Role of dopamine in d-amphetamine-induced euphoria in normal, healthy volunteers.

The present study evaluated the role of dopamine in the euphorigenic effects of d-amphetamine in normal volunteers. d-Amphetamine (20 mg) was administered alone and after pretreatment with pimozide (4 mg), fluphenazine (3 or 6 mg), or prazosin (1 or 2 mg) in 3 separate groups of participants. Subjective effects were measured at regular intervals. It was hypothesized that pimozide and fluphenazine, but not prazosin, would attenuate the euphorigenic effects of d-amphetamine. In all studies, d-amphetamine produced robust stimulant-like effects (e.g., increased scores on measures of arousal and euphoria). Although none of the antagonists significantly attenuated subjective responses to d-amphetamine, there were trends for both dopamine antagonists to reduce some responses. Both dopamine antagonists also produced modest effects when administered alone. These findings are inconsistent with those of studies with laboratory animals, perhaps because of differing experimental conditions. Alternatively, these findings raise the possibility that separate processes mediate drug reinforcement and euphoria. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.     

Application of an elastic-plastic model to the use of small specimen strength ratio for measuring fracture toughness

Data reported by Server and Wullaert correlating specimen strength ratio with fracture toughness were analyzed with the D-BCS-HSW model. This model is based on the Dugdale model, elaborated by Bilby, Cottrell and Swinden, and extended by Heald, Spink and Worthington. The data included instrumented precracked Charpy results on HSST plate 02, as well as static, intermediate, and dynamic tests of 1 — T compact and bend specimens of SA533B-1 steel. The model relates the fracture toughness to the crack length, specimen shape and size, applied failure stress and effective flow strength. The only parameter not provided by the data is the constraint factor, M, the ratio of the effective flow strength to the yield strength. The model was fitted to the data by non-linear least squares methods by which M was determined to be approx. 2.5 for the Charpy data, and from 2.1 to 2.6 for the other specimen data. The fit is considered to be reasonably good throughout the range from linear-elastic fracture mechanics through to plastic collapse. The result for the Charpy data is considered to be as good as that for the other specimens. The determination of only one parameter is needed to establish the relationship between specimen strength ratio and fracture toughness. This relationship then applies to the entire range of fracture regimes.     

Temporal patterns of transient-evoked otoacoustic emissions in normal and impaired cochleae

The spatial distribution of outer hair cells that participate in generating transient-EOE frequency-components has been investigated in man. According to several models (e.g. Wilson (1990) Hear. Res. 2, 527-532; Zwicker (1986) J. Acoust. Soc. Am. 80, 154-162; Wilson and Kemp (Eds.), Cochlear Mechanisms, Structures, Functions and Models, Plenum Press, NY), EOEs result from interferences between broadly distributed contributions, responsible for their long frequency-dependent delay. This work presents an analysis of the temporal patterns of click- and tone-burst-EOEs in human ears when contributions to EOEs are reduced by noise-induced lesions with audiometric notches centred around 4 kHz (N = 46). Although the auditory thresholds at the frequencies of the studied EOE-components were always normal, these components exhibited drastic and predictable changes compared to normal control ears (N = 40). (1) Their temporal pattern at the highest EOE frequency fmax just below the audiometric notch appeared to be determined by the cochlear state at high frequencies (6 to 8 kHz). Either it was normal and the EOE exhibited a complicated beat-structure, or it was impaired and the time envelope of the EOE was simple. In contrast, any type of time pattern could be observed in normal ears. (2) The temporal patterns of EOEs one octave below fmax always presented many beats and short delays. The proposed interpretation is that contributions to a transient-EOE component at frequency f can come from distant basal cochlear areas, i.e. more than 1 and sometimes 1.5 octaves from the place tuned to f. Therefore, the possible relationships between transient-EOEs and tuning mechanisms which presumably involve only a small number of OHC need further investigations.     

Priming effects with drugs and other reinforcers.

Abstinent drug users often report that taking even a small amount of their previously abused drug increases their desire for the drug and can lead to a full relapse. This apparent "priming" effect of drugs has been studied in both laboratory animals and humans. In animals trained to self-administer drugs, small amounts of a previously self-administered drug readily reinstate responding. In humans, administration of a previously abused drug increases self-reported craving and desire for the drug. Priming effects also occur with other reinforcers (e.g., presentation of a food stimulus increases food-reinforced responding). This article examines the generality of priming phenomena, and it examines some of the learned or unlearned processes that underlie the effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Melanoma in pregnancy

The incidence of pregnancy complicated by melanoma of the skin, calculated from data of the Netherlands Cancer Registry, is 1 per 10,000 pregnancies. The prognosis of a melanoma is not affected by prior or subsequent pregnancy. A melanoma diagnosed during pregnancy does appear to have a more unfavourable prognosis, due not to a less favourable clinical course, but to a delay in diagnosing melanoma during pregnancy and (or) a less favourable site. When a pregnancy is complicated by malignancy, in case of a melanoma there is a higher risk of placental metastasis compared with other malignancies. In nearly 50% of the cases reported in literature of placental metastasis there was foetal involvement.