Nucleus accumbens dopamine and discriminated approach learning: interactive effects of 6-hydroxydopamine lesions and systemic apomorphine administration

RATIONALE: Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior. OBJECTIVES: To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior. METHODS: Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 microg/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 microl per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA. RESULTS: Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding. CONCLUSIONS: These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.     

Nucleus accumbens dopamine depletion impairs both acquisition and performance of appetitive Pavlovian approach behaviour: implications for mesoaccumbens dopamine function

The involvement of mesoaccumbens dopamine in adaptive learning and behaviour is unclear. For example, dopamine may act as a teaching signal to enable learning, or more generally modulate the behavioural expression, or selection, of an already-learned response. The present study investigated the involvement of the mesoaccumbens dopamine system in a fundamental form of learning: Pavlovian conditioning. In this case, the temporal association of a previously neutral visual stimulus and a biologically significant unconditioned stimulus (US), subsequently led to the production of the conditioned response (CR) of discriminated approach behaviour directed toward the conditioned stimulus (CS+), relative to a control (CS-) stimulus. 6-hydroxydopamine lesions of the nucleus accumbens (NAcc), leading to approximately 80% reductions in tissue dopamine, were made at varying time points in four experimental groups of rats, either before or subsequent to the acquisition of the CR. NAcc dopamine depletion produced long-term neuroadaptations in dopamine function 2 months after surgery, and profoundly impaired discriminated Pavlovian approach regardless of when the lesion was made. Thus, NAcc dopamine not only plays a role in conditioned behavioural activation, but also in making the appropriate discriminated response i.e. the direction of response. Further, acquisition lesions produced a far greater impact on discriminated approach than performance lesions. This difference in lesion-induced impairment implies that mesoaccumbens dopamine may play differential roles in the learning and performance of preparatory Pavlovian conditioning.     

移植肾功能延迟恢复的护理体会

1临床资料我院1997-11/2004-11共行肾移植562(男386,女176)例,期中87例患者出现移植肾功能延迟恢复(DGF),男性58例,女性29例,年龄16～62(平均38.5)岁.术后常规服免疫抑制剂:环孢素,强的松,骁悉.发生DGF最早术后第4日,最晚20 d,均采用综合治疗措施,纠正水、电解质紊乱,控制血压,预防感染等,同时对不同原因引起的DGF采用相应的治疗、护理.85例患者均在术后3wk左右肾功能恢复,2例因并发症死亡.     

Metabolic effects of growth hormone treatment: an early predictor of growth response?

Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months.     

Open label, multi-centre phase II study of raltitrexed (`Tomudex') in patients with inoperable squamous-cell carcinoma of head and neck

Background:Raltitrexed (`Tomudex') is a folate based inhibitorof thymidylate synthase which has been registered in Europe and Australia forthe treatment of advanced colorectal cancer. In a European phase I trial ofraltitrexed anti-tumour activity was seen in two patients with head and neckcancer, prompting the current study. Patients and methods:From November 1996 to December 1998, 24patients with metastatic or recurrent squamous-cell carcinoma of the head andneck from 7 Australian centres received raltitrexed, 3 mg/m² givenintravenously over 15 minutes every 3 weeks, for a maximum of 6 cycles.Patients were required to be chemotherapy naïve and have measurabledisease, age >18 years, WHO performance status initially 2, nosignificant intercurrent illness or organ dysfunction and a life expectancy>12 weeks. Results:Twenty-two men and two women, median age 65 years, medianperformance status 1 were enrolled. Fifteen patients (63%) had receivedboth prior surgery and radiotherapy. In 15 patients (63%) there wasrecurrent locoregional disease only. Twelve patients (50%) received onecycle of treatment with only four patients (17%) receiving four or morecycles of treatment. No patient achieved a complete or partial response,although 5 patients experienced stable disease which lasted a median of 188days (range 61–436). The median survival for the whole group was 101days (range 20–436). Raltitrexed was generally well tolerated withminimal anti-proliferative toxicity. Conclusions:Single-agent raltitrexed does not demonstratesignificant anti-tumour response rates in patients with predominantly locallyrecurrent head and neck cancer.     

Accuracy of passive ankle joint positioning during quiet stance in young and elderly subjects

Age-related postural deficits elicit compensatory mechanisms such as ankle dorsiflexion in the elderly. To gain further insight into this problem, the ability to match an ankle angle during quiet stance was studied in 12 elderly and 12 young subjects. Following an initial single limb angular perturbation presented in the ±4° range, a subject had to return a tilt platform to level, as determined by the nonperturbed limb. Elderly subjects exhibited significant positive (0.9°) over-shoot of the level position, in contrast to young subjects who matched ankle angle with a mean error of −0.1°. The elderly group also exhibited an increase in positioning error for angular displacements in the range between −1 and +1°. The results document age-related postural changes in ankle positioning which might affect postural stability in older adults.     

Multiple myeloma: evaluation by CT

Although patients who have multiple myeloma usually have straightforward clinical symptoms and corroborative radiographs, in some instances, these patients will present atypically, with symptoms suggesting active disease but radiographs that are normal or nonspecific. We reviewed the records of 32 patients who had documented multiple myeloma and had undergone CT examinations, assessing the value of those examinations. Although CT is not indicated in all patients who have multiple myeloma, it is especially useful in patients who have bone pain and normal or nonspecific radiographs. CT provided confirmatory information in all cases in which lesions were seen on radiographs. CT also frequently demonstrated a greater extent of disease than could be appreciated on the radiographs.     

Supraacetabular insufficiency fractures

Insufficiency fractures in the supraacetabular region were identified in five women, aged 55-83 years. Factors contributing to the diminished resistance of their bones included postmenopausal osteoporosis, steroid therapy, radiation therapy, and rheumatoid arthritis. The supraacetabular fractures were seen on routine radiographs as hazy bands of sclerosis located immediately above and parallel to the acetabular roof. All five patients had additional fractures in the spine or pelvis. Supraacetabular insufficiency fractures may be an unsuspected cause of hip pain, especially in older women.