Mesolimbic dopamine and its control of locomotor activity in rats: differences in pharmacology and light/dark periodicity between the olfactory tubercle and the nucleus accumbens

To compare the functions of the lateral olfactory tubercle (OT) and the medial nucleus accumbens (ACC), dopamine (DA), (3,4-dihydroxyphenylimino)-2-imidazoline (DPI), and ergometrine were injected into the brain of rats familiarized with the experimental cage in which locomotor activity was assessed. In all tests a volume of 0.5 l per side was used. Both DA (1–10 g) and apomorphine (1–10 g) increased locomotor activity when injected into the OT; similar injections into the ACC produced inconsistent effects. The OT effects were short-lasting, dose-dependent and antagonized by haloperidol (0.5–2.5 g) in a dose-dependent manner. DPI (1–10 g) too produced an increase when injected into the OT; this response was long-lasting, dose-dependent and potentiated by ergometrine (0.1–1.0 g). Ergometrine (0.1–1.0 g) dose-dependently increased activity over a period of 200 min in ACC and OT rats, although the response in OT rats was much smaller than that in ACC rats. Only the ergometrine response in ACC rats was dose-dependently suppressed by DPI (1–10 g). ACC rats tested during the light period showed a weak stimulatory response to ergometrine in comparison with ACC rats tested during the dark period; OT rats showed reversed light/dark periodicity. Thus, OT rats significantly differed from ACC rats with respect to locomotor responses to dopaminergic agents, their pharmacological profile and their light/dark periodicity. Evidence is provided that the lateral tuberculum, but not the medial accumbens, is responsible for the stimulatory effect of dopamine and related compounds.The results were presented during the 14th C.I.N.P. Congress (Collegium International Neuro-Psychopharmacologicum), held at Florence (Italy), June 19–23, 1984     

急性重度毒蕈中毒性肝炎抢救成功1例

1　病例报告　男 ,16岁 .误食毒蕈后出现恶心 ,呕吐伴有腹痛、腹泻 4d,每日大便 4～ 12次 ,为稀水便 ,有心慌、气短、发热 ,在当地医院以“毒蕈中毒”救治 ,症状无缓解 ,为进一步治疗于 2 0 0 0 - 0 8- 31转入我院 .查体 :T37.8℃ ,P110次·min-1 ,R18次·min-1 ,BP14/ 9k Pa.全身皮肤黄染 ,巩膜重度黄染 ,心肺无阳性体征 .腹平坦 ,上腹部有压痛 ,肌紧张及反跳痛 ,肝脾未触及 ,肝区有叩击痛 ,移动性浊音阳性 .入院后患者出现烦躁 ,意识不清 ,心率时快时慢 ,血压不稳定 .肝功 :T- BIL 2 5 4.1μmol· L-1 ,D- BIL 16 9.5 μmol· L-1 …     

Relationship between memory strategies and motor symptoms in Parkinson's disease

Patients with Parkinson's disease(PD) show a serious decrease in performance on tasks which lack explicit guidelines and which necessitate the subject to develop his or her own strategy. Using the California Verbal Learning Task(CVLT) we have found evidence that this phenomenon becomes also manifest in learning and memory. The goal of the present study on PD was to investigate whether or not there is an intrinsic relationship between PD-specific deviant learning characteristics and the severity of motor symptomatology. The results show, as expected, a significant correlation between the severity of bradykinetic/hypokinetic symptoms and the serial clustering gradient of the CVLT: the more bradykinetic PD patients (n = 48) were, the more they were dependent on the externally guided serial learning strategy. The findings are discussed in the context of our hypothesis that the actual deficit in patients with PD is a deficient processing of ambiguous internal cues.     

Sub-chronic administration of the dopamine D1 antagonist SKF 83959 in bilaterally MPTP-treated rhesus monkeys: stable therapeutic effects and wearing-off dyskinesia

  Rationale: SKF 83959 acts as a D₁ antagonist in vitro but has been claimed to induce anti-parkinsonian effects after acute administration in MPTP-treated marmosets. Objective: The aim of the present study was to evaluate the therapeutic and undesired effects of sub-chronic administration of SKF 83959 in bilaterally MPTP-treated rhesus monkeys and to compare these effects with the effects of l-dopa and the dopamine agonist SKF 82958. Methods: MPTP was given in the left carotid artery (2.5 mg) and 6 weeks later, the right carotid artery (1.25 mg). The monkeys (n=4) had previously been treated chronically with l-dopa (22 days, 10 mg/kg) and SKF 82958 (22 days, 1 mg/kg). Three months after the last administration of SKF 82958, SKF 83959 was given in a dose of 0.5 mg/kg from day 1 to day 15 and in a dose of 1.0 mg/kg from day 16 to day 18. Results:SKF 83959 increased goal-directed limb movements in all animals, including those unresponsive to l-dopa. This therapeutic effect did not diminish during treatment. With respect to body displacement and undesired effects, a large variation in the response to SKF 83959 was found: a large increase in body displacement co-occurred with oro-facial dyskinesia (n=2), whereas a small increase in body displacement co-occurred with dystonia (n=2). In contrast to the undesired effects of l-dopa, the dyskinetic effects of SKF 83959 were primarily limited to the first treatment day. Unlike l-dopa and SKF 82958, SKF 83959 did not induce epileptoid behaviour. Conclusion: Sub-chronic administration of SKF 83959 induced both clear-cut therapeutic effects that remained stable in time, and a limited number of dyskinetic effects that wore off during the treatment. The dopamine D₁ antagonist SKF 83959 may be considered as an alternative treatment in Parkinson’s disease, especially in those patients who do not respond to l-dopa. Received: 4 March 1999 / Final version: 5 May 1999     

What is the difference between squamous cell carcinoma and adenocarcinoma of the cervix? A matched case–control study

The objective of this study was to investigate the efficacy of treatment strategies in patients with adenocarcinoma (AC) of the cervix and compare it with those with squamous cell carcinoma (SCC) of the cervix. Women with FIGO (1994) stage IB1 AC, especially pathologic tumor size of 2-4 cm, treated with class III hysterectomy, were compared with those with SCC treated with comparable strategy in a case-controlled study. Eighty patients (20 cases, 60 controls) were analyzed. Lymphvascular space invasion (P = 0.01) and lymph node metastasis (P = 0.07) were more frequent in patients with SCC than in those with AC. However, there was no significant difference in depth of stromal invasion (P = 0.51) and invasion of the parametrium (P = 0.44) between two groups. And there was also no statistically significant difference in disease-free survival (P = 0.86) and overall survival (P = 0.89) between two groups. Primary radical surgery followed by adjuvant therapy, same as for SCC, would be acceptable for AC with pathologic tumor size of 2-4 cm. Although it was difficult to determine whether AC recurred more systemically, more effective treatment strategies than those currently available for AC should be considered to reduce the systemic recurrence.     

Resistance to tyrosine kinase inhibitors: calling on extra forces.

Over the past 5 years, small molecule tyrosine kinase inhibitors have been successfully introduced as new cancer therapeutics. The pioneering work with the ABL inhibitor imatinib (Glivec, Gleevec) was rapidly extended to other types of leukemias as well as solid tumors, which stimulated the development of a variety of new tyrosine kinase inhibitors. Unfortunately, oncogenic tyrosine kinases seem to have little problem to develop resistance to these inhibitors, and there is good evidence that this is not limited to imatinib, but also occurs with other inhibitors, such as FLT3 and EGFR inhibitors. Based on studies with imatinib, mutation and amplification of the target kinase seem to be the most important mechanisms for the development of resistance, but these mechanisms alone cannot explain all cases of resistance. A better understanding of the resistance mechanisms will be required to design improved treatment strategies in the future. In this review, we summarize the current insights in the different mechanisms of resistance to small molecule tyrosine kinase inhibitors, and discuss future improvements that might limit or even overcome resistance.     

Tear of the distal biceps branchii tendon: A new method of ultrasound evaluation

Tear of the distal biceps brachii tendon is an uncommon injury. Ultrasound evaluation of the distal tendon using an anterior approach is often difficult because of technical factors. We describe a new method of ultrasound evaluation of the distal biceps tendon insertion. This involves a posterior approach with the forearm pronated. With pronation of the forearm, the radial tuberosity faces posteriorly, bringing the distal biceps tendon insertion into view. A surgically proven case of distal biceps tendon tear is presented to illustrate our technique.     

Achilles tendinopathy after treatment with fluoroquinolone

Fluoroquinolone antibiotic therapy is a recognized but poorly understood cause for Achilles tendinopathy. We report here a patient who developed bilateral partial Achilles tendon tears as a result of fluoroquinolone therapy. Ultrasound and MRI were both useful in identifying and distinguishing between Achilles tendinosis and tendon rupture. The current published literature on this problem was also reviewed.