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1.
Med Mycol ; 60(5)2022 May 28.
Article in English | MEDLINE | ID: mdl-35604675

ABSTRACT

Although a high prevalence of COVID-19-associated pulmonary aspergillosis has been reported, it is still difficult to distinguish between colonization with Aspergillus fumigatus and infection. Concomitantly, similarities between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hypersensitivity pneumonitis were suggested. The objective of this study was to investigate retrospectively if precipitin assays targeting A. fumigatus could have been useful in the management of SARS-CoV-2 patients hospitalized in an Intensive Care Unit (ICU) in 2020. SARS-CoV-2 ICU patients were screened for Aspergillus co-infection using biomarkers (galactomannan antigen, qPCR) and culture of respiratory samples (tracheal aspirates and bronchoalveolar lavage). For all these patients, clinical data, ICU characteristics and microbial results were collected. Electrosyneresis assays were performed using commercial A. fumigatus somatic and metabolic antigens. ELISA were performed using in-house A. fumigatus purified antigen and recombinant antigens.Our study population consisted of 65 predominantly male patients, with a median ICU stay of 22 days, and a global survival rate of 62%. Thirty-five patients had at least one positive marker for Aspergillus species detection. The number of arcs obtained by electrosyneresis using the somatic A. fumigatus antigen was significantly higher for these 35 SARS-CoV-2 ICU patients (P 0.01, Welch's t-test). Our study showed that SARS-CoV-2 ICU patients with a positive marker for Aspergillus species detection more often presented precipitins towards A. fumigatus. Serology assays could be an additional tool to assess the clinical relevance of the Aspergillus species in respiratory samples of SARS-CoV-2 ICU patients. LAY SUMMARY: This study showed retrospectively that precipitin assays, such as electrosyneresis, could be helpful to distinguish between colonization and infection with Aspergillus fumigatus during the management of severe acute respiratory syndrome Coronavirus-2 (SARS CoV-2) patients in an intensive care unit.


Subject(s)
COVID-19 , Invasive Pulmonary Aspergillosis , Animals , Antigens, Fungal , Aspergillus , Aspergillus fumigatus , Biomarkers , COVID-19/diagnosis , COVID-19/veterinary , Female , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/veterinary , Male , Precipitins , Retrospective Studies , SARS-CoV-2
2.
Article in English | MEDLINE | ID: mdl-21880475

ABSTRACT

BACKGROUND: We hypothesized that due to the absence of a dietary source of omega-3 fatty acids, the essential fatty acid (EFA) deficiency model leads to an overestimate of linoleic acid (LA) requirements. METHODS: over 7wk, young rats consumed an EFA diet containing either 0en% linoleate (0LA) and 0en% α-linolenate (0LNA) or a diet containing 0.5en% LNA plus one of seven levels of added LA (0.12-4.0en%; n=6/group). RESULTS: Rats consuming the 0LA-0LNA diet had the lowest final body weight, 34-68% lower LA and arachidonate in plasma and liver, 87% lower LA in epididymal fat, and an 8-20 fold higher eicosatrienoate in plasma, liver and muscle lipids. 0.5LNA completely prevented the lower growth and partly prevented the rise in eicosatrienoate seen in the 0LA-0LNA group. CONCLUSION: Providing dietary LNA at 0.5 en% reduces the rat's physiological requirement for LA by an estimated factor of at least four (0.5en% instead of 2en%). Since LA requirements in humans are also based on the same flawed model of EFA deficiency, it is plausible that they too have been overestimated and should therefore be reinvestigated.


Subject(s)
Dietary Fats/metabolism , Linoleic Acid/metabolism , alpha-Linolenic Acid/metabolism , Animals , Arachidonic Acids/metabolism , Cerebral Cortex/metabolism , Docosahexaenoic Acids/metabolism , Fatty Acids/blood , Fatty Acids, Essential/deficiency , Fatty Acids, Essential/metabolism , Fatty Acids, Unsaturated/metabolism , Liver/metabolism , Male , Muscle, Skeletal/metabolism , Rats , Rats, Wistar , Weight Gain
3.
Behav Brain Res ; 180(2): 119-26, 2007 Jun 18.
Article in English | MEDLINE | ID: mdl-17397943

ABSTRACT

Inattention, hyperactivity and impulsiveness are the main symptoms of the heterogeneous attention-deficit/hyperactivity disorder (ADHD). It has been suggested that ADHD is associated with an imbalance in polyunsaturated fatty acid (PUFA) composition, with abnormal low levels of the main n-3 PUFA, DHA (22: 6n-3). DHA is highly accumulated in nervous tissue membranes and is implicated in neural function. Animal studies have shown that diet-induced lack of DHA in the brain leads to alterations in cognitive processes, but the relationship between DHA and hyperactivity is unclear. We examined the membrane phospholipid fatty acid profile in frontal cortex of rats characterized for attention, impulsiveness and motricity in various environmental contexts to determine the relationship between brain PUFA composition and the symptoms of ADHD. The amounts of n-3 PUFA in the PE were significantly correlated with nocturnal locomotor activity and the locomotor response to novelty: hyperactive individuals had less n-3 PUFA than hypoactive ones. We conclude that spontaneous hyperactivity in rats is the symptom of ADHD that best predicts the n-3 PUFA content of the frontal cortex. This differential model in rats should help to better understand the role of PUFA in several psychopathologies in which PUFA composition is modified.


Subject(s)
Fatty Acids, Omega-3/metabolism , Frontal Lobe/metabolism , Hyperkinesis/metabolism , Hyperkinesis/pathology , Animals , Attention/physiology , Behavior, Animal , Choice Behavior/physiology , Disease Models, Animal , Docosahexaenoic Acids/metabolism , Impulsive Behavior/physiopathology , Male , Motor Activity/physiology , Rats , Rats, Sprague-Dawley , Reaction Time/physiology , Statistics as Topic
4.
Pathol Biol (Paris) ; 50(9): 547-51, 2002 Nov.
Article in French | MEDLINE | ID: mdl-12490418

ABSTRACT

We conducted a prospective study to identify predictors of inappropriateness of surgical prophylaxis. A total of 72 surgeon-anaesthesist pairs participated in data collection. We assessed practices by addressing 5 questions: did the surgical procedure justify the use of antimicrobial prophylaxis, and was it provided? Was the correct agent used? Was the timing of prophylaxis optimal? Was the duration of prophylaxis correct? Was the dose correct? We reviewed 687 procedures, 513 (74.7%) of which were included in the analysis. The proportion of these procedures with totally compliant prescriptions was 41.7%. Of the 156 patients who received an inappropriate drug, 133 (85.3%) received a drug with a broader spectrum than that recommended. Prophylaxis lasted too long in 81 (89.0%) of the 91 patients who received prophylaxis of incorrect duration. Multivariate analysis revealed a clear association between non-compliant prophylaxis and two operation-specific factors: prosthesis implantation (with a relative risk of 2.52) and clean-contaminated operations (with a relative risk of 4.19). More than 50% of patients received inappropriate surgical prophylaxis. Non-observance of guidelines was related to factors that did not influence the infectious potential of the flora.


Subject(s)
Antibiotic Prophylaxis/psychology , Treatment Refusal , Adult , Aged , Aged, 80 and over , Antibiotic Prophylaxis/standards , Female , Humans , Male , Middle Aged , Practice Guidelines as Topic , Premedication/psychology , Premedication/standards , Preoperative Care , Prospective Studies , Surveys and Questionnaires
5.
Pathol Biol (Paris) ; 50(9): 552-9, 2002 Nov.
Article in French | MEDLINE | ID: mdl-12490419

ABSTRACT

All the patients hospitalised at Besançon Hospital between October 2000 and December 2000 were included in a prospective study in order to determine the incidence of bloodstream infections caused by coagulase-negative staphylococci (CNS), the prevalence of decreased susceptibility to glycopeptides and the molecular epidemiology of these pathogens. CNS isolates from bloodstream infections were collected and characterised by analysis of antibiotic susceptibility and restriction fragment length polymorphism using pulsed field gel electrophoresis. Forty-five episodes of CNS bacteremia occurred in 43 patients. The crude incidence of infected patients was 0,51 per 1,000 days of hospitalisation. These 45 bacteremia represented 23.3% of the total number of bacteraemia. Forty three of 45 bacteremia were studied, 36 were positive with a single PFGE pattern, 5 bacteraemias with 2 PFGE patterns, and 2 bacteraemias with 3 PFGE patterns. We identified 52 distinct PFGE patterns and 42 major PFGE patterns (35 were isolated in a single patient, 5 in 2 patients and 2 in 3 patients). The dendrogram generated showed deep but limited branching, each large branch corresponding to a species. Of these CNS isolates, 28.8% and 25.0% showed decreased susceptibility to teicoplanin, with the reference method and E-test respectively. The 16 strains belonging to multiple PFGE patterns were not more resistant to teicoplanin. Clonal dissemination did not seem to play a major role in the spread of glycopeptides resistance among CNS.


Subject(s)
Bacteremia/etiology , Drug Resistance, Bacterial , Staphylococcal Infections/epidemiology , Staphylococcus/drug effects , Teicoplanin/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Bacteremia/epidemiology , Bacteremia/microbiology , Cross Infection/microbiology , Drug Resistance, Multiple , Female , France/epidemiology , Genotype , Humans , Incidence , Male , Middle Aged , Staphylococcal Infections/complications , Staphylococcus/classification , Staphylococcus/isolation & purification , Teicoplanin/pharmacology
6.
Ann Fr Anesth Reanim ; 21(8): 634-42, 2002 Oct.
Article in French | MEDLINE | ID: mdl-12471784

ABSTRACT

OBJECTIVES: To assess the practices of surgical antimicrobial prophylaxis in the Franche-Comté region of France before and after the implementation of information program. STUDY DESIGN: Prospective multicenter transversal study type before/after. The information program included a feedback on the observed results during the period before and a meeting with opinion leaders. PATIENTS AND METHODS: Data were collected by 28 pairs of surgeons/anaesthetists. Prescriptions were analysed to answer five questions about antibiotic prophylaxis practices in surgery: did the surgical procedure require antibiotic prophylaxis and was this carried out? Was the appropriate antibiotic used? Was the timing of the first injection optimal? Was the total duration of the treatment correct? Was the dose correct? Our data were compared to national recommendations (updated in 1999). RESULTS: The overall frequency of conformity was about 40% both before and after the implementation of an information/awareness campaign. Only the conformity of the total duration of the prophylaxis was significantly higher after the action, but only for interventions that lasted less than two hours. [RR = 2.09 (1.32-3.31), p = 0.001]. This improvement in the total duration of regulation seemed to be related to the more frequent use of written protocols in the surgical units. CONCLUSION: Our study confirms that information campaign have little effect within the framework of the good use of antibiotics. We agree with the experts who claim that only an overall strategy including organization, education and restriction will really improve the frequency of conformity of the practices of surgical prophylaxis.


Subject(s)
Antibiotic Prophylaxis/standards , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Drug Prescriptions/standards , Education, Continuing , Female , France , Guidelines as Topic , Humans , Male , Middle Aged , Prospective Studies
7.
Pharm World Sci ; 24(3): 95-9, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12136746

ABSTRACT

OBJECTIVE: A prospective multicentre study was conducted to assess major aspects of surgical prophylaxis and to determine whether inappropriate antimicrobial prophylaxis was a factor associated (risk or protective factor) with surgical site infection (SSI). METHOD: Surgical prophylaxis practices were assessed by analysing four variables: indication, antimicrobial agent, timing and duration. Univariate and multivariate analyses were carried out to identify predictors of SSI among patient-specific, operation-specific and antimicrobial prophylaxis-specific factors. RESULTS: The frequency of SSI was 2.7% (13 SSI in 474 observations). Total compliance of the prescription with guidelines was observed in 41.1% of cases (195 prescriptions). Of the 139 patients who received an inappropriate drug, 126 (90.6%) received a drug with a broader spectrum than the recommended drug. Prophylaxis was prolonged in 71 (87.7%) of the 81 patients who received prophylaxis for inappropriate lengths of time and 43 (61.4%) of the 70 patients who did not receive prophylaxis at the optimal moment were treated too late. Multivariate analysis clearly demonstrated that SSI was associated with multiple procedures (relative risk 8.5), short duration of prophylaxis (relative risk 12.7) and long-term therapy with antimicrobial agents during the previous year (relative risk 8.8). CONCLUSIONS: The ecological risk of the emergence of resistance associated with the frequent use of broad-spectrum antibiotics and prophylaxis for longer periods was not offset by individual benefit to the patients who received inappropriate prophylaxis.


Subject(s)
Antibiotic Prophylaxis/statistics & numerical data , Guideline Adherence/statistics & numerical data , Practice Guidelines as Topic , Surgical Wound Infection/drug therapy , Surgical Wound Infection/epidemiology , Adult , Aged , Antibiotic Prophylaxis/methods , Confidence Intervals , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prospective Studies
8.
J Hosp Infect ; 51(3): 207-14, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12144800

ABSTRACT

The purpose of our study was to assess the prevalence of coagulase-negative staphylococci (CoNS) isolates with reduced susceptibility to glycopeptides among the isolates responsible for bloodstream infections and to describe the epidemiology of these isolates. CoNS isolates from bloodstream infections were collected and characterized by analysis of antibiotic susceptibility and restriction fragment length polymorphism using pulsed-field gel electrophoresis. The medical records of patients with positive cultures and trends in glycopeptide use were reviewed to determine the effect of previous antibiotic treatment on the susceptibility profile of these organisms. The crude incidence of CoNS bacteraemia was 0.51 per 1000 days of hospitalization. The 15 (28.8%) strains identified as having decreased susceptibility to teicoplanin by the reference method were all hospital-acquired and displayed 13 different DNA patterns. The relative risk of harbouring strains with decreased susceptibility to teicoplanin was 3.55 among patients previously treated with vancomycin (confidence interval 95%: 2.15-5.85). The teicoplanin consumption in our institution was constant and represented about 27% of the glycopeptide consumption in daily defined doses. The implementation of programmes aiming to reduce the unnecessary use of glycopeptides should have a significant impact on the reduced-susceptibility rate because strains probably become resistant as a result of antibiotic pressure.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Staphylococcal Infections/drug therapy , Staphylococcus/drug effects , Teicoplanin/pharmacology , Adult , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Female , Humans , Incidence , Male , Microbial Sensitivity Tests , Middle Aged , Molecular Epidemiology , Risk Factors , Staphylococcal Infections/epidemiology , Staphylococcus/isolation & purification , Staphylococcus/pathogenicity
9.
Chir Main ; 21(3): 176-81, 2002 May.
Article in French | MEDLINE | ID: mdl-12116829

ABSTRACT

AIM: Apply the principles of elastic intra-medullary nailing developed by Metaizeau for children, to bone fixation of bones of the hand. METHOD: Retrospective review of 43 patients treated between 1995 and 1999 for fracture of one or more bones of the hand. Thirty five concerned the right hand, 11 the left; 54 involved metacarpal fractures and 2 fractures of the phalanx. Only those patients whose lesions were considered mended were taken into account in this study. RESULTS: In 32 cases, bone fixation was completed with the use of a single pre-stressed pin, in 24 cases 2 prestressed pins forming a double arc were used. The delay in removal of material varied from between 35 days to 4 1/2 months. In three cases it required a dynamic splint treatment. Functional re-education was prescribed for two patients. Eight patients were lost for follow up. Fourty eight were followed with complete recovery of joint range of motion. We deplored one necrosis of the skin due to the contusion at the time of the initial trauma, one delayed healing after an animal bite required keeping the material in place for 4 months, one case of infection; in another case insufficient stabilization by the ECMES resulted in a 10 degrees mal-union of the metacarpal diaphysis. Three times the site of a fracture had to be opened in order to perform bone fixation. CONCLUSION: The ECMES appears perfectly suitable for bone fixation of the diaphysis of bones of the hand and certain metaphyseal and epiphyseal fractures. Small incisions help to avoid unbecoming scars and adhesions and foster a rapid recovery of function.


Subject(s)
Bone Nails , Fracture Fixation, Internal/methods , Hand Injuries/surgery , Child, Preschool , Female , Humans , Infant , Male , Metacarpus/injuries , Metacarpus/surgery , Retrospective Studies , Treatment Outcome
10.
J Hosp Infect ; 49(2): 135-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11567560

ABSTRACT

A prospective study was conducted to assess the appropriateness of surgical antibiotic prophylaxis. A total of 72 surgeon-anaesthesist pairs participated in data collection, which assessed five variables: did the surgical procedure justify the use of antimicrobial prophylaxis and was it given? was an appropriate agent used?, is the timing of administration optimal?, is the duration of prophylaxis correct?, and is a proper dose given? Of the 687 procedures reviewed, 513 (74.7%) were entered in the analysis. Of these procedures, the rate of totally compliant prescriptions was 41.7%. Among the 117 patients who received an inappropriate drug, 112 (95.7%) received a drug with a broader spectrum of activity than that recommended. Prolonged prophylaxis occurred in 80 (87.9%) of the 91 patients who received prophylaxis with an incorrect duration. In conclusion, compliance with the principles of prophylactic antimicrobial administration should be strictly reviewed and conducting such audits should be part of the routine activity of infection control teams.


Subject(s)
Antibiotic Prophylaxis , Specialties, Surgical , France , Humans , Patient Compliance , Prospective Studies
11.
Ann Chir ; 126(5): 463-71, 2001 Jun.
Article in French | MEDLINE | ID: mdl-11447801

ABSTRACT

AIM OF THE STUDY: To evaluate the practice of antibiotic prophylaxis for surgery in the Franche-Comté region of France. MATERIALS AND METHODS: A total of 36 surgical teams (72 pairs surgeons/anaesthesists) participated in data collection. Five variables describing practices concerning antibiotic prophylaxis for surgery were compared to national recommendations: did the surgical procedure require antibiotic prophylaxis and was it carried out? Was the antibiotic used appropriately? Was the timing of the first injection optimal? Was the total duration of the treatment correct? Was the dose correct? RESULTS: Among the 687 operations for which data were collected, 513 (74.7%) that corresponded to class 1 or 2 Altemeier operations for which the Société Française d'Anesthésie et Réanimation (SFAR) had drawn up recommendations were analysed in order to answer these questions. The overall frequency of conformity with the regulations was 40% for these 513 operations. Of the 156 patients who did not receive the recommended antibiotic, 133 (85.5%) received an antibiotic with an activity range wider than that of the recommended antibiotic. The duration of prophylaxis was longer than recommended in 80 (87.9%) out of the 91 patients for whom the duration of antibiotic prophylaxis did not respect the recommendations. CONCLUSIONS: This prospective surveillance showed that less than 50% of patients received an antibiotic prophylaxis that was conformed to the regulations. To ensure the efficiency of prophylaxis and to prevent deleterious effects, such as the emergence of antibiotic-resistant bacteria, the recommendations must be regularly respected. Frequent audits of practices should be carried out by the teams responsible for fighting nosocomial infections.


Subject(s)
Antibiotic Prophylaxis , Guideline Adherence , Practice Guidelines as Topic , Surgical Wound Infection/prevention & control , Adult , Aged , Aged, 80 and over , Female , France , Humans , Male , Middle Aged , Prospective Studies
12.
Chir Main ; 18(3): 179-83, 1999.
Article in English | MEDLINE | ID: mdl-10855317

ABSTRACT

In huge median nerve losses and in some brachial plexus lesions, absence of sensation over the pulps of the index finger and the thumb preclude their use without visual control. Currently, end-to-side anastomosis is a new option available (when the ulnar nerve is intact) but we have reviewed the results of 7 cases of nerve anastomosis between the sensory branches of the radial nerve and the collateral nerves of the thumb (ulnar) and index finger (radial). Palmar translocation of the donor nerve, as classically performed, was used in two cases and the technique was subsequently modified to provide a better nerve suture by dorsal transfer of the collateral nerves of the thumb and index. Two sequellae of brachial plexus lesions and 5 cases of extensive defects of the median nerve were reviewed at a mean follow up of 5 years. With the classical technique the two point discrimination was 15 mm in one case and more in the other; with the modified technique, 4 patients achieved a thumb discriminaTion of 9 mm, 12 mm (2 cases) and 13 mm.


Subject(s)
Fingers/physiology , Nerve Transfer , Radial Nerve/surgery , Sensation/physiology , Thumb/innervation , Adult , Anastomosis, Surgical/methods , Brachial Plexus/injuries , Fingers/innervation , Follow-Up Studies , Hand Strength/physiology , Humans , Median Nerve/injuries , Middle Aged , Muscle, Skeletal/innervation , Muscle, Skeletal/surgery , Sensory Thresholds/physiology , Tendons/surgery , Thumb/physiology , Touch/physiology , Ulnar Nerve/surgery
13.
Ann Chir Plast Esthet ; 43(6): 593-9, 1998 Dec.
Article in French | MEDLINE | ID: mdl-9972651

ABSTRACT

Among the recent advances in the field of Dupuytren's contracture, the authors reviewed a series of 171 patients treated by percutaneous needle fasciotomy. Among the 198 hands (241 fingers), 65 were reviewed with a mean follow-up of 2.5 years. Mean age was 62 years and delay between onset and treatment 6.8 years. Rupture of the cords was performed only in the palm in 154 cases, palmo-digital in 82 and purely digital in 5 cases. Complications were rare and benign without tendon or vascular bundle injury. Postoperative gain was essentially observed on the metacarpo-phalangeal joint and recurrence rate was high despite the short follow-up (progression of the disease 54% of cases). The ideal indication for this simple and reliable technique is an elderly patient with a prominent cord and predominant lack of metacarpophalangeal extension.


Subject(s)
Dupuytren Contracture/surgery , Fasciotomy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Intraoperative Complications , Male , Middle Aged , Postoperative Complications , Recurrence , Time Factors
14.
Neuropharmacology ; 31(3): 293-8, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1321359

ABSTRACT

The coexistence of endogenous opioid systems and dopaminergic neurones in the midbrain tegmental area suggests functional interactions between dopamine and enkephalins. Nevertheless, the identification of the specific opioid receptors associated with modulation of tegmental dopamine activity and its behavioural concomitants on motility and reward is far from clear, considering the mixed nature of the ligands usually employed. In this way, kelatorphan, a potent inhibitor of enkephalinases and selective agonists for mu- and delta-opioid receptor subtypes (DAGO and DSTBULET, respectively) were infused directly into the ventral tegmental area of the rat to study the role of endogenous enkephalins and opioid receptors in regulating spontaneous motor activity and intracranial self-stimulation behaviour. A greater increase in the rate of intracranial self-stimulation behaviour was found after activation of mu-opioid receptors in the ventral tegmental area, as compared to activation of delta-opioid receptors, whereas enhancement of endogenous enkephalins by inhibiting their metabolism through kelatorphan, reduced the rate of intracranial self-stimulation behaviour. On the contrary, spontaneous motor activity was reduced by the delta-opioid receptor agonist, whereas kelatorphan increased the movements of the animal. Taken together, these results show that inhibition of the metabolism of enkephalins in the ventral tegmental area decreased positive reinforcement from the lateral hypothalamic medial forebrain bundle and increased spontaneous movements. On the contrary, activation of both mu- or delta-opioid receptors in the ventral tegmental area significantly increased self-stimulation and decreased spontaneous motor activity, supporting the view that different mechanisms underlie the behavioural effects, resulting from enhancement of endogenous enkephalins and from activation of specific opioid receptors in the ventral mesencephalon.


Subject(s)
Enkephalins/metabolism , Mesencephalon/drug effects , Motor Activity/drug effects , Receptors, Opioid/metabolism , Reward , Animals , Brain/anatomy & histology , Brain/drug effects , Dipeptides/pharmacology , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Enkephalins/administration & dosage , Enkephalins/pharmacology , Male , Oligopeptides/pharmacology , Rats , Rats, Inbred Strains , Receptors, Opioid, delta , Receptors, Opioid, mu , Self Stimulation/drug effects
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