Performance and comparison of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population.

AIMS: Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. METHODS: A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. RESULTS: The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. CONCLUSIONS: These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.     

Late atrioventricular block after heart transplantation.

Bradyarrhythmia requiring permanent pacing after heart transplantation remains a common problem. Sinus node dysfunction is the most common indication, and late onset of atrioventricular (AV) block has rarely been reported. We report the case of a patient who developed advanced AV block at 41 months after transplantation. Right bundle branch block with progressive increase of QRS complex duration was noted in serial electrocardiograms. At the time of late AV block development, the patient did not have acute rejection and coronary angiogram was normal. The mechanism of late onset of AV block is unclear, but it may be caused by progressive conduction.     

Radiographic manifestations and pathologic basis of parosteal osteosarcoma. Analysis of 17 cases.

The authors reviewed the radiographic manifestations of 17 cases of parosteal osteosarcoma, with pathologic correlation in 15. There were two types of parosteal osteosarcoma radiologically. The majority of cases were type I with uniformly dense masses which had regular borders. They often adhered to the cortex and showed no evidence of soft-tissue invasion which correlated with low-grade pathologic malignancy and a relatively benign clinical course. Type II involved the bone, soft-tissue and the medullary cavity. These lesions were poorly differentiated and frequently accompanied by metastatic lesions.

     

Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450.

The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered in the clinic as a racemic mixture of R-IFA and S-IFA. Hepatic cytochrome P450 (P450) enzymes exhibit enantioselective preferences in the metabolism of R-IFA and S-IFA; however, the impact of this selectivity on P450-dependent anticancer activity is not known. Presently, the metabolism and cytotoxicity of R-IFA and S-IFA were determined in 9L gliosarcoma and Chinese hamster ovary tumor cells expressing an IFA-activating P450 enzyme and by in vitro steady-state kinetic analysis using cDNA-expressed P450 enzymes. Tumor cells expressing P450 enzyme CYP3A4 were the most sensitive to R-IFA cytotoxicity, whereas tumor cells expressing CYP2B1 or CYP2B6 were most sensitive to cyclophosphamide (CPA), an isomer of IFA. Correspondingly, CYP3A4-expressing cells and cDNA-expressed CYP3A4 metabolized R-IFA to yield the active, 4-hydroxylated metabolite at a 2- to 3-fold higher rate than they metabolized S-IFA or CPA. CYP2B cells and cDNA-expressed CYP2B enzymes metabolized CPA almost exclusively by 4-hydroxylation, whereas R-IFA and S-IFA were substantially converted to inactive, N-dechloroethylated metabolites. Further investigation revealed that CYP3A1, a rat enzyme, exhibited superior kinetic properties compared with the human enzyme CYP3A4, with R-IFA and S-IFA both metabolized with high catalytic efficiency by 4-hydroxylation and with a K(m) value of 200 microM, approximately 5-fold lower than CYP3A4. Based on these kinetic parameters and metabolic profiles, R-IFA is expected to exert greater anticancer activity than S-IFA or CPA against tumors that express CYP3A enzymes, whereas tumors expressing CYP2B enzymes may be more sensitive to CPA treatment.     

The influence of some non-steroidal anti-inflammatory drugs on the retraction of collagen lattices.

The effects of some antirheumatics on the formation and retraction of collagen lattices seeded with fibroblasts have been studied. Among the antirheumatics, diclofenac was the most active inhibitor of lattice retraction, then tropesin and to a lesser extent indomethacin. Ibuprofen which is known as a very slight inhibitor of protein synthesis was able to significantly enhance lattice retraction when 10 micrograms/ml (48.5 microM) and 50 micrograms/ml (242 microM) were used.