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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. 相似文献
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. 相似文献
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CF Poets VA Stebbens JR Alexander WA Arrowsmith SAW Salfield DP Southall 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(6-7):536-541
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. 相似文献
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To improve identification of preneoplastic bladder cancer cells,we have studied two enzyme histochemical changes in bladdertumors induced in male Fisher 344 rats by the carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine.In early areas of focal nodular hyperplasia there was a dramaticincrease in staining for NADH:menadione oxidoreductase (diaphorase)activity. In nonfocal areas as well, there were many individualcells with intense staining, while the controls were of uniformmoderate staining. Large papillomas and carcinomas often showedheterogeneous staining. - Glutamyltranspeptidase (GGT) was absentfrom normal urothelium and from all tumors except the most advancedcarcinomas and large papillomas. In old, carcinogen-exposedanimals, GGT activity was seen in the luminal surface of tumorsand in the interlesion urothelium. In newborn rats and in ratswith regenerative hyperplasia following wounding of the urothelium,the diaphorase staining was less than that in the untreatedadult. Our findings suggest that increased diaphorase activitymay serve to identify early islands of carcinogen-induced, enzymaticallyaltered bladder cells, while GGT will not. 相似文献
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Prevalence and infectivity of hepatitis G virus and its strain variant, the GB agent, in volunteer blood donors in Taiwan 总被引:2,自引:0,他引:2
BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) is high in non-virus-inactivated plasma products, but, persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS: Stored samples from transfusion donors and recipients in a prospective study of posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein (anti-E2). RESULTS: Thirty-two (2.1%) of the 1500 qualified donors were positive for HGV RNA. Twenty-four persons had received a transfusion of blood from one of these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA before transfusion. Of the remaining 21 recipients, 8 became viremic after transfusion, while the other 13 were not infected. Four of the eight infected recipients were persistently positive for HGV RNA, while four became negative in 1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti-E2 positivity. Comparison of the viral titer, viral sequences at E2, storage period of blood donations, and clinical data in the infected and noninfected recipients revealed no significant differences. However, the noninfected recipients seemed to have a higher prevalence of anti-E2 before transfusion. CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is 2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in the recipients. In half of infected recipients, clearance of HGV occurs. Anti-E2 appears in most recipients whose viremia is cleared. 相似文献
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