Clinical Nomograms to Predict Stone-Free Rates after Shock-Wave Lithotripsy: Development and Internal-Validation

Purpose

Shock-wave lithotripsy (SWL) is accepted as the first line treatment modality for uncomplicated upper urinary tract stones; however, validated prediction models with regards to stone-free rates (SFRs) are still needed. We aimed to develop nomograms predicting SFRs after the first and within the third session of SWL. Computed tomography (CT) information was also modeled for constructing nomograms.

Materials and Methods

From March 2006 to December 2013, 3028 patients were treated with SWL for ureter and renal stones at our three tertiary institutions. Four cohorts were constructed: Total-development, Total-validation, CT-development, and CT-validation cohorts. The nomograms were developed using multivariate logistic regression models with selected significant variables in a univariate logistic regression model. A C-index was used to assess the discrimination accuracy of nomograms and calibration plots were used to analyze the consistency of prediction.

Results

The SFR, after the first and within the third session, was 48.3% and 68.8%, respectively. Significant variables were sex, stone location, stone number, and maximal stone diameter in the Total-development cohort, and mean Hounsfield unit (HU) and grade of hydronephrosis (HN) were additional parameters in the CT-development cohort. The C-indices were 0.712 and 0.723 for after the first and within the third session of SWL in the Total-development cohort, and 0.755 and 0.756, in the CT-development cohort, respectively. The calibration plots showed good correspondences.

Conclusions

We constructed and validated nomograms to predict SFR after SWL. To the best of our knowledge, these are the first graphical nomograms to be modeled with CT information. These may be useful for patient counseling and treatment decision-making.     

ELECTRON MICROSCOPY OF ABSORPTION OF TRACER MATERIALS BY TOAD URINARY BLADDER EPITHELIUM

The absorption of Thorotrast and saccharated iron oxide by the epithelium of the toad urinary bladder was studied by electron microscopy. Whether the toads were hydrated, dehydrated, or given Pitressin, no significant differences in transport of colloidal particles by epithelial cells were observed. This implies that these physiological factors had little effect on the transport of the tracer particles. Tracer particles were encountered in three types of epithelial cells which line the bladder lumen, but most frequently in the mitochondria-rich cells. Tracer materials were incorporated into the cytoplasm of epithelial cells after being adsorbed to the coating layer covering the luminal surface of the cells. In the intermediate stage (1 to 3 hours after introducing tracer) particles were present in small vesicles, tubules, and multivesicular bodies. In the later stages (up to 65 hours), the particles were more commonly seen to be densely packed within large membrane-bounded bodies which were often found near the Golgi region. These large bodies probably were formed by the fusion of small vesicles. Irrespective of the stages of absorption, no particles were found in the intercellular spaces or in the submucosa. Particles apparently did not penetrate the intercellular spaces of the epithelium beyond the level of the tight junction.     

Unique structure in the intergenic and 5' external transcribed spacer of the ribosomal RNA gene from the pea aphid Acyrthosiphon pisum.

We analyzed the DNA sequence of the 5' external transcribed spacer (ETS) and part of the intergenic transcribed spacer (IGS) of the aphid ribosomal RNA gene (rDNA). The 5' ETS of aphid rDNA consists of 843 nucleotides with a G/C content of 69 mol/100 mol, far higher than that of any other known 5' ETS for insect rDNA. The IGS of aphid rDNA contained a characteristic array of repeated sequences of 247 nucleotides. The repeated sequences were identical. It was shown that the number of the repeating sequence is heterogeneous.     

Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease

The sulfatide activator protein, also known as SAP-1, is derived from a gene that generates an mRNA coding for four homologous proteins. Its physiological function is to stimulate hydrolysis of sulfatide by arylsulfatase A in vivo. A genetic defect in the sulfatide activator results in a metabolic disorder similar to classical metachromatic leukodystrophy, which is itself caused by a genetic defect in arylsulfatase A. In a patient with sulfatide activator deficiency, a nucleotide transversion G722----C (counted from A of the initiation codon ATG) was found in the mRNA of the sulfatide activator precursor, resulting in the substitution of serine for Cys241 in the mature sulfatide activator. The remainder of the coding sequence was completely normal except for a polymorphism C to T in position 1389, which does not change the amino acid sequence. The patient produces at least three different forms of mRNA for the precursor. Two of them include a stretch of an additional 9 and 6 bases, respectively, within the sulfatide activator coding region. In normal individuals this stretch of additional bases has also been observed. This could be explained by the presence of a small 9-base pair exon which can be introduced, or not, by alternative splicing as a stretch of 9 or 6 bases into the mature mRNA. The shortest form of the mRNA yields an active sulfatide activator (Fürst, W., Schubert, J., Machleidt, W., Meier, H. E., and Sandhoff, K. (1990) Eur. J. Biochem. 192, 709-714).     

Chemical modification ofPseudomonas fluorescens malonyl-CoA synthetase by diethylpyrocarbonate: Kinetic evidence for an essential histidyl residue on alpha subunit

Malonyl-CoA synthetase fromPseudomonas fluorescens was inactivated by diethylpyrocarbonate (DEP) with the second-order rate constant of 775 M^?1 min^?1 atpH 7.0, 25°C, showing a concomitant increase in absorbance at 242 nm due to the formation of N-carbethoxyhistidyl derivatives. The inactivated enzyme at low concentration of DEP (<0.2 mM) could be completely reactivated by hydroxylamine but not completely reactivated at high concentration (>0.5 mM), indicating that there may be another functional group modified by DEP. Complete inactivation of malonyl-CoA synthetase required the modification of seven residues per molecule of enzyme; however, only one is calculated to be essential for enzyme activity by a statistical analysis of the residual enzyme activity.pH dependence of inactivation indicated the involvement of a residue with apK _a of 6.7, which is closely related to that of histidyl residue of proteins. Whena subunit treated with DEP was mixed with β subunits complex, the enzyme activity completely disappeared, whereas when β subunit complex treated with the reagent was mixed witha subunit, the activity remained. Inactivation of the enzyme by the reagent was protected by the presence of malonate and ATP. These results indicate that a catalytically essential histidyl residue is located at or near the malonate and ATP binding region ona subunit of the enzyme.