Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants

Background: Only few data exist on pharmacokinetics of tacrolimus in children. Patients: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years) received tacrolimus after renal transplantation; 10 of these after biopsy-proven steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on CsA, and one child was treated primarily after transplantation because of severe liver involvement in nephronophthisis. Pharmacokinetic investigations were performed after establishing a stable maintenance dose with trough levels in the desired window of 5-12 ng/ml. Results: Mean follow-up time was 6 months (range 3-25 months). Eleven patients were still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them also developed diabetes mellitus),and one patient was subsequently switched to conventional immunosuppression because of tacrolimus-associated nephrotoxicity. All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity. At the time of switch, median serum creatinine was 234±82 7mgr;mol;l and 6 months after switch 201±99 &mgr;mol/l. All grafts are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 0.036-0.30 mg/kg). Mean trough level was 7.1±2.6 ng/ml in the morning and 6.5±2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120 min after application, and the mean maximum concentration (Cmax) was 15.2±6.7 ng/ml. Mean area under the curve (AUC) was 104±33 ng * h/ml, with a range from 65 to 169 ng * h/ml. No patient had unsatisfactorily low trough levels during the study. There was only a weak but significant (P<0.05) correlation between dose per kg body weight and AUC and, as expected, an excellent correlation (r²=0.73, P<0.001) between AUC and trough level. Conclusion: Because of interindividual variation between patients, therapeutic drug monitoring of tacrolimus is mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most patients. We recommend the performance of at least one pharmacokinetic study after establishing stable FK 506 trough levels to ascertain a safe profile.     

组织多肽特异性抗原在乳腺癌中的临床研究

OBJECTIVE: To investigate the expression of serum tissue polypeptide-specific antigen (TPS) in breast cancer patients and its clinical value in such cases. METHODS: Altogether 160 subjects (90 patients with breast cancer, 40 with benign breast lesions, and 30 healthy subjects) were enrolled in this study. The serum TPS and CA153 levels were measured by ELISA in all the subjects. RESULTS: The levels and positivity rate of serum TPS and CA153 in breast cancer group were significantly higher than those in the normal subjects group and benign lesion group (P<0.01), and became even higher as the malignancy progressed. High serum TPS level was detected in the cancer patients in stage I. Serum TPS level was the most sensitive to bone metastasis of the malignancy, but its highest levels occurred in cases of lymphoid node metastasis (P<0.05). In patients who responded favorably to the treatment, serum TPS and CA153 levels were significantly reduced (P<0.05), but the reduction in TPS levels tended to be more obvious (P<0.05). CONCLUSION: Serum TPS can be used as a very useful and sensitive tumor marker in the diagnosis of breast cancer, especially in case of bone metastasis, and may be of great value in clinical decision-making and assessment of therapeutic effect.     

爱母分娩工程初探——产程系列服务模式

爱母分娩工程的核心是产时分娩的管理，除医疗技术水平为重要因素外，改善产科系列服务模式，加强孕妇夫妇有关培训与健康教育，加强保健与临床的结合，对爱母分娩工程的作用亦是举足轻重的。广东省妇幼保健院试运行产时分娩管理新模式、产科系列服务新模式，提高了产科质量和社会效益及经济效益。     

左旋多巴对弱视眼视诱发电位影响的研究

目的:探讨左旋多巴治疗弱视的效果。方法:正常眼和弱视眼服用单次剂量左旋多巴前后进行图形视诱发电位(pattem visual evoked poten-tial,PVEP)检测。结果:正常眼服药后中空间频率PVEP的N_1P_1振幅和高空间频率PVEP的P_1N_2振幅增大,弱视眼服药后低空间频率PVEP的N_1波潜伏期和中空间频率PVEP的P_1波潜伏期缩短。结论:左旋多巴可改善弱视眼的视功能,可作为弱视的一种新的治疗方法。眼科学报1997;13:182—185。     

Evaluation and audit in a paediatric disability service

Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally.     

Monoclonal antibodies against carcinoembryonic antigen (CEA) used in a solid-phase enzyme immunoassay. First clinical results

A solid-phase enzyme immunoassay using both mouse monoclonal and goat polyclonal antibodies against carcinoembryonic antigen (CEA) was developed. The assay detects 0.6 to 1.2 ng of CEA per ml of serum and has 3 incubation steps which can be performed in 1 day. Polystyrene balls coated with polyclonal goat anti-CEA antibodies are first incubated with heat-extracted serum samples. Bound CEA is then detected by addition of mouse monoclonal antibodies, followed by goat IgG anti-mouse IgG1 coupled to alkaline phosphatase. Results with this enzyme immunoassay using monoclonal antibodiies (M-EIA) have been compared with those obtained by the conventional inhibition radioimmunoassay (RIA) using goat antiserum. Three hundred and eighty serum samples from 167 patients with malignant or non-malignant diseases and from 134 normal individuals with or without heavy smoking habits were analyzed by the 2 assays. Excellent correlation between the results of the 2 assays was obtained, but the M-EIA, using monoclonal antibodies from a single hybridoma, did not discriminate better than the conventional RIA between CEA produced by different types of carcinoma and between CEA associated with malignant or non-malignant diseases. Follow-up studies of several patients by sequential CEA determinations with the 2 assays showed that the M-EIA was as accurate as the RIA for the detection of tumor recurrences.     

新生儿G6PD缺陷病和晚发性维生素K缺乏症的特点与预防

目的 探讨新生儿C6PD缺陷病和晚发性维生素K缺乏症的危害与预防措施。方法 回顾分析1995-2000年儿内科住院的1周-2月(不含2月)的婴儿3104例次，其中病死56例。结果 1周-2月的小婴儿占住院患儿的19．34％，其中新生儿G6PD缺陷病239例，占7．70％；晚发性维生素K缺乏症92例，占2．96％。死因的第2、3位分别是晚发性维生素K缺乏症(13例，占23．21％)和新生儿C6PD缺陷病(12例，占21．43％)，两者的病死率分别为14．13％和5．02％，极显著高于(x^2＝17．59，P＜0．01)或相近于(x^2＝0．88，P＞0．05)肺炎的3．57％。新生儿G6PD缺陷病合并感染占38．49％、低氧血症占23．35％、低血糖占19．25％、酸中毒占15．90％，继发胆红素脑病占13．81％。晚发性维生素K缺乏症出现抽搐占90．22％、胃肠、注射部位出血占60．89％；CT证实颅内出血占98．91％。结论 1周-2月的小婴儿约占住院患儿的两成，新生儿G6PD缺陷病和晚发性维生素K缺乏症的病死率均很高，两者是除肺炎外最主要的死因。提议制定并推广预防这2种疾病的常规措施，并参照国内外相应的现状拟出其具体内容。     

Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of expression and correlation with clinical outcome

Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and Epstein-Barr virus infection has been reported to be a cause of this disease. Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF-1), exhibited high expression in organs in which breast cancer metastases are often found. The metastatic pattern of NPC is quite similar to that of malignant breast tumors. In this study, we investigated the expression of CXCR4 in nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different staining patterns, which included localization in the nucleus, membrane, cytoplasm or a combination of them. The staining intensity was also variable among samples. The metastatic rates in patients with high compared to low or absent expression was 38.6% versus 19.8%, respectively (P = 0.004). High expression of CXCR4 was associated with poor overall survival (OS = 67.05% versus 82.08%, P = 0.0225). These results suggest that CXCR4 may be involved in the progression of NPC and that a high level of CXCR4 expression could be used as a prognostic factor.     

Differential expression of lactoseries carbohydrate epitopes HNK-1, CD15, and NALA by olfactory receptor neurons in the developing chick

 The formation of the nasal lining with its sensory and its nonsensitive respiratory epithelium requires a spatially ordered pattern of cellular differentiation. Aiming at identifying cell recognition molecules that may be involved in cellular differentiation steps, we applied a panel of antibodies to terminal carbohydrate sequences of the lactoseries on the developing chick olfactory epithelium. This approach is based on the idea that these terminal sugar residues may be involved in certain steps of maturation. Restricted expression of three epitopes NALA, HNK-1, and CD15 was observed in olfactory receptor neurons. The first immature olfactory receptor neurons were observed by day 3 of incubation, expressing the HNK-1 epitope, whereas a total epithelial staining was observed for NALA. By day 9 of incubation high numbers of HNK-1 positive immature olfactory receptor neurons were observed. At the same time mature olfactory receptor neurons showed immunoreactivity for CD15, whereas NALA was still expressed throughout the whole epithelial cell population. However, there was a pronounced staining in the population of mature olfactory receptor neurons. Around hatching only CD15 was detectable in (mature) olfactory receptor neurons, whereas HNK-1 and NALA immunoreactivity have switched to glandular and sustentacular cells respectively. The differentiation-dependent expression patterns of these three cell surface molecules suggest them as suitable markers to explore mechanisms that determine embryonic olfactory receptor neurogenesis. Accepted: 15 October 1997