Dopamine D1 receptors labelled with [3H]SCH23390 in rabbit cerebral cortex and neostriatum. Equilibrium binding, kinetics and selectivity.

The binding characteristics of the novel benzazepine compound SCH23390 were studied using membrane preparations from rabbit cerebral cortex (CTX) and neostriatum (CPU; caudate putamen). The association kinetics of [3H]SCH23390 to membranes from CTX and CPU were rapid, while the dissociation kinetics were extremely slow and only around 40-60% of the binding was displaced two hours after the addition of either S(+)-butaclamol or 30 volumes of buffer. The saturation curves revealed that [3H]SCH23390 bound with high affinity in both tissues, with densities of 133 fmol/mg protein for CTX (Kd 25 degrees C = 0.31 nM) and 664 fmol/mg protein for CPU (Kd = 0.13 nM). the specificity of binding to the cortical D1 receptor was verified in competition experiments with a variety of dopaminergic agents. The rank order of potency of these compounds was consistent with the pharmacology of the dopaminergic D1 site. All competition curves were better fitted to a one-site model with Hill coefficients around one, indicating that [3H]SCH23390 was binding to a single cortical site. The stereoselectivity of the cortical [3H]SCH23390 binding site could be demonstrated by the use of enantiomer pairs of dopaminergic drugs. This study provides compelling evidence that [3H]SCH23390 binds to dopamine D1 receptors in the neostriatum and cerebral cortex of the rabbit.

[Dilatation enteroplasty for obstructive Crohn disease. Experience of the University of Montreal]. / L'entéroplastie d'élargissement pour maladie de Crohn obstructive. Expérience de l'Université de Montréal.

Multiple small bowel resections for obstructive symptoms caused by Crohn's disease can lead to a short bowel and malabsorption. Preservation of intestinal length is possible by the use of strictureplasty. Between August 1983 and March 1993, ninety strictureplasties were performed in 25 patients. They were 13 males and 12 females with a mean age of 37 years. Fourteen (56%) previously had small bowel resection for Crohn's disease. A mean number of 4.3 strictureplasties per patient were performed. Concomitant resection of bowel with active disease was performed in 18 patients (72%). In this series, no perioperative death occurred and one patient developed an enterocutaneous fistula. The overall complication rate was 8%. Postoperatively, 18 patients (72%) were completely relieved of symptoms, 6 were improved (24%) and one became worst (4%). After a 27 month follow-up period, the symptoms recurred in 13 patients (52%); three had no treatment, 7 had medical treatment and 3 required reoperation (12%). Our results support the safety and the use of strictureplasty for stenotic bowel lesions associated with Crohn's disease.

Acute effects of lithium on dopaminergic responses: iontophoretic studies in the rat visual cortex.

The interactions between lithium and cortical dopaminergic receptors were investigated using the iontophoretic technique to record and apply dopaminergic compounds, GABA, acetylcholine and LiCl on neurons in the primary visual cortex of the rat. The main responses to dopamine (DA) or to the D1 agonist (+/- )SKF38393 on spontaneously-active (SA) or visually-driven (VD) units was a prolonged decrease in firing and a reduction in the responsiveness to pulses of acetylcholine. The D1 antagonist SCH23390, applied iontophoretically or intravenously, blocked or attenuated the inhibitory responses to both DA and (+/- )SKF38393. The D2 agonist quinpirole (LY171555) either produced only slight excitations or had no effects on both VD and SA units. The concomitant application of lithium blocked the inhibitory responses to DA and to (+/- )SKF38393 but did not modify the responsiveness to LY171555. In addition, the DA- and (+/- )SKF38393-induced decreases in responsiveness to acetylcholine were also suppressed by lithium. These effects were on dopaminergic mechanisms, since the excitatory responses to acetylcholine alone as well as the inhibitions caused by GABA were unchanged by the application of lithium. These results imply that the modifications in sensitivity to dopaminergic agents induced by lithium are mediated by dopamine D1 receptors and are discussed in relation to adenylate-cyclase.

Effects of sodium, lithium, and magnesium on in vitro binding of [3H]SCH23390 in rat neostriatum and cerebral cortex.

The effects of sodium, lithium, and magnesium on the in vitro binding properties of the D1 antagonist [3H]SCH23390 were examined with membrane preparations from rat neostriatum (CPU; caudate-putamen) and cerebral cortex (CTX). The saturation binding isotherms for both tissues performed in the presence of 120 mM of either Na+ or Li+ revealed an increase in the affinity, as compared to that observed when the incubation buffer was composed of Tris-Cl 50 mM with MgCl2 1 mM alone. For the CPU there were no changes in the maximum binding capacity (Bmax) in the different buffers used. In the case of the CTX, there was a loss of [3H]SCH23390 binding sites when either Na+ or Li+ 120 mM were added to the incubations, suggesting a lack of selectivity of this ligand in the absence of group IA cations. The agonist state of the [3H]SCH23390 binding site was studied in competition experiments with dopamine. The highest agonist affinity was obtained in 50 mM Tris-Cl buffer with 1 mM MgCl2 while the addition of 120 mM of either Na+ or Li+ caused a 3- to 5-fold decrease in the potency of dopamine to compete with specific [3H]SCH23390 binding in both CPU and CTX. The presence of magnesium was essential for the competition experiments; i.e.: a concentration of 1 mM MgCl2 was optimum to obtain dopamine antagonism of ligand binding, while increasing Mg2+ to 2 or 5 mM did not appear to further improve the inhibitions. The results support both agonist and antagonist affinity shifts for the dopamine D1 receptor labeled with [3H]SCH23390.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine D2 receptors labeled with [3H]raclopride in rat and rabbit brains. Equilibrium binding, kinetics, distribution and selectivity.

The binding properties of the substituted benzamide raclopride to dopamine D2 receptors were studied with membrane preparations from rat and rabbit neostriatum. An analysis of the association kinetics suggested a single binding site but the data from the dissociation experiments were better described by a two-site model. Examination of saturation curves at equilibrium revealed a single class of binding sites in the neostriatum from both species (rat: maximum binding capacity (Bmax) = 247 fmol/mg of protein; rabbit: Bmax = 337 fmol/mg of protein). In cortical regions known to possess a distinct dopaminergic innervation (piriform-entorhinal areas and cingulate cortex) the Bmax values ranged between 9 and 22 fmol/mg of protein. [3H]Raclopride binding sites (less than 12 fmol/mg of protein) were also detectable in the dorsal and ventral hippocampus as well as in the somatosensory and visual cortices. The selectivity in the neostriatum was examined by competition experiments with dopaminergic drugs. The rank of potency of agonists and antagonists to displace [3H]raclopride binding revealed its selectivity for the dopamine D2 receptor and was essentially the same for both species. Antagonist competition curves could be fitted to a single site but inhibition by agonists was better described assuming a two-site model. The stereospecificity of binding was demonstrated by the use of the enantiomer pairs. These results validate the utilization of the novel benzamide [3H]raclopride as a selective marker of dopamine D2 receptors.

Treatment of femoral artery pseudoaneurysms with percutaneous thrombin injection.

The objective of this study was to prospectively evaluate the efficacy of ultrasound-guided thrombin injection for the treatment of post-catheterization femoral artery pseudoaneurysms. Between August 1, 1998 and August 31, 1999, 38 patients underwent ultrasound-guided injection of thrombin into 39 femoral false aneurysms. Peripheral pulses and ankle/brachial indices were assessed before and after the injection. Patients were followed with a control duplex scan within 4 weeks. The good results from this study showed that ultrasound-guided thrombin injection is an effective method for the treatment of post-catheterization false aneurysms. In a minority of patients, signs consistent with arterial embolization or vasospasm were identified.

Early vascular complications after endovascular repair of aortoiliac aneurysms.

The purpose of this study was to estimate the frequency of and review the treatment options for intraoperative endograft access-related vascular complications and early postoperative vascular complications of endovascular repair for aortoiliac aneuryms (EVAR). Between February 1998 and April 2000, 53 patients (46 males, 7 females) with aneurysms of the abdominal aorta (AAA) and iliac arteries were treated with endovascular grafts (48 AAA, and 5 iliac aneurysms). All procedures were performed using open exposure of the femoral arteries. One patient with an AAA was converted to open repair (primary technical success, 98.1%). We recorded the need for adjunctive vascular procedures or intervention to the access arteries (iliofemoral) or the endograft because of thrombosis or distal embolization. Events were classified as either intraoperative, early postoperative (< 30 postoperative days), or late postoperative. Their etiology and treatment were recorded. The results were compared to those from other series reported in the literature and to published registry data. From our results we concluded that the need for adjunctive vascular procedures to the iliofemoral arteries at the time of EVAR is significant. These procedures are necessary to either repair damage to the access arteries from the delivery system or provide a conduit for graft delivery in cases where the access arteries are inadequate. Early postoperative vascular complications are due to technical factors resulting in residual graft limb stenoses. Both intraoperative and early postoperative vascular complications after EVAR are more common in female patients. These complications can be effectively treated with a variety of open surgical and transfemoral endovascular techniques.