relative collateral flow amounted to 46% as determined by Doppler and pressure wire. Patients with insufficient collaterals (n=40) had relative collateral flow values of 18%. Using a threshold of CFI=30%, sufficient and insufficient collaterals could be diagnosed with 100% sensitivity and 93% specificity by IC Doppler, and 75% sensitivity and 92% specificity by IC pressure measurements. The agreement between Doppler and pressure measurements was good: CFIv=0.08 + 0.8 CFIp, r=0.80, p=0.0001. CONCLUSIONS: Intracoronary flow velocity or pressure measurements during routine PTCA represent an accurate and, at last, quantitative method for assessing the coronary collateral circulation in humans.

Angioplasty, Balloon, Coronary↗
PubMed1996

NMDA-dependent modulation of CA1 local circuit inhibition.

Whole-cell and extracellular recording techniques were used to examine local circuit inhibition in the CA1 region of the rat hippocampus in vitro. Activation, primarily of the recurrent inhibitory circuit by alvear stimulation, elicited an IPSP in pyramidal neurons that was dependent, in part, on NMDA receptor activation. Application of a tetanizing stimulus to the alveus evoked long-term potentiation (LTP) of the intracellularly recorded recurrent IPSPs. This LTP also was NMDA-dependent and was more sensitive to blockade by the NMDA antagonists 2-amino-5-phosphonovalerate (APV) and N-acetyl-aspartyl-glutamate, than the excitatory LTP produced by Schaffer collateral stimulation. With regard to APV, the sensitivity of inhibitory LTP was an order of magnitude greater. A biophysical simulation of hippocampal CA1 circuitry was used in a model of learned pattern recognition that included LTP in both excitatory and inhibitory recurrent circuits. In this model, selective blockade of inhibitory LTP produced aberrant spread of lateral excitation, resulting in confusion of normally distinguishable patterns of neuronal activity. Consideration is given to the possibility that selective disruption of NMDA-dependent modulation of local circuit inhibition may serve as a model for some aspects of dysfunction associated with NMDA-antagonist exposure and schizophrenia.

2-Amino-5-phosphonovalerate↗
PubMed1995

Short- and long-term hemodynamic effects of transjugular intrahepatic portosystemic shunts: a Doppler/manometric correlative study.

OBJECTIVE: The purposes of this study were to evaluate the effect of a well-functioning transjugular intrahepatic portosystemic shunt (TIPS) on the splanchnic and intrahepatic circulation, to determine if sonographic measurements can predict shunt dysfunction before clinical manifestations of portal hypertension occur, and to compare Doppler sonographic findings with portocaval gradient measurements before and after shunt revision. SUBJECTS AND METHODS: Forty-four patients with cirrhosis (n = 43) and myelofibrosis (n = 1) who underwent successful TIPS insertion were included in this prospective study. Indications for TIPS placement were: refractory ascites (24 patients), bleeding esophageal varices (17 patients), portal hypertensive gastropathy (two patients), and bleeding colonic varices (one patient). The portal vein and the inferior vena cava were catheterized; and the portocaval gradient was recorded before TIPS placement, at 2 and 12 months after TIPS placement, and when clinical or Doppler findings suggested shunt dysfunction. Doppler studies were done within 1 week before TIPS placement, within 2 days after TIPS placement, every 2-3 months thereafter, and before and after a TIPS revision. The Doppler studies included flow volume measurements in the portal vein and in the stent, as well as determination of the direction of flow in the segmental branches of the portal vein, in the splanchnic veins, and in portosystemic collaterals. Changes in Doppler findings and in catheter pressure measurements were compared using Spearman's rank correlation test. Significance was set at the .05 level. RESULTS: A marked decrease (-51%) in portocaval gradient was observed after TIPS placement. At Doppler sonography, portal vein velocity and diameter were both higher after TIPS placement, resulting in a marked increase in portal venous flow (170%). Mean flow velocity in the shunt was 55.8 +/- 3.6 cm/sec, and flow volumes in the shunt and in the main portal vein were 1596 ml/min and 1731 ml/min, respectively (p = nonsignificant). Dysfunction of the stent occurred in 27% of the patients. Changes in stent blood flow volume were closely related to changes in the portocaval gradient (r = -0.67, p < .001). Reduction of blood flow volume in the stent or change of direction of flow in intrahepatic portal veins or in collateral veins signaled shunt dysfunction (84% sensitivity, 89% specificity). CONCLUSION: Marked hemodynamic changes in the portal venous system occur soon after a TIPS procedure. Monitoring of shunt function with periodic Doppler sonography, including calculation of shunt blood flow, is useful in detecting shunt dysfunction before clinical signs occur.

Adult↗