Tacrolimus Exposure and Evolution of Renal Allograft Histology in the First Year After Transplantation

Tacrolimus has a narrow therapeutic window and is characterized by a large inter-individual variability in bioavailability. The impact of tacrolimus exposure on subclinical evolution of graft histology has not been studied in renal recipients. This analysis included 239 protocol biopsies (obtained at implantation, 3 and 12 months) of 120 consecutive kidney recipients treated with tacrolimus, mycophenolate mofetil (MMF) and corticosteroids. Biopsies were scored according to the Banff 2001 criteria and a chronicity score was calculated. Prospective pharmacokinetic data were included in the analysis (5544 tacrolimus predose blood concentrations and tacrolimus AUC(0-12) at 3 and 12 months). Higher donor age and higher number of human leukocyte antigen-DR (HLA-DR) mismatches were independent predictors of subclinical acute rejection at 3 months, present in 8.7% of patients. The number of HLA-DR mismatches was independently associated with biopsy-proven clinical acute rejection. Biopsy-proven acute rejection episodes and low mean tacrolimus exposure were independently associated with higher increase in chronicity scores between 3 and 12 months after transplantation. This observational study suggests that rejection phenomena and immune-mediated mechanisms remain important in the early progression of chronic allograft pathology. Tacrolimus doses or systemic exposure were not associated with lesions of calcineurin inhibitor nephrotoxicity, suggesting that other factors determine susceptibility to tacrolimus nephrotoxicity.     

喉咽癌手术放疗后甲状腺功能减退

本文对４２例喉咽癌手术及放疗后患者甲状腺功能的变化的初步探讨表明：在治疗结束后不同时间内有５７．１％的患者Ｔ４降低及（或）ＴＳＨ升高，其中放疗结合甲状腺部分切除者其发生率高达７３．９％，而未行甲状腺部分切除者仅３８．５％，两者呈显著差异（Ｐ＝０．０３）。术前或术后放疗对甲状腺功能影响较小，亦无明显差异。发生时间在治疗结束后２年内尤其在１年左右为多见。     

Increased incidence of congenital hypothyroidism due to iodine deficiency

BACKGROUND: The incidence of congenital hypothyroidism (CH) is expected to be elevated in iodine-deficient areas. In this study, the authors aimed to determine the incidence of transient and permanent CH in a large city which is known to be in the zone of moderate iodine deficiency. METHODS: Newborn babies in Bursa, Turkey, were screened by measurement of serum thyroid-stimulating hormone (TSH) obtained by heel prick. The babies who had a serum TSH >20 mIU/L were recalled for measurement of T4 and TSH in venous serum. RESULTS: A total of 11 770 newborns were screened over a period of 9 years. The incidence of CH was found to be 1/840. However, after excluding the transient cases, permanent CH was diagnosed in 1/2354. It was impossible to distinguish transient patients from permanent CH by initial laboratory tests (P > 0.05). The estimated power of the study in determining the incidence of CH in the population was 90% (P < 0.05). CONCLUSION: The authors conclude that the incidence of CH is very high in their population which warrants a country-wide neonatal screening program. Since transient cases cannot be distinguished and untreated transient hypothyroidism may also cause mental retardation, treatment must be started as early as possible with frequent monitoring to optimize the outcome and identify the transient patients.     

Appropriate Replacement Dose of Thyroxine in Primary Hypothyroidism

ABSTRACT An ultrasensitive thyrotropin (TSH) assay was used to determine how many of 65 patients with primary hypothyroidism on thyroxine (T₄) replacement therapy had suppressed serum TSH. In 13 patients (20%) TSH levels ≤0.1 mlU/l were found, indicating an overdose of thyroxine. After correction of the dose, 48 patients had normal TSH values. Their mean dose of thyroxine was 119 μg/24 hours, and the appropriate replacement dose tended to decline with advancing age. The serum level of thyroid hormones during replacement therapy with thyroxine very imperfectly reflected serum TSH values. It is concluded that overdose of thyroxine is common when suppressed serum TSH is used as an end point. Biochemical follow-up of replacement therapy with thyroxine in primary hypothyroidism therefore requires the use of an ultrasensitive TSH assay in order to detect such suppression. Serum levels of thyroxine or triiodothyronine (T₃) during thyroxine therapy are poor indicators of pituitary TSH secretion and are therefore not useful as parameters of adequate thyroxine dosage.     

尿羟脯氨酸测定及临床意义

本文测定100名健康人尿羟脯氨酸参考值范围、其中藏族12名,经统计学处理男女性别之间、民族之间无显著性差异。测定15名甲状腺机能亢进、6例甲状腺机能减退、50例糖尿病患者尿羟脯氨酸值。结果甲亢在这四组(正常成人甲减、糖尿病)中含量最高,与其它三组比较有显著性差异(P<0.01)。甲减最低与其它三组比较有显著性差异(P<0.02)。糖尿病人略高于正常人。与文献报导基本相符。     

亚临床甲状腺功能减退症患者TSH与肾上腺皮质功能的关系

目的分析亚临床甲状腺功能减退症患者促甲状腺激素(TSH)与肾上腺皮质功能的关系。 方法选取150例亚临床甲状腺功能减退症患者为研究组,甲状腺功能正常的健康人群150例为对照组。比较两组TSH、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、皮质醇(CORT)和促肾上腺皮质激素(ACTH)水平。采用Pearson法分析亚临床甲状腺功能减退症患者TSH水平与ACTH、CORT水平的相关性。 结果与对照组比较,研究组患者TSH、ACTH水平升高,CORT水平降低(P＜0.05)。Pearson分析结果显示,亚临床甲状腺功能减退症患者TSH水平与ACTH水平呈正相关(P＜0.05),与CORT水平呈负相关(P＜0.05)。 结论亚临床甲状腺功能减退症患者血清TSH水平与肾上腺皮质功能指标ACTH、CORT水平存在相关性。     

老年SH患者甲状腺激素水平与冠心病相关性探讨

目的:探讨老年亚临床甲状腺功能减退症血清甲状腺激素与冠心病病变程度的相关性.方法:70例冠心病患者根据冠脉造影结果分为造影正常组30例,单支病变组15例,多支病变组35例,采用放射免疫分析检测TT3,TT4,FT3,FT4,TSH水平.结果:多支病变组的亚临床甲减发生率明显高于造影正常对照组和单支病变组(P＜0.05),亚临床甲减与冠心病多支病变具有相关性(OR=2.20). 结论:亚临床甲状腺功能减退症是冠心病多支病变的危险因素之一.     

NGF prevents further atrophy of cholinergic cells of the nucleus basalis due to cortical infarction in adult post-hypothyroid rats but does not restore cell size compared to euthroid rats

We have tested the hypotheses that nerve growth factor treatment in adult post-hypothyroid rats can: (1) restore cross-sectional area of cholinergic cells of the nucleus basalis and (2) prevent further atrophy of these neurons following cortical infaction. In addition, we assessed the expression of p75^NGFR and p140^trkA mRNAs in the nucleus basalis cells of post-hypothyroid rats. Rats were rendered hypothyroid by the addition of propylthiouracil to their diet beginning on embryonic day 19 until the age of 1 month. At this time both the pups and their dams continued to receive 0.05% propylthiouracil in their diet and the pups were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and thyroxine levels were restored to normal by daily subcutaneous administration of physiological levels of thyroxine. Morphometric analysis identified atrophied nucleus basalis magnocellularis cholinergic cells at two ages, days 75 and 105, identified by in situ hybridization for p75^NGFR and p140^trkA mRNAs in methylene blue stained cells (day 75) and choline acetyltransferase immunostaining (day 105). The mean number of silver grains (pixels) per μm² (mean±S.E.M.) of cell body cross-sectional area for p75^NGFR mRNA in the nucleus basalis magnocellularis of euthyroid rats was 3.43±0.89, which was not statistically different from post-hypothyroid animals (4.02±1.07). A similar finding was noted for p140^trkA mRNA: mean number of grains in the euthyroid group was 5.54±0.96 and was not statistically different from the post-hypothyroid group (6.32±1.45). Nerve growth factor treatment in adulthood (between days 75 and 82) did not restore cross-sectional area from early thyroid deprivation. However, it prevented further atrophy of nucleus basalis magnocellularis neurons following cortical devascularization inflicted in adulthood (day 75).     

P300等诱发电位对亚临床肝性脑病早期诊断的意义

目的:观察事件相关电位P_(300)、体感诱发电位、视觉诱发电位和脑干听觉诱发电位在亚临床肝性脑病诊断中的意义。方法:50例亚临床肝性脑病患者进行了心理测验,并做了头颅CT和视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位检查,30例正常人做为对照组。结果:亚临床肝性脑病的心理测验,韦氏法智力低下率为76％,视觉诱发电位异常率为13％,脑干听觉诱发电位异常率为20％,体感诱发电位异常率为40％,事件相关电位异常率为71％,正常对照组四种诱发电位的正常率是100％。头颅CT结果与亚临床肝性脑病无关。结论:视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位在亚临床肝性脑病中是异常的。事件相关电位更为敏感,对亚临床肝性脑病的早期诊断有重要意义。