Evaluation of C-reactive protein/albumin ratio and its relationship with survival in dogs with acute pancreatitis.

Aims: To evaluate the association between the C-reactive protein (CRP)/albumin (ALB) ratio and survival in dogs with acute pancreatitis and its use as a prognostic marker for survival. Methods: Medical records of a veterinary referral hospital in Italy were retrospectively searched for dogs that were admitted with acute pancreatitis between January 2015 and April 2019, in which the concentrations of CRP and ALB in serum were measured at admission. The CRP/ALB ratio was calculated and the time between admission and discharge or death was recorded. Mortality rates overall and for dogs that died within 2 days of admission were calculated. A univariable Cox proportional hazard model was used to assess the relationship between survival time and CRP/ALB ratio. Results: Seventy-one dogs were included in the study. Of these, 19 died within 2 days of presentation; an early mortality rate of 26.8%, while 27 died before discharge for an overall mortality rated of 38%. Dogs with higher CRP/ALB ratio had a significantly greater mortality rate than dogs with lower CRP/ALB ratio: for every 1-unit increase in CRP/ALB ratio, the hazard of death over the study period increased by 130% (hazard ratio = 2.34; 95% CI = 1.53-3.58; p < 0.001). The optimal CRP/ALB ratio cut-off point for predicting mortality was 0.56, with a sensitivity and specificity of 88.9% and 68.2%, respectively (AUC = 0.82; p < 0.001). Conclusions: As in humans, the CRP/ALB ratio, may be a promising, though not particularly specific, prognostic marker for increased risk of death in dogs with acute pancreatitis.

Fractional excretion of electrolytes and neutrophil gelatinase-associated lipocalin as early biomarkers of acute kidney injury in dogs with acute pancreatitis.

OBJECTIVES: To determine if fractional excretion of urinary electrolytes and neutrophil gelatinase-associated lipocalin could detect different degrees of kidney injury in dogs with naturally occurring acute pancreatitis. MATERIALS AND METHODS: We included dogs with acute pancreatitis. Dogs with a history of kidney disease, urinary tract infection, dogs which received potentially nephrotoxic drugs and dogs managed with haemodialysis were excluded. Acute kidney injury was diagnosed if there was an acute onset of clinical signs, haemato-chemical results compatible with acute kidney injury. Students or staff-owned dogs were selected to build the healthy group. RESULTS: The study population was composed of 53 dogs: acute pancreatitis with AKI (n=15), acute pancreatitis alone (n=23), and healthy dogs (n=15). In dogs with acute pancreatitis and AKI, all the FEs of urine electrolytes were significantly higher than dogs with acute pancreatitis alone and healthy ones. Dogs with acute pancreatitis alone had higher uNGAL/uCr than healthy dogs (median 54 ng/mg vs. 0.1 ng/mg) and lower compared to AP-AKI patients (54 ng/mg vs 209 ng/mg). CLINICAL SIGNIFICANCE: Some fractional excretion of electrolytes are increased acute kidney injury dogs, however their role in the early detection of renal injury in acute pancreatitis dogs remains doubtful. On the contrary, urinary neutrophil gelatinase-associated lipocalin had higher concentrations in dogs with acute pancreatitis with or without acute kidney injury compared to healthy controls, suggesting that it may be used as an early marker of renal tubular damage in acute pancreatitis dogs.

The erythrocyte sedimentation rate (ESR) in canine inflammation.

The clinical application of the erythrocyte sedimentation rate (ESR) assay is challenging due to its long processing time. However, in 2020 a new automated instrument for veterinary ESR was released and validated. This study sought: (1) to refine the proposed reference range (reference interval, RI) for canine ESR; (2) to compare the ESR values of healthy and sick dogs; and (3) to correlate ESR with other inflammatory markers such as C-reactive protein (CRP), fibrinogen, albumin:globulin ratio (A/G), and neutrophil-to-lymphocyte ratio (NLR); and also (4) to study ESR behavior across illnesses of varying durations. A prospective cohort study of 396 client-owned dogs (n = 120 healthy and n = 276 sick dogs) was conducted. Animals with a full clinical evaluation, complete hematobiochemical profile and a final diagnosis were included. ESR was performed according to manufacturer's instructions using the same 1 mL K3-EDTA tube used for the complete blood count. The RI was established at 1-8 mm/h in 14 min. Sick dogs had a significantly faster ESR (median 10 mm/h) than healthy dogs (median 1 mm/h; P < 0.0001). ESR was positively correlated with NLR (r = 0.36), CRP (r = 0.18) and fibrinogen (r = 0.56) and negatively correlated with A/G (r = -0.37). Dogs with an acute-on-chronic disease had the highest ESR values (median 17 mm/h) compared with either acute (median 11 mm/h; P < 0.001) or chronic diseases (median 7 mm/h; P = 0.001). ESR was confirmed as a reliable canine inflammatory marker, positively correlating with the main inflammatory markers in dogs and significantly different between sick and healthy dogs. The ESR assay appears useful especially in dogs with an acute clinical presentation, with or without an underlying chronic condition.

Oesophagostomy tube complications in azotaemic dogs: 139 cases (2015 to 2019).

OBJECTIVES: To retrospectively assess the rate of oesophagostomy tube-related complications in azotaemic dogs, the influence of the oesophagostomy tube (o-tube) duration and the therapeutic approach (medical versus haemodialysis) on the complication rate. MATERIALS AND METHODS: Medical records were retrospectively reviewed in order to identify azotaemic dogswhich underwent o-tube placement. o-Tube duration (short-term versus long-term), time of o-tube change, therapeutic approach (medical versus haemodialysis), prevalence of minor (malposition, suture related, inflammation, muco-purulent discharge, abscess) and major (haemorrhage, malposition, obstruction, dislodgement, vomiting of the tube, food coming from the stoma) o-tube-related complications were extracted. Univariate and multivariate logistic regression analysis were performed to identify the risk factors for o-tube-related complications. RESULTS: Tube-related complications were reported in 74 of 139 dogs (53%). Minor complications were reported in 66 of 74 (89%) and major complications in eight of 74 (11%). In azotaemic dogs, o-tube indwelling time (odds ratio (OR) 1.03; 95% confidence interval (CI) 1.01 to 1.05), and the use of haemodialysis (OR 40.12; 95% CI 9.18 to 175.20) were risk factors for o-tube-related complications. CLINICAL SIGNIFICANCE: The majority of o-tube-related complications were minor, and easily manageable, with no need of hospitalisation, tube-removal or euthanasia. In azotaemic dogs, the use of haemodialysis was strongly associated with a higher risk of o-tube-related complications, possibly as a consequence of the presence of the neck bandage.

Molecular structure of DNA by scanning tunneling microscopy.

Uncoated DNA molecules marked with an activated tris(l-aziridinyl) phosphine oxide (TAPO) solution were deposited on gold substrates and imaged in air with the use of a high-resolution scanning tunneling microscope (STM). Constant-current and gap-modulated STM images show clear evidence of the helicity of the DNA structure: pitch periodicity ranges from 25 to 35 angstroms, whereas the average diameter is 20 angstroms. Molecular structure within a single helix turn was also observed.

Acute pancreatitis and acute kidney injury in dogs.

Acute pancreatitis and acute kidney injury are well-documented comorbidities in human medicine. Dogs that develop acute kidney injury during hospitalization have significantly higher mortality rates than those that do not. The aim of this study was to evaluate the prevalence of acute kidney injury in dogs with acute pancreatitis and the prognostic value of various clinicopathological parameters. Cases of acute pancreatitis presented between January 2012 and June 2016 were identified. The diagnosis of acute pancreatitis was based on two or more of the following clinical signs: abdominal pain, diarrhea, vomiting or anorexia/hyporexia, no other abdominal extra-pancreatic diseases at abdominal ultrasound, and abnormal SNAP cPL test. Diagnosis of acute kidney injury was based on the guidelines of the International Renal Interest Society. Dogs were classified into survivors and non-survivors. Serum creatinine, urea, amylase, total calcium, total cholesterol, C-reactive protein, WBC and band neutrophils were evaluated at admission. Clinical severity index was calculated at admission. Clinical and clinicopathological data were compared between survivors and non-survivors. Sixty-five dogs with acute pancreatitis were assessed. Clinical severity index≥6.5 were associated with poor outcome (P=0.0011). Serum urea and creatinine concentrations at admission were significantly lower in survivors than non-survivors (P<0.0001 and P=0.0002, respectively). Acute kidney injury was diagnosed in 17/65 dogs (26.2%) and was associated with poor outcome (P<0.0001). Oligo-anuria was associated with poor outcome (P=0.0294). Increased clinical severity index and azotemia in dogs with acute pancreatitis were associated with an increased risk of mortality. Acute kidney injury may be a comorbidity of canine acute pancreatitis. The presence of oligo-anuria is associated with poor outcome.

Neutrophil-to-lymphocyte ratio, nucleated red blood cells and erythrocyte abnormalities in canine systemic inflammatory response syndrome.

Systemic inflammatory response syndrome (SIRS) is the manifestation of the systemic response to an infectious or non-infectious disease. We evaluated the association between erythrocyte parameters, including nucleated red blood cells (NRBCs) and leukocyte ratios (NLR, neutrophil-to-lymphocyte ratio; BLR, band neutrophil-to-lymphocyte ratio; BLNR, band neutrophil-to-neutrophil-to-lymphocyte ratio). A review of the medical records was conducted searching SIRS dogs among those admitted to our intensive care unit and a SIRS grading was obtained based on how many criteria were fulfilled. The Acute Patient Physiology and Laboratory Evaluation (APPLEfast) score was assessed in each dog. Survival rate was assessed 15 days after admission. Dogs with clinical and/or clinicopathological signs of hemolytic or hemorrhagic disorders were excluded. Dogs with ≥2 criteria of SIRS along with a documented underlying infectious cause were recorded as septic (32/90, 35%). A SIRS grading >2 (p = .001) and an APPLEfast score > 25 (p = .03) were associated with mortality. Twenty-two of SIRS dogs (24%) showed circulating NRBCs. The occurrence of circulating NRBCs was associated with the mortality in SIRS groups (p = .0025). The median NLR was 11.69 and NLR was lower in septic dogs compared to non-septic ones (p = .0272). APPLEfast, SIRS grading and circulating NRBCs may be considered as negative prognostic factors in canine SIRS. NLR could be a useful tool in dogs with SIRS, which was significantly lower in the septic group. Further prospective, large-scale studies investigating BLR and BNLR in canine SIRS are warranted.

LARS™ in ACL reconstruction: evaluation of 60 cases with 5-year minimum follow-up.

PURPOSE: The injury of anterior cruciate ligament (ACL) causes joint instability and, in the absence of adequate treatment, progressive joint deterioration, meniscal lesions and development of post-traumatic osteoarthritis. METHODS: The purpose of this study was to evaluate the clinical, functional and radiographic outcomes and complications in a consecutive case series of 60 patients with minimum follow-up of 5 years who underwent an arthroscopic surgery for ACL reconstruction using LARS™ ligament. Patients with concomitant meniscal or chondral lesions in the same knee were excluded. RESULTS: The subjective evaluation of the patients involved in the study (Lysholm score, IKDC score and Tegner activity level scale) shows good/excellent results. The range of movement is optimal in most patients, and pain symptoms are considered mild. A total of 31.25% of the patients did not change their lifestyle that they had before the injury. None of the patients underwent resurgery in the same knee. In 85.4% of cases, X-ray images showed no signs of osteoarthritis after ACL reconstruction. CONCLUSIONS: Comparable with other series showed in the literature, this study assesses that the use of LARS™ in reconstruction of ACL is an excellent option for treating >40-year-old patients requesting rapid return to daily activities/sports also at the first surgery. By restoring knee stability, articular degeneration at short and medium follow-up was avoided.

Social modulation of risky decision-making in rats (Rattus norvegicus) and tufted capuchin monkeys (Sapajus spp.).

Both human and non-human animals frequently deal with risky decisions in a social environment. Nevertheless, the influence of the social context on decision-making has been scarcely investigated. Here, we evaluated for the first time whether the presence of a conspecific influences risk preferences in rats and in tufted capuchin monkeys. Subjects received a series of choices between a constant, safe option and a variable, risky option, both alone (Alone condition) and when paired with a conspecific (Paired condition). The average payoff of the risky option was always lower than that of the safe option. Overall, the two species differed in their attitude towards risk: whereas rats were indifferent between options, capuchins exhibited a preference for the safe option. In both species, risk preferences changed in the Paired condition compared to the Alone condition, although in an opposite way. Whereas rats increased their risk preferences over time when paired with a conspecific, capuchins chose the risky option less in the Paired condition than in the Alone condition. Moreover, whereas anxiety-like behaviours decreased across sessions in rats, these behaviours where more represented in the Paired condition than in the Alone condition in capuchins. Thus, our findings extends to two distantly-related non-human species the evidence, so far available for human beings, that a decrease in anxiety corresponds to an increase in risk preferences, and vice versa. This suggests that the modulation of risk preferences by social influences observed in rats and capuchin monkeys may rely on a common, evolutionarily ancient, mechanism.

Do Tuscan people adhere to meningococcal C vaccination during an emergency campaign?

OBJECTIVES: Tuscany region (Italy) recorded a rise in the number of meningococcal disease cases between January 2015 and February 2016, (52 cases) compared to 2014 (16 cases). The aim of this study was to describe the emergency meningococcal C (MenC) vaccination programme in Tuscany and the population's adherence to the activities performed in the Local Health Unit (LHU) of Florence. METHODS: The MenC vaccination programme and the planning of the prevention and communication activities were analysed in the LHU of Florence. As an indicator of population's adherence, the vaccination coverage (VC) during the emergency campaign was investigated and adverse drug reactions (ADR) surveillance was reported. RESULTS: The communication campaign included a dedicated toll-free telephone number, press releases (newspapers, radio, television, websites), and informative letters addressed to mayors, secondary schools, and sports associations. Citizens aged 11-20 years were the primary target of the campaign. Due to the high incidence of cases among older people, the vaccination was extended to subjects over 45 years. The population's adherence to the vaccination campaign was satisfactory: VC reached 47.1% for the primary target. The ADR reporting rate (3.1/10,000) on meningococcal vaccine in our study confirmed the safety of the vaccination. CONCLUSIONS: In 2017, only 10 cases of invasive meningococcal diseases (IMD) were reported, suggesting the effectiveness of the immunization campaign. Similar VC during emergency MenC vaccination programmes have been reached in other Italian regions and other EU countries, too. The achievement of greater vaccination coverage is restricted by a sentiment of hesitancy towards vaccines among the general population.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis.

OBJECTIVE: To evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice. DESIGN: Retrospective study between January 2010 and December 2013. METHODS: The diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non-survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non-survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated. RESULTS: The study enrolled 50 client-owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome. Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 µmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32-118.48) and hyponatraemia (OR 4.9; 95% CI 1.36-17.64) were associated with increased risk of death. CONCLUSIONS: In dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death.

Naltrexone, naltrindole, and CTOP block cocaine-induced sensitization to seizures and death.

I.c.v. injection for 9 days of either naltexone (NTX) (5, 10, 20, 40 micrograms/rat) or a selective mu peptide (CTOP) (0.125, 0.25, 0.5, 1, 3, 6 micrograms/rat) or delta (naltrindole) (NLT) (5, 10, 20 micrograms/rat) subtype opioid receptor antagonist affected sensitization to cocaine (COC) (50 mg/kg, i.p.) administered 10 min after. NTX (5 and 40 micrograms/rat), NLT (10 and 20 micrograms/rat), and the peptide CTOP (0.25-0.5 microgram/rat) attenuated seizure parameters (percent of animals showing seizures, mean score and latency) in a day-related manner. The DD50 (days to reach 50% of death) value for COC was 2.69, whereas it was 9.67 and 7.27 for NTX 5 and 40 micrograms/rat, 8.59 for NLT (10 micrograms/rat), and 6.11, 5.95, and 4.30 for CTOP (0.25, 0.5, and 1 microgram/rat respectively). These findings suggest a concurrent involvement of mu- and delta-opioid receptor subtype in COC-induced sensitization to toxic effects.

Cerebral sites of central action of dermorphin on intestinal motility in the rat.

Dermorphin (DM), microinjected at 0.4 nmoles/rat into various sites of the periaqueductal gray matter (PAG), provokes complete inhibition of intestinal propulsion always coupled with full analgesia and catalepsy. When electrolytic lesions were made in the raphe magnus nucleus (NRM) a slight but significant reduction of intestinal inhibition evoked by DM into the PAG was observed. In contrast, pretreatment into the NRM 10 days before DM with a selective antiserotoninergic agent (5,6 DHT 15 microgram/rat), did not influence intestinal inhibition. As expected, both lesions reduced DM-induced analgesia but catalepsy was not affected. DM-induced inhibition of intestinal transit was therefore unaffected by subdiaphragmatic vagotomy. Finally, some other central brain regions were found sensitive to DM for the above effects such as the lateral and medial hypothalamus and mid-line thalamus. Negative results were obtained for the supraoptic nuclei and postero-medial cortical amygdaloid nucleus. Some considerations are put forward about the existence in the central nervous system of selective areas involved in intestinal modulation and their relationship with those mediating other opiate behavioural effects.

Central pharmacological activities and opiate receptor binding studies of some dermorphin analogs.

A series of dermorphin-like compounds were injected intracerebroventricularly in the rat to assess in vivo their effects on intestinal motility and analgesia. In vitro they were tested by binding assay using 3H-naloxone as radioligand or by guinea pig ileum bioassay. The synthetic peptides were less potent than dermorphin in inhibiting intestinal transit and in producing analgesia, or even inactive up to doses 30 times the dermorphin ED50. This reduction in pharmacological activity was coupled with a decrease in binding potency. The 3H-naloxone binding studies in the absence or presence of Na+ indicated that Na+ reduced the interaction of dermorphin and its analogs with brain opiate receptors. Only the dibenzyl derivative was slightly affected by sodium, suggesting a dual action for this peptide, as confirmed by preliminary data from guinea pig ileum bioassay.

Central and peripheral components of dermorphin's effect on rat intestinal propulsion in comparison to morphine.

Dermorphin, injected intracerebroventricularly (ICV) to rats, provokes, like to morphine, an inhibition of intestinal propulsion linearly related to the log of the administered doses (in the range from 0.06 to 0.56 micrograms/rat), but it is 143 times more active than morphine. Naloxone, ICV or IP, antagonizes dermorphin less effectively than morphine. Quaternary naloxone ICV administered antagonizes the intestinal effect of ICV dermorphin, while IP administered it is not effective until 8 mg/kg. The dose of dermorphin maximally active by the ICV route (0.56 micrograms/rat) is completely inactive when injected IP. Increasing doses of dermorphin IP (from 12 to 6400 micrograms/kg) inhibit intestinal propulsion to the same extent irrespectively of the doses employed, but never by more than 50%. Only a high dose of naloxone (30 mg/kg/IP) antagonizes this IP effect. The central and peripheral components of this intestinal effect of dermorphin are discussed.

Further investigations on neurotensin as central modulator of intestinal motility in rats.

Previous studies have shown that neurotensin (NT) administered intracerebroventricularly (i.c.v.) to rats provokes an inhibition of intestinal propulsion linearly related to the log of administered doses. In the present study it is demonstrated that, in contrast to morphine, repeated i.c.v. administrations of NT (2.5 nmol/rat/day) did not result in tolerance to the intestinal effect. Naloxone (Nx) administered i.c.v. fully antagonized the intestinal inhibition of i.c.v. morphine, but did not significantly alter the NT effect. However, centrally administered thyrotropin-releasing hormone (TRH) inhibited NT-induced (but not morphine-induced) intestinal inhibition. Direct microinjections of NT into the periaqueductal gray matter (PAG) produced complete inhibition of intestinal propulsion when the microinjections were localized in the dorsal portion. Finally, subdiaphragmatic vagotomy totally abolished the inhibition induced by NT into the PAG, while morphine was not affected. Some considerations are put forward concerning the existence in the central nervous system of a peptidergic pathway modulating intestinal function.

Dermorphin interaction with peripheral opioid receptors.

The interaction of dermorphin with different peripheral opioid receptor subtypes was investigated in vitro, using the guinea pig ileum as representative tissue for mu, the mouse vas deferens for delta, the rabbit vas deferens for kappa and the rat vas deferens for epsilon. The effect of dermorphin on each tissue preparation was compared with that of selective mu, delta, kappa epsilon agonists respectively morphine, met-enkephalinamide, ethylketocyclazocine and camel beta-endorphin. Antagonism with naloxone was also tested and calculated as Ke. It is concluded that dermorphin mainly interacts with the mu receptors, although it also binds to epsilon receptors; the interaction with delta receptors is questionable, and the kappa receptors are unaffected.

Effect of intracerebroventricular administration of morphine upon intestinal motility in rat and its antagonism with naloxone.

Morphine, intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) administered to rats, inhibited intestinal propulsion as tested by a charcoal meal. Such an inhibition was shown to be linearly related to the log of administered doses for both routes of administration and the two linear regressions are parallel, so that morphine was calculated to be 206 times more potent when administered i.c.v. than i.p. A dose of morphine fully active by the i.c.v. route was completely inactive when injected by the i.v., i.p., i.m. and s.c. routes. Naloxone, administered i.c.v., blocked the antipropulsive effect of morphine i.c.v. or i.p. The pA2 of naloxone versus morphine, both administered i.c.v. was determined and calculated to be 7.14 (6.76-7.62).

Relationship between morphine and etonitazene-induced working memory impairment and analgesia.

An 8-arm radial maze task was used to assess the possible role of the opiate system in the spatial memory of the rat. Increasing doses of etonitazene (0.005-0.06 mg/kg i.p.) and morphine (2.5-100 mg/kg i.p.) significantly impaired performance in the working memory components of the task. For both drugs this impairment was linearly related to the log of the administered dose, and the log-dose relationships were parallel. The regression lines calculated for each parameter for both drugs were parallel thus allowing us to calculate the potency: etonitazene proved to about 1000 times more potent than morphine in terms of correct arm entries, the number of errors and the total time taken to complete the task. Moreover, the progressive cognitive impairment produced by both opiates was closely related to an increase in analgesic effect. Pretreatment with naloxone (5 mg/kg i.p.) completely antagonised the disruptive effect of the opiates on working memory. The importance of the mu subtype opiate receptor in cognitive processes is discussed.