Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy.

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.

Sexual narcissism: a validation study.

Sexual narcissism, an egocentric pattern of sexual behavior, has recently been described in the literature and has been discovered to be associated with cluster B type personality disorders. Although the research seems to have validated sexual narcissism as a characteristic of borderline and histrionic personality disorders, it is yet to be tested with narcissistic personalities. In an effort to further explore this relationship as well as the validity of sexual narcissism, this study systematically compared a sample (ages 24-33 years) of males with narcissistic personality disorder with an adequately matched sample of males without personality disorders. As compared to the control group, narcissistic men were found to have significantly lower self-esteem, more negative attitudes toward sex, greater egocentric patterns of sexual behavior, more conservative or traditional gender-role orientation, and greater sexual preoccupation. Despite these findings, there were no significant differences between the groups on sexual depression and the narcissistic men evidenced significantly higher sexual esteem. Implications for these findings are discussed.

A pharmacological evaluation of the pull-up test for muscle relaxation in rats.

The pull-up test for muscle relaxation is described and validated. At testing, rats were evaluated for their ability to recover ('pull-up') from a fully inverted head-down position. Control animals rapidly regained position (median: 1 s). Known muscle relaxants increased latency to pull-up compared to controls. The test proved sensitive to the effects of barbiturates and benzodiazepines which produced graded dose-response functions. In general, results in the pull-up test corresponded with known potencies, with weaker muscle relaxants such as clobazam and oxazepam being less active. The test was relatively insensitive to non-benzodiazepine compounds (e.g., haloperidol, etomidate, morphine, fentanyl and risperidone) producing cataleptic, catatonic, neuroleptic, analgesic, sedative or hypnotic effects. In terms of ED50 values for barbiturates and benzodiazepines, the pull-up test correlated significantly with ED50s from the rotarod test, the antipentylenetetrazol test, ataxia in rats and muscle relaxation in cats. It was concluded that the pull-up test was relatively specific for muscle relaxation and provided a simple alternative to more time-consuming or equipment-intensive tests.

Direct evidence for mediation of an anticonflict effect of baclofen by GABAb receptors.

The present article reports an experiment on the effects of baclofen (0, 0.5, 1.0, and 2.0 mg/kg) on punished drinking in rats and the modification of these by delta-amino-n-valeric acid (DANVA) (0 and 10.0 mg/kg). Baclofen significantly enhanced punished drinking and this increase was abolished by DANVA, which had no intrinsic anxiogenic activity. It is concluded that GABAb receptors probably mediate this effect of baclofen and that such receptors may be a potential site of anxiolytic drug action.

Thermal homeostasis in pregnant rats during heat stress.

Rats exposed to inescapable heat stress maintained a controlled hyperthermia while increasing heat loss by cutaneous vasodilatation and by grooming behavior. In nonpregnant rats, the evaporation of saliva groomed onto the body surfaces increased exponentially as a function of ambient temperature above 36 degrees C. This was associated with a decrease in the body temperature threshold for salivary secretion from the submaxillary gland, which then began at approximately the same body temperature as cutaneous vasodilatation. In addition, the pregnant rats maintained a lower level of controlled hyperthermia during heat stress than did nonpregnant rats. This appeared to result from a decreased production of metabolic heat, reduced insulation on the ventral surface, and an increased motivation to keep cool during heat stress. These changes met the increased need for thermolysis during pregnancy and provided for thermal homeostasis both in the pregnant rat and in the unborn fetuses.

Spontaneous recovery from nondepolarizing neuromuscular blockade: correlation between clinical and evoked responses.

The effects of nondepolarizing muscle relaxants were allowed to wear off spontaneously in 10 ASA class III and IV patients following major surgery. Neuromuscular and respiratory function were followed by clinical testing and by evoked muscle responses using a train of 4 (TOF) supramaximal stimuli. At a TOF of 70 percent (range 62 to 78%), all patients sustained eye-opening, hand-grasp, and tongue-protrusion, while 9/10 sustained head-lift. Vital capacity (VC) averaged 17 ml/kg when the TOF reached 70 percent. The increase in VC correlated with the increase in TOF (r = 0.88). There was no correlation between inspiratory force (IF) and TOF, but all patients achieved an IF equal to or greater than -22 cm H2O at 70 percent. Thus, TOF correlates well with clinical signs of neuromuscular and respiratory recovery in this group of patients and complements earlier studies in healthy anesthetized patients and nonmedicated volunteers.

Radioimmunoassay of antidiuretic hormone during morphine anaesthesia.

The effect of morphine anaesthesia on plasma antidiuretic hormone levels was studied in seven adult patients. Measurements of ADH showed no significant change with morphine and 50 per cent nitrous oxide. Significant elevation occurred with surgical stimulation as previously reported. Changes in urine flow with high doses of morphine are then not ADH related.