Biomedical subjects

L Vachon

Publications and source records attributed to L Vachon.

At least 19 recordsLinked to original sources

PubMed2002

[Potential advantages a new syringe pump system].

OBJECTIVES: To evaluate what could be the benefit in terms of alarm suppression, of a new syringe pumps system, which allows automatic relay without alarms. PATIENTS AND METHODS: We have prospectively recorded the nature and the mode of relay of all syringe pumps for administration of drugs to patients in two ICU. The perfusion regimen was studied in 61 patients over the complete duration of their stay in two ICU. Alarms were also recorded in one ICU room, over 13 days consecutive. The records were processed off-line with an automatic detection-recognition system in order to assess the origin of each alarm. Accordingly, the amount of alarm corresponding to monitor, ventilator and syringe pumps was computed. RESULTS: We found that syringe pumps, which would provide automatic relays without alarm, would suppress 17% of alarms in ICU and automatize 65% of the relay procedures, which are usually performed often in emergency, on response to the end of perfusion alarm. CONCLUSION: New syringe pumps allow both reduction of alarms in ICU and a better management of nurse workload. Indeed syringe relay can be planned in advance.

Equipment Failure↗

PubMed2000

Vigabatrin as add-on therapy for adult complex partial seizures: a double-blind, placebo-controlled multicentre study. The Canadian Vigabatrin Study Group.

Vigabatrin (VGB) is a novel antiepileptic drug effective as adjunctive therapy in patients with partial seizures. In this study, the efficacy and tolerability of VGB as adjunctive therapy were evaluated in patients with refractory epilepsy. Adult patients with a definite diagnosis of complex partial seizures and/or partial seizures secondarily generalized were recruited from 10 Canadian centres. Patients were randomized to receive either active medication or placebo in a double- blind fashion and entered a 36-week titration and maintenance phase with regularly scheduled visits. Both efficacy parameters and safety assessments were monitored. Clinical laboratory, evoked potential studies, MRI, and neuropsychological tests were also performed. Forty-eight percent of VGB-treated patients vs. 26 percent of placebo-treated patients had a 50 percent or greater reduction in the frequency of complex partial seizures and partial seizures secondarily generalized. Vigabatrin was well tolerated by the majority of patients. Minor neurological side effects were observed in a number of patients in both treatment groups. No serious systemic toxicity was observed. No changes in evoked potential studies or MRI findings were noted. Vigabatrin was found to be an effective and well-tolerated antiepileptic drug when used as adjunctive therapy in patients with difficult to control complex partial seizures and for partial seizures secondarily generalized. Vigabatrin is a selective irreversible inhibitor of the GABA- degradating enzyme GABA transaminase and has shown efficacy in a number of clinical trials in patients with difficult to control partial seizures. Vigabatrin has been found most effective against complex partial and secondarily generalized tonic-clonic seizures in both adults and children. Vigabatrin has also been shown to reduce infantile spasms secondary to various aetiologies and is most effective in spasms associated with tuberous sclerosis. The aim of this study was to further extend the clinical experience with VGB as adjunctive therapy in the treatment of adult patients with difficult to control complex partial seizures and/or partial seizures secondarily generalized. In addition to the assessments of efficacy and tolerability to VGB, neuropsychological evaluations were also carried out.

Adolescent↗

PubMed2000

Hydroxyl radical production in the cortex and striatum in a rat model of focal cerebral ischemia.

BACKGROUND: Increases in hydroxyl radical production have been used as evidence of oxidative stress in cerebral ischemia/ reperfusion. Ischemia can also induce increased dopamine release from the striatum that may contribute to hydroxyl radical formation. We have compared hydroxyl radical production in the cortex and striatum as an index of oxidative stress in a rat model of focal cerebral ischemia with cortical infarction. METHODS: Using a three vessel occlusion model of focal cerebral ischemia combined with bilateral microdialysis, hydroxylation of 4-hydroxybenzoate (4HB) was continuously monitored in both hemispheres in either the lateral striatum or frontoparietal cortex. The ischemia protocol consisted of one hour equilibration, 30 min of three vessel occlusion, then release of the contralateral common carotid artery (CCA) for 2.5 h. RESULTS: Induction of ischemia resulted in a 30-fold increase in dopamine release in the lateral striatum. Compared to the nonischemic striatum, the ratio of the hydroxylation product 3,4-dihydroxybenzoate (34DHB) to 4HB (trapping agent) in the ipsilateral striatum increased significantly 30 min after ischemia induction. In contrast, during the 30 min of three vessel occlusion there was no increase in the ratio in the cortex. Following the release of the contralateral CCA, the ratio from the ischemic cortex increased significantly compared to sham-operated animals. However, under all circumstances, the 34DHB/4HB ratio was greater in the striatum than in the cortex. CONCLUSION: The increase in the 34DHB/4HB ratio in the lateral striatum coincides with the increased dopamine release suggesting a role for dopamine oxidation in the increased production of hydroxyl radicals. The significant increase in the ratio from the ischemic cortex compared to that from the sham-operated animals is consistent with increased oxidative stress induced by ischemia. However, the lower 34DHB/4HB ratio in the cortex which does not receive dopaminergic innervation compared to the striatum suggests a different mechanism for hydroxyl radical production. Such an alternate mechanism may represent a more toxic oxidative insult that contributes to infarction.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

[Right atrioventricular metastasis of a myxoid liposarcoma. Case report and al review of the literature].

Malignant tumours of the heart and pericardium are rare. Secondary tumours are 20 to 40 times more common than primary tumours. The authors report the case of a cardiac metastasis of a myxoid liposarcoma of the inguinal region. Surgical ablation with chemotherapy significantly improved the patient' clinical and haemodynamic status. A review of the literature shows that postoperative survival does not exceed 2 years, but the prognosis is better when chemotherapy is associated with surgery. Transoesophageal echocardiography is an excellent diagnostic imaging method. It provides a better evaluation of the tumour and its location, compared to thoracic CT scan and transthoracic echocardiography.

Abdominal Neoplasms↗

PubMed1999

Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.

In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hydroxyl radicals to produce 3,4-dihydroxybenzoate (34DHB), was injected intraperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic contribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either 1-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by high-performance liquid chromatography for catecholamines, 3,4-dihydroxyphenylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical adduct, 34DHB and its precursor, 4HBZ. MPP+ administration resulted in a massive release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+ resulted in a decrease in interstitial 4HBZ to < 50% of the non-MPP+ -treated side. In absolute terms, the amount of 34DHB produced was low but similar in all three groups, even after unilateral MPP+ infusion. When 34DHB was normalized to 4HBZ release to account for differences in precursor availability, there were no significant differences in the 34DHB/4HBZ ratios either with or without MAO inhibitor treatment or after local MPP+ infusion. Systemic 4HBZ administration appears to result predominantly in intra-cellular sampling of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate.

1-Methyl-4-phenylpyridinium↗

PubMed1999

Life expectancy and causes of death in a population treated for serious mental illness.

OBJECTIVE: This cross-sectional mortality linkage study describes the prevalence of specific fatal disease and injury conditions in an adult population with serious mental illness. The large sample of decedents and the use of multiple-cause-of-death data yield new clinical details relevant to those caring for persons with serious mental illness. METHODS: Age-adjusted frequency distributions and years of potential life lost were calculated by gender and causes of death for persons in the population of 43,274 adults served by the Massachusetts Department of Mental Health who died between 1989 and 1994. Means and frequencies of these variables were compared with those for persons in the general population of the state who did not receive departmental services and who died during the same period. RESULTS: A total of 1,890 adult decedents served by the department of mental health were identified by electronic linkage of patient and state vital records. They had a significantly higher frequency of deaths from accidental and intentional injuries, particularly poisoning by psychotropic medications. Deaths from cancer, diabetes, and circulatory disorders were significantly less frequently reported. On average, decedents who had been served by the department of mental health lost 8.8 more years of potential life than decedents in the general population-a mean of 14.1 years for men and 5.7 for women. The differential was consistent across most causes of death. CONCLUSIONS: Findings in this study are consistent with previous findings identifying excess mortality in a population with serious mental illness. The high rate of injury deaths, especially those due to psychotropic and other medications, should concern providers.

Adolescent↗

PubMed1996

Evaluation of sodium 4-hydroxybenzoate as an hydroxyl radical trap using gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection.

Molecular and tissue damage induced by reactive oxygen species is a serious consequence of the production of free radicals in biological systems. Biological markers produced by reactions with hydroxyl radicals are useful indices of free radical processes in vivo. In this respect, hydroxylation of aromatic compounds such as salicylate (2-hydroxybenzoate) has been used extensively as a measure of hydroxyl radical formation. 4-Hydroxybenzoate will also trap hydroxyl radicals with fewer of the complications for which salicylate has been criticized. We describe two sensitive and specific methods using gas chromatography-ion trap mass spectrometry and high-performance liquid chromatography with electrochemical detection for a number of these aromatic marker compounds in biological fluids. The use of an ion trap mass spectrometer provides enhanced sensitivity along with full mass spectral identification of the compounds of interest. 4-Hydroxybenzoate and salicylate were compared as hydroxyl radical traps (i) by determining relative hydroxyl radical trapping efficiencies in vitro, (ii) by measuring individual dihydroxybenzoate isomers in rat serum following intraperitoneal injection of either 2- or 4-hydroxybenzoate, and (iii) by comparing in vivo hydroxyl radical trapping using intrastriatal microdialysis in the rat. The techniques described have broad applications in the area of free radical biomedical research.

Animals↗

PubMed1996

In vivo hydroxylation of the neurotoxin, 1-methyl-4-phenylpyridinium, and the effect of monoamine oxidase inhibitors: electrospray-MS analysis of intra-striatal microdialysates.

The neurotoxin 1-methyl-4-phenylpyridinium (MPP+) has been shown to increase hydroxyl radical formation in the striatum. The production of hydroxyl radicals correlates with the MPP(+)-driven dopamine release which presumably leads to increased metabolism via monoamine oxidase or increased dopamine autoxidation. Both processes result in enhanced production of hydrogen peroxide, which in the presence of iron(II) ions decomposes to the hydroxyl radical. Monoamine oxidase inhibitors decrease the production of hydroxyl radicals as measured by salicylate and 4-hydroxybenzoate trapping. As both MPP+ and monoamine oxidase inhibitors, such as deprenyl and MDL-72,974A, possess aromatic rings, hydroxyl radical adduct formation was investigated in vitro in defined Fenton systems and also in vivo using intra-striatal microdialysis to infuse MPP+ to rats pretreated systemically with either deprenyl or MDL-72,974A. Electrospray mass spectrometric analysis, using full-scan, fragment ion and constant neutral loss spectra, demonstrated ring hydroxylation of all three compounds in the Fenton systems. Spectral comparison of microdialysis samples with spectra from the Fenton reactions indicated the in vivo hydroxyl radical adduct attachment to MPP+, deprenyl and possibly MDL-72,974A.

1-Methyl-4-phenylpyridinium↗

PubMed1995

Hydroxylation of aromatic compounds as indices of hydroxyl radical production: a cautionary note revisited.

While setting up an intracerebral microdialysis system to estimate the extent of oxidative stress induced by the neurotoxin, N-methylphenylpyridinium ion (MPP+), we encountered a problem in the use of hydroxybenzoic acids as traps of hydroxyl radicals. Using either 2-hydroxybenzoate (salicylate) or 4-hydroxybenzoate as trapping agents, we observed a nonspecific, that is, nontissue derived, production of hydroxyl radicals as measured by the hydroxylation products, 2,3- and 2,5-dihydroxybenzoate from 2-hydroxybenzoate and 3,4-dihydroxybenzoate from 4-hydroxybenzoate. This production of dihydroxybenzoates was 10 times that expected due to the administration of MPP+, thus making it impossible to interpret our results. Careful investigation of the various components of the microdialysis system indicated that contact of the microdialysate with metal surfaces resulted in dihydroxybenzoic acid formation. These results should serve as a reminder to perform stringent tests of the experimental system prior to experiments with biological tissues to evaluate the contribution of hydroxyl radical production from nonbiological sources. Therefore, along with the possibility of enzymatic production of dihydroxybenzoates, artefactual production by components of the experimental apparatus must be considered before assuming that one is measuring hydroxyl radical production by a biological system.

1-Methyl-4-phenylpyridinium↗

PubMed1995

Dose frequency and dose interval compliance with multiple antiepileptic medications during a controlled clinical trial.

Compliance with medication regimens and clinical trial schedules was evaluated during a study of vigabatrin (VGB), an antiepileptic drug (AED). Medication Event Monitors (MEMS, Aprex Corp., Fremont, CA, U.S.A.) were provided to monitor use of VGB and other AEDs administered to 111 patients at 10 sites. MEMS reports showed the number of doses administered daily, times of doses, and intervals between doses. The 66 patients whose data were evaluable took VGB as prescribed (twice daily, b.i.d.) on 89 +/- 7% of days in the clinical trial (mean 189 +/- 63 days). However, only 66 +/- 24% of doses were taken within the 9-15-h dose interval window for twice-daily dosing, a lower rate than that for dose frequency compliance (p < 0.001). Concomitant medications prescribed b.i.d. (n = 66) (86 +/- 11% dose frequency compliance) were taken at lower rates than VGB (p < 0.02). Interval compliance also was lower for concomitant b.i.d. medications (59 +/- 26%) than for VGB (p < 0.01). Dose frequency compliance for thrice-daily (t.i.d.) medications (n = 36) was 80 +/- 18 and 40 +/- 19% for interval compliance (6-10 h) (both p < 0.0001 vs. VGB). Dose frequency compliance for four times daily (q.i.d.) medications (n = 23) was 80 +/- 23 and 33 +/- 18% for interval compliance (4-8 h) (both p < 0.0001 vs. VGB). Patients at eight sites did not use MEMS properly, often for practical reasons, voiding including of data for 93 medications (32%) because of noncompliance with the study design to monitor compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes.

To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range, 91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2; range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group (379 mL/1.73 m2; range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range, 347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

Adult↗

PubMed1991

Bromocriptine in the treatment of alcohol dependence.

A double-blind controlled study of the effects of bromocriptine on drinking behavior and associated symptoms in ambulatory alcoholics showed a marked improvement in both treatment and control groups. However, significant differences in favor of the medication were observed in psychopathological measures, and trends in the same direction in most of the other efficacy parameters.

Adult↗

PubMed1990

CQA 206-291 in Parkinson's disease: an acute single escalating dosage study.

CQA 206-291, a new ergot derivative with a "biphasic" dopaminergic profile, was studied in 6 patients with longstanding Parkinson's disease suffering from pronounced fluctuations in hourly mobility. On alternate days, up to seven single doses, escalating from 0.2 to 20 mg, were given as replacement for the usual first morning dose of levodopa. At the most effective dosage, four of the six patients obtained as good a peak response to CQA (8-20 mg) as to L-dopa. Side effects were common and similar to other ergot derivatives, suggesting that the initial weak dopamine antagonist properties of the parent compound, documented in animals, may be of little clinical significance. However, comparative studies will be needed to confirm this suspicion. The addition of domperidone successfully reduced the incidence and severity of side effects. CQA 206-291 has potent anti-parkinsonian properties; further longer-term treatment trials are indicated.

Aged↗

PubMed1990

Long term treatment with CV 205-502 in patients with prolactin-secreting pituitary macroadenomas.

CV 205-502, a new long-acting nonergot dopamine agonist, was given to 15 patients (6 women and 9 men) with PRL-secreting pituitary macroadenomas. The compound was administered in a single daily dose for a period of 6-12 months. The treatment resulted in normalization of plasma PRL levels (less than or equal to 20 micrograms/L) in 5 of 6 women at a mean dose of 135 micrograms (range, 75-300 micrograms) and in 6 of 9 men at a mean dose of 192 micrograms (range, 75-300 micrograms). Among patients for whom computed tomographic scans were available before and after at least 6 months of therapy, definite tumor shrinkage occurred in 6 of 7 patients. Libido was improved in 5 of 6 women and in 6 of 8 men, galactorrhea disappeared in all cases (3 women and 1 man) and menses resumed in 3 of 5 women. Plasma testosterone rose to normal levels in 3 of 6 men who were not receiving testosterone injections. The PRL response to TRH was blunted in 4 of 6 patients with normalized basal PRL. Serum total cholesterol was reduced by CV 205-502 treatment in women from 5.35 +/- 0.49 to 4.63 +/- 0.51 mmol/L (P = 0.031) and in men from 5.93 +/- 0.89 to 5.28 +/- 0.82 mmol/L (P = 0.045). Side-effects included mainly headache, nausea, and dizziness. One side-effect or more occurred transiently and with mild intensity in 14 patients. No patient discontinued the therapy because of side-effects. In conclusion, CV 205-502 appears to be a safe and valuable compound in the treatment of patients with PRL-secreting macroadenomas.

Adult↗

PubMed1990

Acrocephalospondylosyndactyly--a possible new syndrome: analysis of the vertebral and intervertebral components.

Apert-Crouzon syndrome (formerly ACS type 2; 10130) is now considered a subset of autosomal dominant Apert acrocephalosyndactyly type 1 (10120), with features of craniosynostoisis, syndactyly of all extremities, maxillary hypoplasia, "parrot-beaked" nose, hypertelorism, exophthalmos, external strabismus, and short upper lip. We report a 3 1/2-month-old infant with features of Apert syndrome, plus thoracic vertebral anomalies radiographically similar to those seen in spondylothoracic dysplasia, a condition in which block thoracic vertebrae with widely open neural arches and a fan-shaped thoracic cage are found. Our patient also had flared metaphyseal ends of humeri, dislocated radii with immobile elbows, an unusual tail-like protuberance in the coccygeal area, and a solid cartilaginous tracheal wall. To date, in ongoing reviews of radiographs of other patients with acrocephalosyndactyly or acrocephalopolysyndactyly complexes and of relevant literature, we have not identified other patients with these findings. The vertebrae and intervertebral discs of the patient in this report, three patients with Jarcho-Levin syndrome, and one with Apert syndrome were measured from anteroposterior chest radiographs; the findings clearly distinguish the condition in our patient from Jarcho-Levin syndrome or Apert syndrome.

Abnormalities, Multiple↗

PubMed1989

Ultrasound finding of peripelvic urine extravasation in ureteropelvic junction obstruction.

Pylosinus backflow is usually associated with acute obstruction and occurs as the result of increased hydrostatic pressure in the renal pelvis. Microruptures or tears occur at the calyceal fornix. The extravasating urine may then be absorbed by lymphatics, rupture into veins, or dissect in the renal sinus. As extravasating urine extends from the peripelvic tissues into the perirenal space, it becomes easily visualized by ultrasound as a perirenal fluid collection. We describe the ultrasound finding of decreased peripelvic echogenicity in an infant with ureteropelvic junction obstruction and peripelvic urine extravasation. To our knowledge this finding on ultrasound has not been previously described. If not for the peripelvic decreased echogenicity, the resulting pelvic decompression may have otherwise mimicked a nonobstructed kidney.

Humans↗

PubMed1988

Opioid receptors are coupled tightly to G proteins but loosely to adenylate cyclase in NG108-15 cell membranes.

Opioid receptors in intact NG 108-15 cells were irreversibly inactivated with increasing concentrations of the alkylating antagonist beta-chlornaltrexamine (CNA). The consequence of the reduction in density of opioid binding sites (quantified by saturation analysis of opioid binding in membranes) was studied at two steps of opioid receptor-mediated responses, (a) stimulation of high affinity GTPase and (b) inhibition of basal adenylate cyclase. Both agonist-mediated stimulation of GTPase and inhibition of adenylate cyclase activities were progressively reduced as the concentration of CNA in the pretreatment was increased. However, the loss of responsiveness for the two enzymes differed in two aspects. First, the diminution of GTPase responsiveness was in agreement with the loss of binding sites and took place at concentrations of CNA that were lower than those necessary to reduce responsiveness of adenylate cyclase. Second, the loss of responsiveness of GTPase occurred simply as reduction of maximal stimulation, whereas that of adenylate cyclase involved an initial reduction of apparent agonist affinity (10-fold) that was followed by a decrease in maximal effect. We next examined the loss of responsiveness of both GTPase and adenylate cyclase in membranes prepared from cells that had been exposed to increasing concentrations of pertussis toxin (PTX) to inactivate PTX-sensitive G proteins in vivo. Also in this case, the extent of reduction in responsiveness was more pronounced for GTPase than for adenylate cyclase, especially in membranes treated with high concentrations of PTX. However, the pattern of loss was identical for the two enzymes and involved a main reduction in maximal effect of the agonist that was followed only after a large degree of inactivation (greater than 60%) by a diminished apparent affinity for the agonist. Opioid receptor-mediated inhibition of cAMP accumulation in intact cells exhibits an IC50 for the agonist that is 30-10 times lower than that measured in membranes for stimulation of GTPase or inhibition of cyclase, respectively. Treatment of cells with either CNA (1 microM) or various concentrations of PTX altered the concentration-response curves for agonist-mediated inhibition of cAMP accumulation in a manner similar to that observed for adenylate cyclase in membranes, inasmuch as both maximal inhibition and apparent affinities for the agonist were decreased. However, this decrease in affinity (5-fold) was not sufficient to eliminate the discrepancy in agonist potency between membranes and intact cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate Ribose↗

PubMed1987

Opioid receptor desensitization in NG 108-15 cells. Differential effects of a full and a partial agonist on the opioid-dependent GTPase.

Opioid-receptor binding and the opioid-mediated stimulation of low Km GTPase and inhibition of adenylate cyclase were studied in membranes derived from NG 108-15 cells pretreated with either the opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) or morphine. Pretreatment with DADLE resulted in a concentration-dependent loss of responsiveness of GTPase to the peptide; this effect was entirely accounted for by a reduction in the maximal stimulation produced acutely by DADLE, without changes in the EC50 of the peptide, indicating a non-competitive type of desensitization. The degree of desensitization of GTPase was similar after one and 24 hr of pretreatment with DADLE, indicating that the process occurs rapidly. In contrast, morphine, which was 70-80% as potent as DADLE in stimulating GTPase and inhibiting adenylate cyclase in acute conditions, induced only a minimal desensitization of the opioid-GTPase system and, in contrast to DADLE, did not desensitize adenylate cyclase. Pretreatment with DADLE for one hour led to a decrease in opioid receptor density which was quantitatively similar to the degree of desensitization of GTPase: both these effects of DADLE were antagonized to a similar extent when morphine was also present in the pretreatment. Thus, desensitization of the opioid-stimulated GTPase appears to be correlated with down-regulation of the opioid receptor. Moreover, these findings suggest that partial agonists cannot induce this process.

Adenylyl Cyclase Inhibitors↗