Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons

Herbal cannabis, smoked in the form of marihuana or hashish, is the most common illicit drug consumed in the Western world. In the brain, cannabinoids interact with neuronal CB1 receptors, thereby producing a marked reduction of motor activity. Here, we report that the motor depressant effect produced by the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940) is attenuated by genetic inactivation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), which is abundantly expressed in the medium spiny neurons of the striatum. Point mutation of Thr34, the protein kinase A (PKA) phosphorylation site of DARPP-32, produces a similar reduction in the effect of the CB1 agonist. In contrast, point mutation of Thr75, a site on DARPP-32 specifically phosphorylated by cyclin-dependent kinase 5, does not affect the behavioral response to CP55,940. Activation of CB1 receptors, either by an agonist or by inhibition of reuptake of endogenous cannabinoids, stimulates phosphorylation at Thr34, thereby converting DARPP-32 into an inhibitor of protein phosphatase-1. Genetic inactivation either of dopamine D2 receptors or of adenosine A2A receptors reduces the phosphorylation of DARPP-32 at Thr34 and the motor depression produced by CP55,940. Our data indicate that a considerable proportion of the psychomotor effect of cannabinoids can be accounted for by a signaling cascade in striatal projection neurons involving PKA-dependent phosphorylation of DARPP-32, achieved via modulation of dopamine D2 and adenosine A2A transmission.     

The effects of age and treatment intensity on behavioral intervention outcomes for children with autism spectrum disorders

Early intensive behavioral intervention (EIBI) has been shown to effectively remediate some cases of autism. However, few studies have evaluated the importance of various factors, such as the effect of treatment intensity on treatment outcomes, and how these outcomes vary by age.The objective of this study was to evaluate the relationship of treatment hours and participant age with the rate of learning within an early intensive behavioral intervention program. The present study evaluated treatment progress for 245 children receiving EIBI services. Regression analyses were conducted to predict treatment progress based upon the number of monthly treatment hours received and the participant's age. Each of these variables were significant predictors and accounted for considerable portions of the observed variance. Further, the younger participants showed a greater benefit from increased treatment hours when compared to older participants.These data indicate that for children between 2 and 7 years of age, there was a significant increase in new skill acquisition with increased treatment hours. Further, there was not a point of diminishing-returns.     

Late-onset rheumatoid arthritis: is pitting oedema of the hands at onset a good prognostic indicator?

This prospective study compares the clinical and radiological outcome of patients with late-onset (age 65 yr and over) rheumatoid arthritis (RA) presenting with and without pitting oedema of the hands (POH). Twenty-two patients with POH (Group 1) were compared with 81 (Group 2) without POH (median age of onset of RA-Group 1: 74.3; Group 2: 73.1; female to male. ratio-Group 1: 1.2:1; Group 2: 2.5:1). The median time between the onset of arthritis and baseline assessment was 3 months. Minimum follow-up was 1 yr (median 2.4). Outcome was defined by (1) the development of erosions of the hands, wrists or feet and (2) the number of patients in remission (clinically inactive disease on two clinic visits 3 months apart with no intervening history of inflammatory joint disease). IgM rheumatoid factor (IgM RF) was less frequent in patients with POH (Group 1:8.2%; Group 2: 43.2%, P < or = 0.05). Logistic regression analysis showed that POH at onset was independent of IgM RF in determining outcome. Patients with POH were less likely to develop erosions [odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.03, 0.89]. Although initial cross-tabulation suggested an increased frequency of remission in Group 1 (Group 1: 90.9%; Group 2: 55.5%, P = 0.02), POH was not found to be a significant predictor using the logistic regression model (OR = 7.42, 95% CI 0.84, 65.7). Patients with IgM RF were more likely to develop erosions (OR = 5.1, 95% CI 1.46, 17.67) and less likely to go into remission (OR = 0.19, 95% CI 0.06, 0.68).      

Using stimulus fading without escape extinction to increase compliance with toothbrushing in children with autism

Routine toothbrushing is an essential part of good oral hygiene. This study investigated the use of stimulus fading without escape extinction to increase compliance with toothbrushing with three children with autism spectrum disorder (ASD). A 30-step stimulus fading hierarchy was implemented; gradually increasing the proximity of the toothbrush to the child's mouth, the duration of exposure to the toothbrush, and finally the duration of toothbrushing. Results demonstrated increased compliance with clinician implemented toothbrushing and generalization to caregivers for all participants. Systematic probes, conducted throughout the intervention, eliminated approximately 50% of the stimulus fading steps for each participant, with the specific steps omitted varying across participants. This study extends the generality of stimulus fading without escape extinction to oral hygiene practices for children with ASD.     

微波治疗宫颈糜烂50例

1 临床资料宫颈糜烂患者50例,年龄22 ～50岁. 盆腔检查正常,无阴道炎症,宫颈细胞学涂片无癌细胞. 糜烂面积小于宫颈总面积的1/3为轻度糜烂10例, 1/3～2/3为中度35例,2/3以上为重度5例. 其中合并宫颈直径3.0～3.5 cm为Ⅰ度宫颈肥大4例,宫颈直径3.5～4.0 cm为Ⅱ度6例,宫颈直径＞4 cm为Ⅲ度2例. 治疗使用微波治疗仪微波输出功率30～40 W,操作时间2～6 s. 选月经干净后3～5 d取膀胱截石位,常规消毒外阴、阴道、宫颈,用窥阴器充分暴露宫颈,再次用无菌干棉球擦净宫颈分泌物,以免黏液形成假结痂,影响治疗深度.     

Ultrasonic detection of nonopaque renal calculi

Four patients with 5 nonopaque renal calculi composed of uric acid were examined by ultrasound. The calculi varied in size from a 1.5 X 1.5-cm intrapelvic stone to a staghorn calculus measuring 4 cm. All stones were satisfactorily imaged by ultrasound, allowing a diagnosis of nephrolithiasis to be made with confidence in each case. In 2 patients with poor excretion on urography, the diagnosis was not suspected prior to the ultrasound examination. The authors feel that ultrasound has great potential value in the investigation of nonopaque filling defects of the renal pelvis and in patients with urographic nonvisualization who have a high risk of uric acid lithiasis.     

Intrahepatic amebic abscesses: indications for and results of percutaneous catheter drainage

Medical therapy is standard for intrahepatic amebic abscess and generally is effective. However, we have encountered a group of patients in whom percutaneous aspiration and drainage was indicated due to uncertainty of diagnosis or clinical deterioration of the patient. Twenty such patients underwent percutaneous drainage with ultrasound or CT guidance, and each patient was cured (appropriate antibiotics were administered concomitantly). The specific indications for intervention were to differentiate pyogenic from amebic abscess, pain and imminent rupture, poor response to medical therapy, false-negative results of serologic tests, noncompliance with medical treatment, left lobe abscess, and pregnancy. Diagnosis of amebiasis from examination of the fluid was seldom possible, while findings from core biopsy of the wall of the abscess led to diagnosis in three cases. Recurrence necessitating redrainage occurred in three patients; in each, catheters were removed the same day drainage was performed. There were three minor complications. Differences from percutaneous management of pyogenic abscesses included more rapid removal of catheters (four days), more frequent use of US guidance, and more common use of the prone angled approach to avoid pleural contamination. Catheter drainage may be curative and may expedite care for problematic amebic liver abscesses in selected cases.