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1.
Wien Med Wochenschr ; 156(9-10): 241-4, 2006 May.
Article in German | MEDLINE | ID: mdl-16830239

ABSTRACT

Therapy and the handling of dyspnea in the last period of one's life is described and discussed from a case report. A patient with lung cancer and a distinct chronic obstructive pulmonary disease is presented. His coping with increasing dyspnea and the therapeutic strategies are described. Problems with the side effects of therapy and coping strategies are dealt with, too.


Subject(s)
Dyspnea/therapy , Palliative Care , Terminal Care , Adaptation, Psychological , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/psychology , Carcinoma, Squamous Cell/therapy , Disease Progression , Dose-Response Relationship, Drug , Drug Combinations , Dyspnea/etiology , Dyspnea/psychology , Humans , Lung Neoplasms/complications , Lung Neoplasms/psychology , Lung Neoplasms/therapy , Male , Middle Aged , Morphine Derivatives/administration & dosage , Nalorphine/administration & dosage , Nalorphine/analogs & derivatives , Palliative Care/psychology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/psychology , Pulmonary Disease, Chronic Obstructive/therapy , Sick Role , Terminal Care/psychology
2.
Wien Med Wochenschr ; 156(9-10): 275-82, 2006 May.
Article in German | MEDLINE | ID: mdl-16830246

ABSTRACT

On the basis of a case study, the complex problems of the final stages of a COPD will be demonstrated and discussed. Dyspnea and anxiousness are the primary symptoms. If they can be adequately brought under control by opiates and benzodiazepines, a palliative sedation is then not necessary. The communicative and ethical demands on the team responsible are high. It is important to be aware of the specific needs of the patient and of his/her family members, and to competently accompany the patient throughout the decision-making process--such as the decision to end respiratory therapy, for example. Clarifying the situation with the patient and finding out his/her wishes, accompanied by the corresponding documentation, is advisable.


Subject(s)
Ethics, Medical , Palliative Care/ethics , Pulmonary Disease, Chronic Obstructive/therapy , Terminal Care/ethics , Aged , Anxiety/drug therapy , Anxiety/psychology , Conscious Sedation/ethics , Continuous Positive Airway Pressure/ethics , Continuous Positive Airway Pressure/psychology , Drug Combinations , Humans , Male , Medical Futility/ethics , Medical Futility/psychology , Morphine/administration & dosage , Morphine Derivatives/administration & dosage , Nalorphine/administration & dosage , Nalorphine/analogs & derivatives , Pain/drug therapy , Pain/psychology , Palliative Care/psychology , Pulmonary Disease, Chronic Obstructive/psychology , Terminal Care/psychology , Treatment Refusal/ethics , Treatment Refusal/psychology
3.
Pharmacol Biochem Behav ; 63(3): 481-8, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10418791

ABSTRACT

Rats trained to discriminate the mu agonists fentanyl or morphine from their respective vehicles generalize to the partial mu agonist nalorphine incompletely and inconsistently. Any number of factors may influence the generalization patterns obtained, one of which being the specific dose of the full opioid agonist used during training, a factor reported to influence generalization with other partial opioid agonists. To assess if training dose influences stimulus generalization to nalorphine and to support its role in the aforementioned variability across studies, in the present experiments rats were trained to discriminate either a low (5.6 mg/kg) or a high (10 mg/kg) dose of morphine from distilled water within the taste aversion baseline of drug discrimination learning. Subjects were then given a range of doses of morphine, nalorphine, methadone, or naloxone to assess the degree of substitution (if any) of these compounds for the training dose of morphine. For all subjects, morphine fully substituted for itself, and the opioid antagonist naloxone failed to substitute for the morphine cue. Rats generalized the morphine cue to nalorphine in subjects trained at the lower dose but not in subjects trained at the higher dose. Rats generalized the morphine cue to methadone in the latter group (the high dose group), indicating that the failure to generalize to nalorphine in this group was not a general inability of an opioid agonist to substitute for morphine. Naloxone blocked morphine stimulus control in all subjects and nalorphine control in the low-dose group for which nalorphine substituted for morphine, suggesting that morphine control (and the nalorphine substitution) was based on opioid activity. These results indicate that the substitution patterns of nalorphine in morphine-trained subjects are a function in part of the dose of morphine used in training and support the position that nalorphine is a partial opioid agonist with intermediate efficacy.


Subject(s)
Discrimination Learning/drug effects , Discrimination, Psychological/drug effects , Morphine/pharmacology , Nalorphine/pharmacology , Narcotic Antagonists/pharmacology , Narcotics/pharmacology , Animals , Dose-Response Relationship, Drug , Drinking/drug effects , Female , Generalization, Response/drug effects , Methadone/administration & dosage , Methadone/pharmacology , Morphine/administration & dosage , Nalorphine/administration & dosage , Narcotic Antagonists/administration & dosage , Narcotics/administration & dosage , Rats , Rats, Long-Evans
4.
Eksp Klin Farmakol ; 61(1): 25-9, 1998.
Article in Russian | MEDLINE | ID: mdl-9575407

ABSTRACT

Experiments on 81 rabbits showed that intravenous infusion of naloxone and nalorphine in different periods of hemorrhagic shock promoted the death of animals. It is concluded that in hypoxia only the antagonistic activity of the drugs is manifested as total inactivation of the endogenous opioid system depriving it of its protective functions. Nalorphine infused after blood reinfusion exhibits agonistic activity and additional activation of the endogenous opioid system promotes the use of the biological reserves by the organism, which saves some of the animals from death or essentially prolongs the survival of the others. Infusion of naloxone after blood transfusion has no effect on the outcome.


Subject(s)
Nalorphine/pharmacology , Naloxone/pharmacology , Narcotic Antagonists , Narcotic Antagonists/pharmacology , Shock, Hemorrhagic/drug therapy , Acute Disease , Animals , Blood Transfusion, Autologous , Combined Modality Therapy , Drug Evaluation, Preclinical , Hemodynamics/drug effects , Nalorphine/administration & dosage , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Rabbits , Receptors, Opioid/agonists , Receptors, Opioid/drug effects , Shock, Hemorrhagic/mortality , Shock, Hemorrhagic/physiopathology , Time Factors
5.
Eur J Pharmacol ; 272(1): 111-4, 1995 Jan 05.
Article in English | MEDLINE | ID: mdl-7713142

ABSTRACT

Analgesic cross-tolerance between alpha 2-adrenoceptor and opioid receptor agonists was studied using the mouse tail-flick assay. Mice tolerant to clonidine (0.3 mg/kg s.c.) or xylazine (7 mg/kg s.c.) were cross-tolerant to morphine (5 mg/kg s.c.), nalorphine (70 mg/kg s.c.) and supraspinal [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 4 ng i.c.v.), but not trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl] benzeneacetamide methanesulfonate (U50,488; 5 mg/kg s.c.), spinal DAMGO (10 ng i.t.), supraspinal [D-Pen2,D-Pen5]enkephalin (DPDPE; 9 micrograms i.c.v.) or spinal DPDPE (700 ng i.t.). In the complimentary studies, mice tolerant to morphine and nalorphine were cross-tolerant to both of the alpha 2-adrenoceptor agonists, but U50,488 tolerant mice were not. The results suggest differential interactions between alpha 2-adrenoceptor and mu 1-, mu 2-, delta-, kappa 1- and kappa 3-opioid analgesic circuitry.


Subject(s)
Adrenergic alpha-Agonists/pharmacology , Analgesics/pharmacology , Receptors, Opioid/agonists , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer , Adrenergic alpha-Agonists/administration & dosage , Analgesics/administration & dosage , Animals , Binding Sites , Clonidine/administration & dosage , Clonidine/metabolism , Clonidine/pharmacology , Drug Tolerance , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Enkephalin, D-Penicillamine (2,5)- , Enkephalins/administration & dosage , Enkephalins/pharmacology , Injections, Intraventricular , Injections, Subcutaneous , Male , Mice , Morphine/administration & dosage , Morphine/metabolism , Morphine/pharmacology , Nalorphine/administration & dosage , Nalorphine/metabolism , Nalorphine/pharmacology , Narcotic Antagonists , Pyrrolidines/administration & dosage , Pyrrolidines/pharmacology , Receptors, Opioid, delta/agonists , Receptors, Opioid, kappa/antagonists & inhibitors , Receptors, Opioid, mu/agonists , Xylazine/administration & dosage , Xylazine/pharmacology
7.
Farmakol Toksikol ; 53(2): 64-6, 1990.
Article in Russian | MEDLINE | ID: mdl-2369960

ABSTRACT

Acute experiments on 86 adult rabbits have shown that in the early period of Cannon's traumatic shock nalophine and naloxone relieve torpidity, restore motor activity and responses to standard stimuli. This prolongs the animal life (nalorphine) and increases the survivability (naloxone). However in some rabbits a premature relief of torpidity (0.5 mg/kg of nalorphine) precipitates the animal death. It is concluded that in the late period the drugs exert no effect on the shock outcome and that inactivation of opioid suppression system can either trigger the mechanism of shock withdrawal or promote a reduction of its severity.


Subject(s)
Narcotic Antagonists/therapeutic use , Shock, Traumatic/drug therapy , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Nalorphine/administration & dosage , Naloxone/administration & dosage , Rabbits , Shock, Traumatic/mortality , Shock, Traumatic/physiopathology , Time Factors
8.
Ortop Travmatol Protez ; (11): 28-31, 1989 Nov.
Article in Russian | MEDLINE | ID: mdl-2630980

ABSTRACT

In their acute experiments on 86 rabbits the authors have established that the intravenous administration of nalorphine and naloxone produces a marked therapeutic effect only during the early period of experimental traumatic shock. In most of the animals there was a reliable extension of the lifetime (nalorphine) and an increase in the survival rate (naloxone). In a lesser part of the animals the administration of nalorphine had no considerable influence on the outcomes. During the late period the therapeutic effect of these drugs has not yet been manifested. A conclusion has been made that the contradictory data in the literature concerning the effect of nalorphine and naloxone on the course of experimental traumatic shock seem to depend on the fact that they were administered at various stages of this pathologic process. It is pointed out that it is advisable to administer these drugs (especially naloxone) at the pre-hospital stage in the patients with traumatic shock.


Subject(s)
Nalorphine/administration & dosage , Naloxone/administration & dosage , Shock, Traumatic/drug therapy , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Rabbits , Time Factors
9.
Life Sci ; 45(8): 671-8, 1989.
Article in English | MEDLINE | ID: mdl-2779356

ABSTRACT

A sensitive taste conditioning test was used to measure the aversive effect of a single intraventricular (i.c.v.) or subcutaneous (s.c) injection of an opioid antagonist that readily crosses the blood brain barrier (naltrexone), and one of two that do not (methylnaltrexone and diallylnormorphinium). This was done in drug-naive rats and in rats implanted 5 days earlier with a pellet containing 75 mg morphine. It was found that the morphine exposure had no significant effect on the dose-response curve of the taste aversion produced by s.c. methylnaltrexone and s.c. diallynormorphinium but reduced the lowest effective dose for the other antagonist treatments from three to more than 100 times. Consideration of the data, together with the pharmacokinetic properties of the drugs and the routes of administration used, supported a conclusion that only those aversions involving central antagonist activity show the potentiation effect of chronic morphine treatment. The findings were also discussed with regard to the location of receptors important for aversions produced by opioid antagonists in naive rats.


Subject(s)
Morphine Dependence/physiopathology , Narcotic Antagonists/pharmacology , Taste/drug effects , Animals , Blood-Brain Barrier , Dose-Response Relationship, Drug , Drug Synergism , Infusions, Parenteral , Injections, Subcutaneous , Male , Nalorphine/administration & dosage , Nalorphine/analogs & derivatives , Nalorphine/pharmacokinetics , Nalorphine/pharmacology , Naltrexone/administration & dosage , Naltrexone/analogs & derivatives , Naltrexone/pharmacokinetics , Naltrexone/pharmacology , Narcotic Antagonists/administration & dosage , Narcotic Antagonists/pharmacokinetics , Quaternary Ammonium Compounds , Rats , Rats, Inbred Strains
10.
Braz. j. med. biol. res ; 21(3): 577-83, Mar. 1988. ilus
Article in English | LILACS | ID: lil-60268

ABSTRACT

Morphine and nalorphine were shown to have a peripheral effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. Naloxone antagonized the effect of morphine and nalorphine. Locally administered clonidine had a peripheral effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. The peripheral analgesia of clonidine was antagonized by yohimbine and naloxone. The analgesic effect clonidine was 250-300 times more potent than that of lidocaine. It is suggested that alfa2-adrenergic receptor agonists may active enkephalin-like substances released at the peripheral level


Subject(s)
Guinea Pigs , Animals , Analgesia , Clonidine/administration & dosage , Dose-Response Relationship, Drug , Electric Stimulation , Injections, Subcutaneous , Morphine/administration & dosage , Nalorphine/administration & dosage , Pain Measurement , Vocalization, Animal
11.
Biull Eksp Biol Med ; 97(6): 694-6, 1984 Jun.
Article in Russian | MEDLINE | ID: mdl-6540125

ABSTRACT

During the hypotensive phase of electronocuous shock in rabbits, injection of nalorphine to the hypothalamus provoked elevation in the blood pressure (BP), recovery of the evoked potential (EP) of the sensorimotor brain cortex in response to electrodermal stimulation (EDS) of the hind limb. Injection of the drug to the central gray of the midbrain resulted in an insignificant short-term elevation of the BP followed by its drop. It is concluded that the endogenous opioid system of the hypothalamus is of importance in the genesis of the hypotensive response and suppression of the EP of the rabbit sensorimotor brain cortex in response to EDS during electronocuous shock.


Subject(s)
Blood Pressure/drug effects , Evoked Potentials, Somatosensory/drug effects , Hypothalamus/drug effects , Nalorphine/pharmacology , Stress, Psychological/physiopathology , Animals , Humans , Injections , Nalorphine/administration & dosage , Rabbits
12.
Neirofiziologiia ; 16(2): 263-5, 1984.
Article in Russian | MEDLINE | ID: mdl-6330584

ABSTRACT

The influence of opiatotropic drugs on the sensitivity of lateral hypothalamic neurons to amphetamine in the Wistar rats was studied microinotophoretically . D-met2-pro5-enkephalinamide reinforced the amphetamine reactions of most units studied and nalorphine had no effect. A suggestion is made that differences observed in the action of D-met2-pro5-enkephalinamide and nalorphine on the neuronal responses to amphetamine are due to activation of different opiate receptors.


Subject(s)
Amphetamine/administration & dosage , Enkephalin, Methionine/analogs & derivatives , Hypothalamic Area, Lateral/drug effects , Action Potentials/drug effects , Animals , Drug Interactions , Enkephalin, Methionine/administration & dosage , Male , Nalorphine/administration & dosage , Rats , Rats, Inbred Strains , Receptors, Opioid/drug effects
13.
Ann Rech Vet ; 11(1): 57-67, 1980.
Article in French | MEDLINE | ID: mdl-7436330

ABSTRACT

Two sheep were fitted with permanent cannulus in the first cerebral ventricule and permanent electrodes were stitched to the wall of the reticulum. They were housed in individual pens and fed lucern pellets twice a day (total duration 1.30 hour) at fixed hours. Food intake was weighed. Chewing movements were recorded permanently by means of a submandibular balloon. Reticular motility was recorded by electromyography during feeding periods. Feeding behaviour and rumination were previously recorded during two control periods. No treatment was applied during the first control period of 6 days (Ta). During the second one (Tb), daily intracerebroventricular (ICV) injections of saline (0.2 ml)) were given for 4 consecutive days. During the following 4 days (Na period), the sheep received isovolumic ICV injections of nalorphine (1 mg per day). Saline was injected again ICV for the last 4 days of the experimental period (Tc). During the period of nalorphine administration there was an important fall in the circadian percentage of rumination of one sheep and a total suppression in the other, discarding the possibility of a volumetric effect. There was also a significant decrease of food intake in the two sheep but nalorphine did not modify the frequency of reticular contractions in any case. Regarding to the general behaviour, the drug induced a general excitation with bleating and increased responsiveness to stimuli. Oral activity included compulsive and continuous chewing movement, creaking the teeth, gnawing, nipping and an apparent activity of searching food for up to 15 hours. In conclusion, nalorphine and morphine effects upon the sheep are compared. The effects of the two drugs are exactly the same regarding to the decrease of rumination and feeding intake and the modification of general behaviour, but morphine decreases markedly the reticular rhythm whereas nalorphine does not. Besides, it seems that the animals get tolerant more readily to morphine than to nalorphine.


Subject(s)
Feeding Behavior/drug effects , Mastication/drug effects , Nalorphine/administration & dosage , Sheep/physiology , Animal Feed , Animals , Gastrointestinal Motility/drug effects , Injections, Intraventricular , Male , Nalorphine/pharmacology , Reticulum/drug effects
14.
Prostaglandins ; 18(2): 201-8, 1979 Aug.
Article in English | MEDLINE | ID: mdl-523678

ABSTRACT

Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE2 or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.


Subject(s)
Analgesics , Hyperalgesia/chemically induced , Hyperesthesia/chemically induced , Narcotic Antagonists/pharmacology , Nociceptors/drug effects , Prostaglandins E/pharmacology , Animals , Carrageenan/pharmacology , Enkephalins/pharmacology , Injections, Intraperitoneal , Injections, Intraventricular , Morphine/administration & dosage , Morphine/pharmacology , Nalorphine/administration & dosage , Nalorphine/pharmacology , Naloxone/administration & dosage , Naloxone/pharmacology , Pentazocine/administration & dosage , Pentazocine/pharmacology , Rats
15.
Drug Alcohol Depend ; 3(5): 301-18, 1978 Sep.
Article in English | MEDLINE | ID: mdl-101364

ABSTRACT

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.


Subject(s)
Narcotics/pharmacology , Reinforcement, Psychology , Animals , Dealkylation , Dextropropoxyphene/administration & dosage , Dogs , Haplorhini , Heroin Dependence/psychology , Humans , Methadone/administration & dosage , Methyltransferases/antagonists & inhibitors , Morphine Dependence/psychology , Nalorphine/administration & dosage , Narcotics/administration & dosage , Narcotics/metabolism , Pupil/drug effects , Self Administration , Species Specificity , Time Factors
16.
J Pharmacol Exp Ther ; 204(3): 547-57, 1978 Mar.
Article in English | MEDLINE | ID: mdl-633066

ABSTRACT

A standardized self-administration procedure in rats was used to determine the intravenous self-administration liability of graded doses of various drugs. Self-administration was reliably established with the tested addictive drugs (morphine, heroin, fentanyl and d-amphetamine), but not with the nonaddictive drugs (chlorpromazine and nalorphine). However, 1 out of 14 animals on nalorphine clearly demonstrated self-administering behavior. Self-administration was observed with delta1-tetrahydrocannabinol, but the percentage of animals (40% on the highest dose) that initiated this behavior and the amount of drug intake were low in comparison with amphetamine and narcotics. Concerning the narcotic drugs, approximate ED50 values for self-administration under the described conditions were calculated (morphine: 0.65; heroin: 0.05; fentanyl: 0.0025 mg/kg/injection). Total daily drug intake was related to the unit dose delivered per injection in that a higher drug dosage led to more drug intake. In experiments with heroin, this relationship was not caused by prior forced injections. The approximate ED50 value for amphetamine appeared to be 0.145 mg/kg/injection. Narcotic drug administration resulted in a disturbance of the patterns of food and water intake. Shortly after drug administration food intake was stimulated, followed by an increased consumption of water. The patterns of food and water intake remained disturbed in animals showing self-injecting behavior. With amphetamine both the quantity of food and the frequency of eating were reduced. These effects were observed only temporarily in animals tested without prior forced injections. The present results indicate that measuring the reinforcing efficacy of drugs under strictly defined experimental conditions provides quantitative criteria for intravenous self-administration of drugs in rats.


Subject(s)
Pharmaceutical Preparations/administration & dosage , Self Administration , Animals , Behavior, Animal/drug effects , Body Weight/drug effects , Chlorpromazine/administration & dosage , Dextroamphetamine/administration & dosage , Drinking/drug effects , Dronabinol/administration & dosage , Eating/drug effects , Female , Injections, Intravenous , Nalorphine/administration & dosage , Narcotics/administration & dosage , Rats
18.
Psychopharmacologia ; 46(2): 133-9, 1976 Mar 16.
Article in English | MEDLINE | ID: mdl-986051

ABSTRACT

In rats made dependent on morphine by implantation of morphine pellets, withdrawal, as precipitated by intraventricular injection of morphine antagonists, was compared to withdrawal as precipitated by systemic antagonist application. The results, most clearly those obtained with a hydrophilic compound, diallyl-nor-morphinium-bromide, point to periventricularly located sites of action for the release of most withdrawal signs by antagonists. Jumping, reaching only low levels after i.ventr. injection of levallorphan and nalorphine, was very pronounced when the benzomorphane derivative SH 254, was used. In the case of writhing and diarrhea, the situation is more complicated. Possibly, central as well as peripheral mechanisms are involved in the expression of these signs.


Subject(s)
Morphine Dependence/physiopathology , Morphine/pharmacology , Narcotic Antagonists/administration & dosage , Substance Withdrawal Syndrome/physiopathology , Animals , Cerebral Ventricles/drug effects , Humans , Injections, Intraperitoneal , Injections, Intraventricular , Levallorphan/administration & dosage , Male , Morphinans/administration & dosage , Nalorphine/administration & dosage , Nalorphine/analogs & derivatives , Narcotic Antagonists/pharmacology , Rats , Receptors, Drug , Substance Withdrawal Syndrome/chemically induced
20.
Br Med J ; 1(6001): 96, 1976 Jan 10.
Article in English | MEDLINE | ID: mdl-1244958
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