Endothelial markers and homocysteine in patients with classic Fabry disease

Aim : Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of α-galactosidase A, a lysosomal enzyme. It is a multisystem disorder characterized by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement. The recent availability of genetically engineered enzyme offers an effective targeted treatment approach, but also emphasizes the need for surrogate markers to delineate organ damage and monitor the efficacy of enzyme replacement therapy (ERT). Methods : Multiple endothelial factors and plasma homocysteine concentrations were investigated in 12 consecutive hemizygous males with classic Fabry disease and 15 controls as part of an exhaustive baseline evaluation prior to ERT. Results : Compared with the controls, plasma concentrations of homocysteine were significantly ( p > 0.01) higher in patients with Fabry disease in the absence of chronic renal failure or vitamin deficiency. Plasma concentrations of vascular cell adhesion molecule-1 were also significantly ( p > 0.05) higher in the patients, and there was a trend for decreased endothelin-1 levels. No difference was found in serum intercellular adhesion molecule-1, plasma P-selectin, serum E-selectin and plasma thrombomodulin between the patients and controls.
Conclusions : The results do not reveal measurable evidence for endothelial and leukocyte activation that could reliably serve as surrogate markers for routine monitoring of the efficacy of ERT in patients with Fabry disease. While the exact origin and clinical significance of hyperhomocysteinaemia in Fabry disease remains to be studied in a larger cohort of patients carefully monitored for their concurrent medications, especially carbamazepine, we suggest that patients may benefit from folic acid or multivitamin therapy to treat this additional vascular risk factor, when present.     

Hypoxaemia in infants with respiratory tract infections

Nineteen infants who were graduates from special care baby units underwent two overnight tape recordings of oxygen saturation (SaO2) and breathing movements; one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the other when free of infection. Baseline SaO2 was lower during infection (median 99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%) below the normal lower limit for full-term infants (97%). The median number of apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h, p less than 0.02). The median number of episodic desaturations (SaO2 less than or equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05), with the exception of one patient who had extremely increased values during infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant, however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia may thus occur during respiratory tract infection in a proportion of infants graduating from special care baby units. Such hypoxaemia may have potentially deleterious effects.     

骨形态发生蛋白基因治疗骨缺损

目的:总结骨形态发生蛋白在骨组织工程基因治疗骨缺损中的进展。资料来源:应用计算机检索PubMed数据库1990-01/2007-01相关骨形态发生蛋白基因治疗骨缺损方面的文献,检索词"BMP,tissue engineering,gene therapy,bone defect",限定文献语言种类为English。资料选择:选取包括骨形态发生蛋白基因治疗骨缺损的文献,阅读全部文章的文题和大部分文章的摘要。纳入标准:文章所述涉及骨形态发生蛋白及其基因治疗骨缺损。排除标准:重复性研究和Meta分析类文章。资料提炼:共检索到99篇关于骨形态发生蛋白及基因治疗骨缺损的文献,最终纳入30篇符合标准的文献。资料综合:骨组织工程是组织工程学的重要组成部分,它是指利用组织工程学进行骨组织缺损的修复或重建,包括种子细胞、特定的细胞因子和载体。骨形态发生蛋白是一种疏水性酸性蛋白质,在临床实践中,已证实其能促进骨愈合,被认为是目前最强有力的一种骨诱导因子。基因治疗在许多方面都代表了一种增进骨再生方法的理念。其允许特异的基因产物转移至精确的解剖学部位。运用骨形态发生蛋白基因于骨组织工程领域以治疗骨缺损是目前新的热点。骨组织中的骨形态发生蛋白以及骨形态发生蛋白的表达和功能由于他们显著的生物学作用而被长时间的研究。结论:应用骨形态发生蛋白基因疗法可以成功诱导骨和软骨的发生,为骨缺损的治疗开辟了新的解决途径。     

CLINICAL AUDIT: IS DAY-CASE ADENOTONSILLECTOMY SAFE?

SUMMARY The trend towards day-case procedures is growing, as a consequence not only of improved medical care but the increasing importance of economic considerations in today's healthcare environment. In the largest worldwide study to date to assess the safety of day-case adenotonsillectomy, we reviewed the records of 4386 patients at the otolaryngology department of the Bradford Royal Infirmary. We found a reactionary haemorrhage rate of 0.57%. All patients who underwent surgery in the morning session had presented with haemorrhage and returned to the operating theatre before the end of the afternoon session. We discuss the implications of these findings, and consider that with careful monitoring day-case tonsillectomy and/or adenoidectomy may safely be introduced.