Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

The impact of obesity on female reproductive function

Obesity may be described as the new worldwide epidemic, and its serious impact on morbidity and mortality are well known. As more and more women become obese, the reproductive problems associated with obesity present an ever-growing challenge to physicians involved in their fertility care. The spectrum of reproductive problems associated with obesity encompasses a wide range of disorders including infertility problems, miscarriage and pregnancy complications. In this review, we aim to discuss the impact of obesity on the various aspects of female reproductive function with focus on the clinical aspects of fertility problems in obese women. We finally comment on the available therapeutic options available to this group of women.     

中南地区正常人血清α_1─抗胰蛋白酶检测结果分析

通过对中南地区１５７７例正常人的血清α_１－抗胰蛋白酶（α_１－ＡＴ）水平的测定，结果２０～４０岁组正常值为１３６．９ｍｇ％，４１～６０岁组正常值为１２９．３ｍｇ％，男女性别间的α_１－ＡＴ水平差异无显著意义。而两个年龄组间差异有显著意义。并对测定结果作了分型。     

133Granulation Tissue Induction by Lassar Ointment vs. Collagen‐Polyvynilpyrrolidone in Venous Ulcers

Venous leg ulcers derived from tissue destruction is the consequence of a chronic inflammatory process that produces pain and physical disability, diminishing quality of life in patients. In this work, Lassar ointment and lyophilized collagen‐polyvinylpyrrolidone were administered separated each on one half in the same ulcer to 9 patients at the beginning and every 4 days. On day 16, all patients were auto‐grafted with partial thickness skin. Granulation tissue and graft integration were assessed clinically during 3 months. Inflammatory infiltrate, type I and III collagens, elastic fibers, alkaline phosphatase as well as blood vessels were evaluated histologically or histochemically in biopsies taken at the beginning and 16 days after the local treatment. Clinically and morphologically, both treatments demonstrated appropriate granulation tissue promotion and optimal graft integration since the beginning. Nevertheless, in Lassar ointment treated group regionalization of alkaline phosphatase activity was observed, as well as the presence of granuloma in 2 of the 9 patients. In conclusion, Lassar ointment or lyophilized collagen‐polyvinylpyrrolidone are two different promoters of granulation tissue in venous leg ulcers, however Lassar ointment has the capability to produce granuloma and an exacerbated immune response; in consequence, ulcer recidivism could be present, may be due to mineral deposits in the wound.     

颅脑外伤后肢体痉挛状态的显微外科治疗

目的 探讨显微外科治疗颅脑外伤后肢体痉挛状态的疗效.方法 回顾分析2006年7月至2008年7月实施的21例显微外科治疗颅脑外伤后肢体痉挛状态,根据不同病例采用相应的选择性周围神经部分切断术,包括:胫神经、肌皮神经、正中神经、尺神经和腰骶段脊神经后根,共计50个肢体.结果 术后随访2～24个月,全部患者术后立即感相应肢体痉挛状态缓解,随访期间缓解率为98%(49/50).随访期间运动功能改善率为86%(18/21),生活质量提高率为95%(20/21).术后发生肢体麻木、疼痛等感觉异常26个(52%),肌力下降18个(36%),随访期间均见好转.术后痉挛状态复发1个(2%).结论 选择性周围神经部分切断术是治疗颅脑外伤后肢体痉挛状态安全有效的方法.选择适应证及手术时机和术后坚持康复训练是保证疗效的关键.     

微血管减压术治疗舌咽神经痛16例临床分析

目的　研究舌咽神经痛 (glossopharyngealneuralgia,GPN)手术治疗的最佳术式 ,评估微血管减压手术(microvasculardecompression ,MVD)的效果、并发症和随访结果 ,探讨可能的治疗机制。方法　 2 0 0 0年 12月到2 0 0 3年 10月间 ,16例GPN患者接受了MVD ,无一例行神经根切断术。患者全部进行了电话或信件随访。结果　15例患者术后疼痛消失 ,1例患者为不典型GPN ,术后疼痛减轻。 1例患者术后出现轻度声音嘶哑和吞咽困难 ,1例患者出现偶发干咳。本组患者平均随访时间为 14 .1± 6 .3月 ,随访期间无一例复发。结论　MVD是治疗舌咽神经痛的一种安全、有效的手术方式 ,尤其适用于典型的GPN患者。     

Protein ubiquitination in postsynaptic densities after transient cerebral ischemia.

The mechanisms underlying neurologic deficits and delayed neuronal death after ischemia are not fully understood. In the present study, we report that transient cerebral ischemia induces accumulation of ubiquitinated proteins (ubi-proteins) in postsynaptic densities (PSDs). By immunoelectron microscopy, we demonstrated that ubi-proteins were highly accumulated in PSD structures after ischemia. On Western blots, ubi-proteins were markedly increased in purified PSDs at 30 minutes of reperfusion, and the increase persisted until cell death in the CA1 region after ischemia. In the resistant DG area, however, the changes were transient and significantly less pronounced. Deposition of ubi-proteins in PSDs after ischemia correlates well with PSD structural damage in the CA1 region as viewed by electron microscopy. These results suggest that the ubiquitin-proteasome system fails to repair and remove damaged proteins in PSDs. The changes may demolish synaptic neurotransmission, contribute to neurologic deficits, and eventually lead to delayed neuronal death after transient cerebral ischemia.     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

Prospective randomised comparison of current coagulation and injection sclerotherapy for the outpatient treatment of haemorrhoids

The feasibility and early results of a new technique of outpatient proctoscopic coagulation of haemorrhoids by means of an electronic probe (Ultroid^®, Microvasive Inc., USA) were evaluated in comparison to conventional injection sclerotherapy. Age, symptom and sex-matched groups were analysed before and 6 weeks after outpatient treatment, using scoring systems (n=51). A mean of 6.2±0.4 ml of phenol in oil were injected over 2.4±0.2 min compared to a mean current of 15.8 ±0.2 mA over a period of 11.9±0.8 min (p<0.001, treatment time). Sclerotherapy was found significantly less tedious than coagulation. More patients complained of discomfort during coagulation, but the difference in tolerance scores between the 2 groups was not significant. Three patients in the coagulation group but none in the injection group refused to be treated by the same method again due to discomfort. Significant benefits were achieved by both modes of treatment after 6 weeks. The early cure rates for bleeding were 84% for sclerotherapy and 64% for coagulation (p=0.2) and for prolapse 56% and 44% respectively (p=0.72). Injection sclerotherapy is preferable to Ultroid^® coagulation for the outpatient treatment of haemorrhoids because it is a quicker, less tedious and more comfortable procedure with equally effective early results.

---

Résumé La réalisation et les premiers résultats d'une nouvelle technique de coagulation ambulatoire des hémorroïdes au moyen d'une sonde électronique (Ultroïd, Microvasive inc. USA) on été évalués par comparaison avec la sclérothérapie conventionnelle. Deux groupes appariés selon l'âge, les signes et le sexe ont été analysés avant et six semaines après un traitement ambulatoire en utilisant un score (n=51). Une moyenne de 6,2±0,4 ml d'huile phéniquée a été injectée en 2,4±0,2 mn comparée à une application de courant moyen de 15,8±0,2 mA dans une période de 11,9±0,8 mn (p<0,001, temps de traitement). La sclérothérapie a été trouvée moins pénible que la coagulation. Plus de malades se plaignaient d'inconfort durant la coagulation mais la différence de tolérance n'était pas significative entre les deux groupes. Trois malades dans le groupe de coagulation ont refusé de poursuivre le traitement en raison du disconfort contre aucun malade dans le groupe d'injection. Les résultats furent bons dans les deux groupes après six semaines. Les résultats immédiats pour les saignements étaient de 84% et de 64% pour la coagulation (p=0,2) et pour les procidences de 56% pour la scléro-thérapie contre 44% pour la coagulation (p=0,72). Les injections sclérosantes sont préférables à la coagulation Ultroid comme traitement ambulatoire des hémorroïdes car il s'agit d'un procédé plus rapide, moins pénible et plus confortable avec des résultats immédiats aussi bons.

---

---

Paper presented at the Spring Meeting of the British Society of Gastroenterology, University of Warwick, UK, March 1990     

Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.