Proliferative ischaemic retinopathy in a case of systemic lupus erythematosus and antiphospholipidic syndrome

PURPOSE/METHODS: We report a 34-year-old woman with sytemic lupus erythematosus (S.L.E.) and antiphospholipidic syndrome which presented severe ischaemic retinopathy and neovascular proliferation. RESULTS/CONCLUSIONS: We achieved no progression of the disease and stabilization of visual acuity with panphotocoagulation. We recommend periodic ophtalmologic exams because of the scarce symptomatology.     

Pulmonary histiocytosis X. Report of a case and review of the literature

Histiocytosis X or Langerhans cell histiocytosis is an infrequent disease, which consists on proliferation of Langerhans cells. The etiology is unknown. Diagnosis is reached by electron microscope study of the biopsy, in which the Birbeck intracytoplasmatic granules of the Langerhans cells are found and/or by immunohistochemistry procedures able to detect S-100 antigen and CD1 cells. Diagnosis can also be reached with a bronchoalveolar lavage in which CD1 cells will appear in a score higher than 5%. We present the case of a 16 year-old girl that first appeared with a pulmonary lesion with a honey comb X-ray pattern and unsyntomatic mandibular bone affectation. Diagnosis was reached by biopsy study using S-100 antigen detection procedures. We consider this case an important one due to the infrequency of this particular disease.     

Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum

Region-specific up-regulation of the cyclic AMP pathway is considered an important molecular mechanism in the origin of the somatic manifestations of the withdrawal syndrome to known drugs of abuse. Nevertheless, the existence of a withdrawal syndrome after prolonged cannabinoid administration has long been a controversial issue. Recent studies, in different species, have shown that withdrawal to prolonged cannabinoid exposure precipitated by the cannabinoid antagonist SR141716A is characterized by physical signs underlying impairment of motor coordination. Interestingly, cannabinoid withdrawal is accompanied by an increase of adenylyl cyclase activity in the cerebellum. Here, we investigate the functional role of the cyclic AMP pathway in the cerebellum in the establishment of cannabinoid withdrawal. We show that after SR141716A precipitation of cannabinoid withdrawal, basal and calcium-calmodulin-stimulated adenylyl cyclase activities as well as active PKA in the cerebellum increase in a transient manner with a temporal profile which matches that of the somatic expression of abstinence. Selectively blocking the up-regulation of the cyclic AMP pathway in the cerebellum, by microinfusing the cyclic AMP blocker Rp-8Br-cAMPS in this region, markedly reduced both PKA activation and the somatic expression of cannabinoid withdrawal. Our results (i) directly link the behavioural manifestations of cannabinoid withdrawal with the up-regulation of the cyclic AMP pathway in the cerebellum, pointing towards common molecular adaptive mechanisms for dependence and withdrawal to most drugs of abuse; (ii) suggest a particular role for the cerebellum as a major neurobiological substrate for cannabinoid withdrawal.     

Recurrent hydrochlorothiazide-induced pulmonary edema

Hydrochlorothiazide-induced pulmonary edema is an unusual but life-threatening adverse reaction. It causes hypoxemia, hypotension, tachycardia, fever, and occasionally electrocardiographic and echocardiographic abnormalities. The mechanism of production is, probably, idiosyncratic. Received: 26 May 1997 Accepted: 13 January 1998     

Tetrahydrobiopterin responsiveness in patients with phenylketonuria

OBJECTIVES: To investigate the BH4 response in a group of patients with phenylketonuria (PKU) in order to offer this alternative treatment to the responsive patients. DESIGN AND METHODS: The 24-h-long Phe/BH4 loading test was performed on 64 PKU patients requiring dietary treatment. RESULTS: All patients with mild-PKU and 75% of patients with moderate-PKU were BH4 responsive, while only 11% of classic-PKU patients showed good/partial response (P < 0.0001). The percentages of Phe decrease after the BH4 loading test were significantly different in the three PKU phenotypes (mild PKU: 67.9 +/- 18.7; moderate PKU: 37.4 +/- 16.8; and classical PKU: 21.9 +/- 13.7; ANOVA with Bonferroni correction: P < 0.0001). We report four mutations (P147S, D222G, P275S, and P362T) not previously associated with BH4 responsiveness, all of them combined with mutations with zero predicted residual activity. CONCLUSION: Both the percentage of Phe decrease and the Phe value achieved 24 h after BH4 loading are valuable data in predicting a response. We report four mutations not previously associated with BH4 responsiveness.     

SEVENTY-TWO HOUR COMPARISON OF METHYLPREDNISOLONE SULEPTANATE AND METHYLPREDNISOLONE SODIUM SUCCINATE IN PATIENTS WITH ACUTE ASTHMA

SUMMARY The efficacy and safety of the methylprednisolone prodrugs methylprednisolone suleptanate and methylprednisolone sodium succinate were evaluated in a multicentre, randomised, double-blind, double-dummy parallel study of 88 patients hospitalised with acute asthma. Each study drug was administered as a bolus intravenous injection of 40mg methylprednisolone equivalents every 6 hours for 48 hours. Methylprednisolone 32mg was administered orally 6 hours after the last dose. Pulmonary function, medical events, and clinical laboratory values were assessed at predefined intervals before and during the 72-hour study. The primary response measure of pulmonary function was per cent predicted forced expiratory volume in one second (FEV₁) at 48 hours. Secondary response measures were peak expiratory flow rate (PEFR) and FEV₁/forced vital capacity (FVC) ratio. Although both drugs demonstrated within-group mean changes from baseline (starting at 6 hours) that were statistically significant for each response, there were no statistically significant differences between the two groups. The mean percent predicted FEV₁ at 48 hours and mean per cent change from baseline were 64% and 13% (p<0.0001) for the methylprednisolone suleptanate group and 67% and 17% (p<0.0001) for the methylprednisolone sodium succinate group, respectively. The mean PEFR and FEV₁/FVC ratio at 48 hours were 5.77 l/s and 73% for the methylprednisolone suleptanate group and 5.78 l/s and 76% for the methylprednisolone sodium succinate group, respectively. There were no clinically or statistically significant between-group differences in any of the safety parameters. In this study, methylprednisolone suleptanate and methylprednisolone sodium succinate have been shown to be therapeutically equivalent in the treatment of patients hospitalized with acute asthma.     

携带LacZ的腺病毒载体在牵引骨痂局部转染成纤维细胞和成骨细胞的表达

目的:利用小鼠胫骨牵引成骨动物模型,在牵引成骨过程中局部给予携带了LacZ的腺病毒载体后观察其表达情况,以探讨基因治疗促进骨折愈合的可行性。方法:实验于2004-10/2006-01在中南大学湘雅三医院完成。①实验分组:取雄性8周龄CD-1小鼠20只,随机数字表法分为实验组和对照组,每组各10只。②实验方法:所有小鼠接受左胫骨中上段骨干横行截骨安置特制延长外固定架,胫骨牵引过程包括5d静止期,10d牵引期,牵引速率为0.1mm/次,2次/d,共0.2mm/d。牵引期第7天实验组牵引骨痂局部注射5μL携带了LacZ的腺病毒载体,对照组局部注入等量未含LacZ腺病毒液。③实验评估:注射后第3天麻醉后杀取动物,采集左胫骨标本,分别作组织学检查和组织化学分析。结果:纳入小鼠20只,均进入结果分析。在牵引第10天,牵引骨痂中纤维间区形成,两端的新生骨由骨折两端中心生长延伸。骨髓腔内外可见大量新生骨形成。X-Gal底物染色显示,在实验组新生骨组织内可见大量细胞呈阳性染色;而对照组未发现阳性染色细胞。结论:在牵引成骨过程中,骨痂局部注射携带LacZ的腺病毒,能成功转染局部的成纤维细胞及成骨细胞,并表达LacZ基因,为临床应用基因治疗促进骨牵引延长或骨折愈合提供可行性。     

Establishing a phase I unit: organisation

Summary— The organisation of a phase I unit must take into account the safety, quality and scientific requirements of such studies. The clinical pharmacology unit demands a highly qualified staff, as well as intensive care equipment. The investigator, generally a clinical pharmacologist who coordinates the different tasks as a project leader, has often to initiate a fruitful collaboration with a specialised consultant staff in order to implement the studies.