Randomized, Open-Label, Phase IV, Korean Study of Kidney Transplant Patients Converting From Cyclosporine to Prolonged-Release Tacrolimus Plus Standard- or Reduced-Dose Corticosteroids.

BACKGROUND: This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS: At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS: Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION: Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

Impact of vitamin D on proteinuria, insulin resistance, and cardiovascular parameters in kidney transplant recipients.

Low vitamin D levels prevalent in patients with chronic kidney disease have been reported to be associated with proteinuria, insulin resistance, and cardiovascular disease. Kidney transplant recipients are also susceptible to low vitamin D levels but their clinical significance is uncertain. This study investigated the prevalence and association of vitamin D insufficiency with proteinuria, insulin resistance, and cardiovascular parameters among 95 living donor kidney transplant recipients. Levels of 25-hydroxyvitamin D [25(OH)D] were stratified into an insufficient group [25(OH)D≤30 ng/mL; n=19] versus a normal group [25(OH)D>30 ng/mL; n=76]. Proteinuria (urinary protein-creatinine [P/C]≥0.2 mg/mg), insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) and cardiovascular parameters were compared between groups. Twenty percent of subjects showed vitamin D insufficiency. Proteinuria was higher among the vitamin D insufficient than the normal group (47.4% vs 18.7%; P=.02). 25(OH)D levels inversely correlated with urinary P/C ratio and intact parathyroid hormone (I-PTH) levels (r=-.24, P=.02 and r=-.23, P=.02, respectively). No correlations were observed between 25(OH)D levels and HOMA-IR scores or cardiovascular parameters. On univariate analysis, proteinuria and i-PTH levels were independent predictors of vitamin D insufficiency (P<.01 and P=.03, respectively). Multivariate analysis demonstrated proteinuria to be a significant predictor of vitamin D insufficiency (odds ratio=4.526; P=.03). In conclusion, vitamin D insufficiency was common and significantly associated with proteinuria among kidney transplant recipients. Additional studies are needed to clarify the causal relationship of vitamin D insufficiency with proteinuria and to determine the role of vitamin D supplementation to attenuate the development of proteinuria.

Ultrasensitive electrical detection of nucleic acids by hematin catalysed silver nanoparticle formation in sub-microgapped biosensors.

An ultrasensitive electrical detection method of nucleic acids has been demonstrated on sub-microgapped biosensor. In this method, peptide nucleic acid (PNA) probes were firstly immobilized in the gap areas of a pair of interdigited microelectrodes and then were hybridized with their complementary target DNA. After hybridization, hematin molecules were introduced into the DNA strand via zirconium-phosphate and zirconium-carbonate chemistries. The newly attached hematin molecules act as a catalyst to accelerate reducing ammoniacal silver ion to form silver nanoparticles, which span the gap of the interdigitated microelectrode. The conductance of the silver nanoparticles directly correlated with the number of the hybridized DNA molecules. Nearly 1fM sensitivity was achieved under optimal conditions. This approach is also applicable to the detection of RNA.

Genomic organization of the canine p53 gene and its mutational status in canine mammary neoplasia.

To determine whether canine malignancies share common genetic lesions with their human counterparts, and are thus potentially interesting model systems in which to pose questions regarding tumor etiology and progression, we have elucidated the entire exon/intron structure of the canine p53 gene. A search for p53 gene abnormalities in mammary tumor tissue was undertaken utilizing single strand conformation polymorphism analysis. Mutations were detected in exons 4, 5, 6, and 7 of the p53 gene and consisted of nonsense, splicing, and frameshift mutations. None of 11 benign tumors and 6 of 40 primary carcinomas (15%) were found to harbor subtle p53 mutations. In 14 carcinomas examined the results in primary tumors and metastases were the same. These findings implicate involvement of this gene in the genesis of some malignant canine tumors, in a fashion similar to their human counterparts.

Microsurgical anatomy in China.

This is a general review on the recent advances made in China of microsurgical anatomy. In recent years, more than 300 research papers and a number of monographs on microsurgical anatomy have been published in China. In the research of skin and musculocutaneous flaps, much applied anatomical data about more than 30 new donor areas have been collected and the investigations on the patterns of the blood supply of the flaps are instructively significant to clinical practice. New donor areas have also been introduced for scapular, radial, tibial and other bone flaps, and the range of indications for using the periosteal and cartilaginous flaps has been broadened. On the basis of the technique of superficial lymphaticovenous anastomosis, new information for deep typhaticovenous anastomosis has been provided by clinical anatomists. Through experimental research, the anatomists pointed out that lymphatic vessels with contracting ability should be selected for anastomosis in order to enhance the long term effect of the operation. The successful experiment of bridging the peripheral nerve gap with skeletal muscle, which has been clinically used, has opened up a hopeful prospect for solving the problem of the unavailability of autogenous nerve donors. The identification of nerve fascicles in the nerve trunk provides a morphological basis for the selection of different suture patterns. In addition, much research work has been done on the tranplantation of the suprarenal gland, pancreas, parathyroid gland, testis, kidney of foetus and other small organs.

The ascending branch of the lateral circumflex femoral artery. A new supply for vascularized iliac transplantation.

The ascending branch of lateral circumflex femoral a. was studied in 66 adult limbs in terms of its anatomical description and clinical relevance. The anatomical findings suggest that the ascending branch could be used as an ideal supply for vascularized iliac transplantation. This new technique has been widely used in China since 1984 with satisfactory results.

Applied anatomy of the anterolateral femoral flap.

A study of the source of the blood supply to the anterolateral femoral flap was carried out on 42 lower limbs of adult cadavers (among them 35 cadavers with injection of red latex and 1 with india ink into the arteries and 6 vascular cast specimens), and the surface locations of the vascular pedicle were detected on 50 healthy adults. It was found that the descending branch of the lateral circumflex femoral vessel was an ideal axial vessel. There are constant perforating branches of the myocutaneous artery or cutaneous branches from the intermuscular space to the anterolateral femoral skin. The area extends about 12 x 30 cm. Within the flap, the anterior branch of the anterolateral cutaneous nerve of the high is located. This flap has been widely used for free transplantation in China since 1983 with satisfactory results.

Experimental study of bridging the peripheral nerve gap with skeletal muscle.

A piece of skeletal muscle was used as a conduit to bridge the gap microsurgically between the two ends of the severed sciatic nerve in 30 rats, and a method for histochemical demonstration of acetylcholinesterase was employed to assess the nerve regeneration process 5 weeks or more after the operation. Regenerating nerve fibers were detected in the muscle and could be traced through to the distal stump of the severed sciatic nerve. This suggests that skeletal muscle might serve as a grafting conduit for the repairing of peripheral nerve injuries.