PO-41 - Rivaroxaban is effective therapy for high risk cancer patients with venous thromboembolic disease.

INTRODUCTION: The standard of care for cancer associated venous thromboembolism (VTE) is generally accepted to be at least six months of therapeutic doses of low molecular weight heparin (LMWH). After six months it is recommended that therapy be continued but no studies have evaluated treatment in this period. Rivaroxaban is a potentially effective therapy given cancer patients were enrolled in the EINSTEIN trial with acceptable safety and efficacy but details on these patients is lacking. AIM: To determine the safety and efficacy of rivaroxaban for the treatment of cancer associated VTE. MATERIALS AND METHODS: We performed a retrospective chart review of all cancer patients seen in our thrombosis program and enrolled patients seen between January 2012 and April 2015. Complete patient identification was accomplished through our hospital data warehouse. We recorded all relevant demographics. Initial diagnoses were all confirmed with objective imaging tests according to standard definitions. Major bleeds, using the ISTH definition, and recurrent VTE events were adjudicated by at least two observers. RESULTS: 237 active cancer patients received treatment with rivaroxaban; 65 (27%) were initiated on rivaroxaban, 30 (12.6%) started between day 8 and 2 months, 75 (32%) started therapy between day 8 and the 6 month point and 97 (41%) started therapy at 6 months or beyond. 26 patients were put on rivaroxaban after failing LMWH. The average duration of rivaroxaban therapy was 297 days; The average age of patients was 61 (SD±13); 41% of patients were male, 59% were female. 47% of patients had metastatic cancer. Of the 65 patients who were initiated on rivaroxaban 24 (37%) had metastatic cancer. Overall 3.8% of patients recurred while on rivaroxaban therapy with no deaths due to PE, and 3 patients had major hemorrhage with 2 deaths. Of the 9 patients who recurred on rivaroxaban, 3 of them were initiated on rivaroxaban, 3 of them were started 8 days-6 months, and 3 of them started after 6 months. The median number of days from initiation of rivaroxaban to VTE recurrence was 113. 26 patients received rivaroxaban after a recurrent event on therapeutic doses of LMWH, none recurred. Of the 65 patients who were initiated on rivaroxaban 3 recurred and of the 97 patients who were started on rivaroxaban after 6 months three recurred 0.580). All patients were treated on an outpatient basis. CONCLUSIONS: Recurrence and major bleeding events on rivaroxaban were low despite the fact almost half the patients had metastatic disease. Rivaroxaban can be considered acceptable therapy for the treatment of cancer associated with venous thromboembolic disease.

Baseline imaging after therapy for unprovoked venous thromboembolism: a randomized controlled comparison of baseline imaging for diagnosis of suspected recurrence.

BACKGROUND: After a first unprovoked venous thromboembolism (VTE), many patients have residual pulmonary and/or lower limb vascular obstruction following completion of short-term anticoagulation. Residual vascular obstruction may complicate the diagnosis of recurrent VTE. Whether baseline imaging, conducted after completion of anticoagulation, helps in interpreting diagnostic testing in patients who subsequently have suspected recurrent VTE is unknown. STUDY DESIGN: The REVERSE study is a cohort study whose primary aim was to derive a clinical decision rule to guide the duration of anticoagulation after a first unprovoked VTE. All patients underwent baseline imaging after completing 5-7 months of anticoagulant therapy. We performed a post hoc randomized controlled comparison among 121 patients investigated for a suspected recurrent VTE during follow-up: the decision on recurrent VTE with or without baseline imaging was made available to two independent adjudicators. RESULTS: The proportion of patients not classifiable for recurrent VTE was statistically significantly higher in the group with no baseline imaging than in the group with baseline imaging: one in five as compared with one in 25. The interobserver agreement between the two adjudicators was better in the group with baseline imaging than in the group with no baseline imaging: κ-values were 0.78 and 0.54, respectively. CONCLUSIONS: In patients with a first unprovoked VTE, baseline imaging at completion of anticoagulant therapy helps in interpreting diagnostic tests performed in cases of suspected recurrent VTE.

Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

Pre-operative autologous donation for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Public concerns regarding the safety of transfused blood have prompted re-consideration of the indications for the transfusion of allogeneic red cells (blood from an unrelated donor), and a range of techniques designed to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of pre-operative autologous blood donation (PAD) in reducing the need for peri-operative allogeneic red blood cell (RBC) transfusion. SEARCH STRATEGY: Articles were identified by: computer searches of OVID MEDLINE, EMBASE, and Current Contents (to March 2001) and web sites of international health technology assessment agencies (to January 2001). References in the identified trials were checked and authors contacted to identify additional studies. SELECTION CRITERIA: Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to PAD, or to a control group who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al (1995) and Jadad et al (1996). The principle outcomes were: the number of patients exposed to allogeneic red blood cells, and the amount of blood transfused. Other clinical outcomes are detailed in the review. MAIN RESULTS: Overall PAD reduced the risk of receiving an allogeneic blood transfusion by a relative 63% (RR=0.37: 95%CI:0.26,0.54). The absolute reduction in risk of allogeneic transfusion was 43.8% (RD=-0.438: 95%CI: -0.607,-0.268). In contrast the results show that the risk of receiving any blood transfusion (allogeneic and/or autologous) is actually increased by pre-operative autologous blood donation (RR=1.29: 95%CI: 1.12,1.48). Trials were unblinded and allocation concealment was not described in 87.5% of the trials. REVIEWER'S CONCLUSIONS: Although the trials of PAD showed a reduction in the need for allogeneic blood the methodological quality of the trials was poor and the overall transfusion rates (allogeneic and/or autologous) in these trials were high, and were increased by recruitment into the PAD arms of the trials. This raises questions about the true benefit of PAD. In the absence of large, high quality trials using clinical endpoints, it is not possible to say whether the benefits of PAD outweigh the harms.

Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer.

BACKGROUND: The limitations of the current diagnostic standard, ventilation-perfusion lung scanning, complicate the management of patients with suspected pulmonary embolism. We previously demonstrated that determining the pretest probability can assist with management and that the high negative predictive value of certain D -dimer assays may simplify the diagnostic process. OBJECTIVE: To determine the safety of using a simple clinical model combined with D -dimer assay to manage patients presenting to the emergency department with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Emergency departments at four tertiary care hospitals in Canada. PATIENTS: 930 consecutive patients with suspected pulmonary embolism. INTERVENTIONS: Physicians first used a clinical model to determine patients' pretest probability of pulmonary embolism and then performed a D -dimer test. Patients with low pretest probability and a negative D -dimer result had no further tests and were considered to have a diagnosis of pulmonary embolism excluded. All other patients underwent ventilation-perfusion lung scanning. If the scan was nondiagnostic, bilateral deep venous ultrasonography was done. Whether further testing (by serial ultrasonography or angiography) was done depended on the patients' pretest probability and the lung scanning results. MEASUREMENTS: Patients received a diagnosis of pulmonary embolism if they had a high-probability ventilation-perfusion scan, an abnormal result on ultrasonography or pulmonary angiography, or a venous thromboembolic event during follow-up. Patients for whom the diagnosis was considered excluded were followed up for 3 months for the development of thromboembolic events. RESULTS: The pretest probability of pulmonary embolism was low, moderate, and high in 527, 339, and 64 patients (1.3%, 16.2%, and 37.5% had pulmonary embolism), respectively. Of 849 patients in whom a diagnosis of pulmonary-embolism had initially been excluded, 5 (0.6% [95% CI, 0.2% to 1.4%]) developed pulmonary embolism or deep venous thrombosis during follow-up. However, 4 of these patients had not undergone the proper diagnostic testing protocol. In 7 of the patients who received a diagnosis of pulmonary embolism, the physician had performed more diagnostic tests than were called for by the algorithm. In 759 of the 849 patients in whom pulmonary embolism was not found on initial evaluation, the diagnostic protocol was followed correctly. Only 1 (0.1% [CI, 0.0% to 0.7%]) of these 759 patients developed thromboembolic events during follow-up. Of the 437 patients with a negative D -dimer result and low clinical probability, only 1 developed pulmonary embolism during follow-up; thus, the negative predictive value for the combined strategy of using the clinical model with D -dimer testing in these patients was 99.5% (CI, 99.1% to 100%). CONCLUSION: Managing patients for suspected pulmonary embolism on the basis of pretest probability and D -dimer result is safe and decreases the need for diagnostic imaging.

Mechanisms underlying the absence of the pubertal shift in the playful defense of female rats.

Due to the action of testicular hormones in the perinatal period, juvenile male rats engage in more play fighting than juvenile females. Also, following puberty, males, but not females, switch to using adultlike defensive tactics more frequently during play. This change in play is also due to the action of testicular hormones perinatally. In this study, two experiments were conducted to determine if the pubertal transition in defense could be induced in females. For Experiment 1, male and female cagemates were tested before and after puberty with familiar and unfamiliar partners. Even when playfully interacting with subadult males, females did not increase the use of the adultlike defensive tactics. For Experiment 2, neonatal females were either injected with testosterone propionate (TP) or ovariectomized (OVX), and again tested before and after puberty. While the TP-treated females had higher frequencies of play fighting, they did not change their pattern of defense following puberty. The OVX females exhibited the lower frequency of play fighting typical of females, but changed their pattern of defense with increased age. Thus, it appears that the pattern of pubertal change in playful defense typical of males is inhibited by ovarian hormones. The mechanisms by which ovarian hormones could exert this effect on developing females are discussed.

Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection.

BACKGROUND: The outpatient treatment of patients with deep vein thrombosis and pulmonary embolism using low-molecular-weight heparin has the potential to reduce health care costs, but it is unclear if most patients with deep vein thrombosis and pulmonary embolism can be treated as outpatients. In the published studies, more than 50% of patients were excluded from outpatient treatment for reasons such as comorbid conditions, short life expectancy, concomitant pulmonary embolism, and previous deep vein thrombosis, and many patients were not treated entirely at home. We sought to determine if expanding patient eligibility for the outpatient treatment of deep vein thrombosis and pulmonary embolism affects the safety and effectiveness of the treatment, and to determine if patient self-injection compared with injections administered by a homecare nurse affected these outcomes. PATIENTS AND METHODS: We treated as outpatients all patients with deep vein thrombosis and pulmonary embolism, except for those with massive pulmonary embolism, high risk for major bleeding or an active bleed, phlegmasia, and patients hospitalized for reasons that prevented discharge. We compared 2 models of outpatient care to determine feasibility, safety, and efficacy. Both models involved nurse managers who provided daily patient contact and ongoing treatment; however, in one model the patients were taught to inject themselves and in the other model homecare nurses administered the injections. We expanded the population of patients eligible for outpatient treatment by including many patients not treated at home in previous studies. Most patients in our study were treated with dalteparin sodium, 200 U/kg every 24 hours, for a minimum of 5 days. Therapy with warfarin sodium was started on the day of diagnosis or the following day. Patients were followed up for 3 months to determine rates of recurrent venous thromboembolism, bleeding, and death. RESULTS: In this study, 194 (83%) of 233 consecutive patients were deemed eligible and treated as outpatients. Of the 39 patients who did not receive home therapy, 20 had concomitant medical problems responsible for their admission or were already inpatients, 6 had massive pulmonary embolism, 6 refused to pay for the dalteparin therapy, 4 had active bleeding, and 3 had phlegmasia cerulea dolens, which required treatment with intravenous narcotics for pain control. More than 184 (95%) of the 194 patients were treated entirely at home. There was no significant difference (P>.99) in the rate of recurrent venous thromboembolic events between the patients who were injected by homecare nurses (3/95 [3.2%]) and those who injected themselves (4/99 [4.0%]). Combining the 2 models, the overall recurrent event rate was 3.6% (95% confidence interval, 1.5%-7.4%). Similarly, there were no significant differences in rates of major hemorrhage (2/95 vs 2/99; P>.99), minor hemorrhage (8/95 vs 2/99; P = .06), and death (6/95 vs 8/99; P = .63). The overall rate of major hemorrhage was 2.0% (95% confidence interval, 0.6%-5.2%). CONCLUSIONS: We demonstrate that more than 80% of patients at our tertiary care hospital could be treated at home using 1 of the 2 models of care we describe. Our results demonstrate that patients can safely and effectively perform home self-injection under the supervision of a hospital-based nurse. Injections at home by a homecare nurse are similarly effective. Our overall rates of recurrent venous thromboembolism, bleeding, and death are at least as favorable as those previously reported despite using 1 dose per day of dalteparin for most patients.

Age, experience and the changing brain.

In this review, various aspects of how environmental experience effects the structure of the cortex at different times in the age of the animal are summarized. The interactions of brain injury and sex on the age-dependent plastic changes in the cortex are also considered. Finally, we have attempted to reach some general conclusions that describe the effects of age, experience, sex, and injury on the cortex.

Preoperative autologous donation decreases allogeneic transfusion but increases exposure to all red blood cell transfusion: results of a meta-analysis. International Study of Perioperative Transfusion (ISPOT) Investigators.

BACKGROUND: Concern about risks associated with allogeneic red blood cell transfusion has led to interest in methods of decreasing patient exposure to perioperative transfusion. OBJECTIVE: To perform a meta-analysis to determine the degree to which predonation of autologous blood reduces patients' exposure to allogeneic blood and all transfusions of red blood cells (allogeneic or autologous). METHODS: We searched MEDLINE, EMBASE, bibliographies, annual reports, press releases, newsletters from organizations with interests in the blood system, and personal files for randomized studies and concurrent control cohort studies in which the control groups were patients excluded for nonmedical reasons. RESULTS: Patients who predonated autologous blood were less likely to receive allogeneic blood in the 6 randomized studies (n = 933) (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.08-0.32) and in the 9 cohort studies (n = 2351) (OR, 0.19; 95% CI, 0.14-0.26). However, autologous donors were more likely to undergo transfusion with allogeneic and/or autologous blood (for randomized studies: OR, 3.03; 95% CI, 1.70-5.39 and for cohort studies: OR, 12.32; 95% CI, 5.90-25.40). Studies that reported use of transfusion protocols found less benefit with preoperative autologous donation, although the difference was not statistically significant. CONCLUSIONS: Preoperative autologous donation of blood decreases exposure to allogeneic blood but increases exposure to any transfusion (allogeneic and/or autologous). There is a direct relationship between the transfusion rate in the control group and the benefit derived from preoperative autologous donation. This suggests that other methods of decreasing blood transfusion, such as surgical technique and transfusion protocols, may be as important as preoperative autologous donation of blood.

Sex differences in the effects of frontal cortex injury: role of differential hormonal experience in early development.

The extent to which sex differences in the behavioral effects of frontal injury in the adult rat can be attributed to differential exposure to testosterone (T) during development was investigated. The effects of these factors on brain weight and relative brain size were also examined. At birth, males were gonadectomized (GDX) or not and females were given T or oil injections. In adulthood, all animals were GDX or sham-operated and received either bilateral aspiration lesions of the medial frontal cortex or a sham operation. Rats were tested on the Morris water maze task, the radial arm maze (RAM), and the landmark water task. The effects of frontal injury on performance of the Morris water maze task were greater in rats not exposed to T at birth, there was no effect of neonatal T exposure on performance on the RAM, and on the landmark water task there was a complicated interaction of sex and neonatal T exposure in rats with frontal injury.

The postpubertal change in the playful defense of male rats depends upon neonatal exposure to gonadal hormones.

The pattern of playful defense used during play fighting by male rats (Rattus norvegicus) castrated at birth was compared to that of sham-operated and untreated controls during the juvenile phase and after puberty. The neonatal castrates failed to exhibit the age-related changes in playful defense present in intact male rats of the same age. Following puberty, control rats, but not neonatal castrates, switched from juvenile to more adult-typical defensive tactics. That the neonatal castrations were effective was independently shown by the animals' failure to exhibit the asymmetries in weight and play behavior indicative of dominance-subordinance relationships present in normal adult males. A previous study found that castration following weaning did not prevent the pubertal change in playful defense, but did block the formation of dominance-subordinance relationships. Therefore, it appears that the age-related shift in playful defense is a feature of the development of play fighting in males that is likely preprogrammed by gonadal hormone exposure in the perinatal period.

Unilateral lesions of the forelimb area of rat motor cortex: lack of evidence for use-dependent neural growth in the undamaged hemisphere.

Unilateral lesions of the forelimb area of the motor cortex have been reported to produce enhanced dendritic outgrowth in the undamaged hemisphere in response to the behavioral asymmetry produced by the lesions (e.g. Jones, T.A. and Schallert, T., Use-dependent growth of pyramidal neurons after neocortical damage, J. Neurosci, 14 (1994) 2140-2152). We attempted to replicate this result and to determine if there were sex differences in cortical plasticity using the Jones and Schallert model. Animals were given either unilateral aspiration or electrolytic lesions of the forelimb area of the motor cortex or a sham operation. Use of the forelimb ipsilateral to the lesion for postural support was assessed pre- and postsurgery. Eighteen days after surgery the animals were sacrificed. and the brains processed for Golgi-Cox staining or a series of other stains for acetylcholine, astrocytes (glial fibrillary acidic protein), and microglia (OX-42). Although the lesions produced significant behavioral asymmetry and enhanced glial response on the lesioned side, there was little evidence for use-dependent neural growth in the undamaged hemisphere in either sex.

Diagnosis of deep vein thrombosis.

Deep vein thrombosis (DVT) is an important, treatable disease that can be diagnosed by noninvasive imaging procedures. Ultrasound is the most accurate and readily available of these modalities but it still has limitations. False positive results occur in up 6% of patients, and calf DVT is not readily detected; thus serial ultrasonography is recommended in order to detect extension of a calf DVT. However, this results in many patients needlessly returning for a repeat assessment. A recently developed clinical model has the potential to identify false positive ultrasound results and to select patients who do not require serial testing. Certain rapidly performed D-dimer assays have similar potential but have not been evaluated in management strategies. In the subgroup of patients with suspected recurrent DVT and asymptomatic patients at high risk for DVT, ultrasonography and impedance plethysmography are less accurate, however, the clinical implications of this are unknown.

Effect of prepubertal ovariectomy on amphetamine-induced locomotor activity in adult female rats.

Adult female rats show greater behavioral activation in response to both acute and repeated injections of amphetamine (AMPH) than adult male rats. The present experiments investigated whether life-long exposure to ovarian hormones in females contributes to their enhanced responsiveness to AMPH as adults and whether this effect depends on exposure to testosterone (T) in the neonatal period. In Experiment 1, female rats were ovariectomized either prior to puberty (EARLY) or in adulthood (ADULT). Locomotor activity in response to either 1.5 mg/kg AMPH or the saline vehicle was measured for 2 hr every third day on five occasions. On the sixth occasion all animals received 0.75 mg/kg AMPH in a test for sensitization. Each animal received either 5.0 micrograms estradiol benzoate (EB) or the oil vehicle (OIL), 30-35 min prior to each session. Experiment 2 was similar except that all animals were treated with T at birth. In Experiment 1, during the repeated treatment period, group EARLY had lower AMPH-induced activity scores than group ADULT, in both OIL and EB conditions. EB-treated rats had higher levels of AMPH-induced activity and showed greater changes in activity over days of testing than OIL-treated rats, regardless of time of ovariectomy. Animals previously exposed to AMPH showed higher levels of activity on the test for sensitization than animals receiving the drug for the first time, but this effect did not vary as a function of hormone condition or time of ovariectomy. Exposure of females to T at birth reduced responsiveness to AMPH and EB in adulthood, and ovariectomy prior to puberty had little effect in these animals.

Six differences in the locomotor-activating effects of amphetamine: role of circulating testosterone in adulthood.

The effects of circulating testosterone (T) on sex differences in locomotor activity elicited by both acute and repeated amphetamine (AMPH) administration were evaluated in adult rats. Male and female rats were gonadectomized in adulthood and implanted with Silastic capsules containing either T or cholesterol (CHOL). In the preexposure period, locomotor activity in response to IP injections of either AMPH (1.5 or 1.3 mg/kg) or saline (1.0 ml/kg) was measured for 2 h, every third day on five occasions. In a subsequent test for sensitization, all animals received AMPH (0.75 or 0.65 mg/kg). Results indicate that regardless of the presence of circulating T, females showed higher levels of activity in response to AMPH than males. In male animals, T suppressed AMPH-induced activity on the first day of the preexposure period, but this effect was lost with repeated testing. In female animals, T enhanced AMPH-induced activity during the first hour of testing. The presence of circulating T did not influence the degree of sensitization in either sex as determined by the difference between AMPH preexposed and SAL preexposed animals on the test day for sensitization.

Sex differences in amphetamine-induced locomotor activity in adult rats: role of testosterone exposure in the neonatal period.

The present studies assessed the extent to which adult sex differences in responsiveness to both acute and repeated amphetamine (AMPH) treatment can be attributed to differential exposure to testosterone (T) during the early critical period for sexual differentiation. At birth, male pups were sham-operated or gonadectomized, whereas female pups were given T or an oil injection. In adulthood, all animals were gonadectomized or sham-operated. Locomotor activity in response to either 1.5 mg/kg AMPH (IP) or the saline vehicle was measured for 2 h every third day, on five occasions. On the sixth occasion, all animals received 0.75 mg/kg AMPH (IP) in a test for sensitization. In Experiment 1, animals were tested in the absence of circulating gonadal hormones, whereas in Experiment 2, all animals received 5.0 micrograms estradiol benzoate (SC), 30-35 min prior to each behavioral test. Results indicate that neonatal exposure to T suppresses responsiveness to AMPH in adulthood. The differences between neonatal T-exposure groups were magnified in the presence of circulating estradiol. The fact that female animals were more responsive to AMPH regardless of neonatal T exposure suggests that lifetime exposure to estradiol alters responsiveness to this hormone, and to AMPH, in adult animals and/or that exposure to T both pre- and postnatally is necessary for the full suppression of responsiveness seen in adult male animals.

Mapping the substrate for brain stimulation reward by means of current-number trade-off functions.

In previous studies using moveable electrodes to map the substrate for brain stimulation reward, reward effectiveness was estimated by varying either the current or the number of pulses per train. The resulting relationship between reward effectiveness and stimulation site is independent of the fixed parameter only if the current-number trade-off functions (TOFs) for all sites are parallel. This assumption was tested in the present experiment. Movement of an electrode through or near the ventral tegmental area did not always shift the TOFs in a parallel manner and sometimes caused them to intersect. To describe such effects, a current-number TOF must be obtained at each site in lieu of a single estimate of the required stimulation strength. Across-site changes in the parameters of these TOFs are interpreted in terms of differences in the density, excitability, or postsynaptic impact of the directly stimulated reward neurons.

Contributions of taste factors and gender to opioid preference in C57BL and DBA mice.

C57BL/6J and DBA/2J mouse strains have been characterized as morphine preferrers and avoiders, respectively (Horowitz et al. 1977). Previously, sweetened morphine solutions were presented with a water alternative, primarily with male subjects. Because sweetness may affect the endogenous opioid system and rodents have shown strain and sex differences in taste preferences, this study looked for strain- and gender-related taste preferences that might have affected opiate consumption. Preference for sweetened and unsweetened morphine and etonitazene was compared across gender and strain. In all choice tests, the control was a similar tasting quinine sulphate solution. Under these conditions, C57BL/6J mice continued to show strong preference for morphine. However, DBA/2J mice drank approximately equal amounts of morphine and quinine solutions, rather than avoiding morphine as when water was the alternative. Both strains appeared surprisingly indifferent to the synthetic opioid etonitazene, compared because it is potent at concentrations having barely perceptible bitterness. This raises the possibility of unexpected differences in post-ingestional effects between morphine and etonitazene. Contrary to reports of gender differences in sweet preference in rats, none were found in either strain of mouse. Neither were there any significant sex differences in opiate preference in either strain. C57 mice preferred sweetness more than did DBA mice.

Practical applications of the Quantimet 720, an image analysing computer, in the field of investigative dermatology.

Image analysing computers can perform quantitative measurements of epidermal thickness, sebaceous gland volume, and labelling indices of epidermis easily, rapidly and automatically. All these parameters are extremely important in investigative dermatology and this paper describes how they are measured using the Quantimet 720.