Renal calculi: sensitivity for detection with US

The sensitivity of sonography in the detection of renal calculi was tested in a three-phase study in 100 patients. In phase 1, ultrasonographic (US) scanning was performed after review of abdominal radiographs and renal tomograms in 30 patients who had undergone extracorporeal shock wave lithotripsy (ESWL). In this group the sensitivity of US for detecting stones was 98%. In phase 2, scanning was performed in 30 post-ESWL patients without prior review of radiographs or tomograms. The sensitivity of US for stone detection in this group was 95%. In phase 3, sonography was performed in a blinded fashion on a random mix of post-ESWL patients and patients who had undergone urography for reasons unrelated to nephrolithiasis. The sensitivity of US for stone detection in this group of 40 patients was 91%. The overall sensitivity in all three groups was 96%, which was superior to the performance of abdominal radiography and slightly inferior to the combination of abdominal radiography and renal tomography. The ability to detect kidney stones with US depended on stone size but was independent of stone location or patient size. The study findings suggest that US is an effective means for detecting kidney stones in patients with suspected nephrolithiasis.     

Increased vomiting induced by an antiemetic drug

A case of progressive vomiting in a boy aged 5 months is reported. Vomiting was secondary to an obstruction in the antrum of the stomach caused by a mass consisting of alginate.     

Double-strand breaks may initiate the inversion mutation causing the Hunter syndrome

We have previously shown that patients with the Hunter syndrome frequently have suffered from a recombination event between the IDS gene and its putative pseudogene, IDS-2, resulting in an inversion of the intervening DNA. The inversion, which might be the consequence of an intrachromosomal mispairing, is caused by homologous recombination between sequences located in intron 7 of the IDS gene and sequences located distal of exon 3 in IDS-2. In order to gain insight into the mechanisms causing the inversion, we have isolated both inversion junctions in six unrelated patients. DNA sequence analysis of the junctions showed that all recombinations have taken place within a 1 kb region where the sequence identity is >98%. An interesting finding was the identification of regions with alternating IDS gene and IDS-2 sequences present at one inversion junction, suggesting that the recombination event has been initiated by a double-strand break in intron 7 of the IDS gene. The results from this study suggest that homologous recombination in man could be explained by mechanisms similar to those described for Saccharomyces cerevisiae. The results also have practical implications for diagnosis of patients with the Hunter syndrome.      

Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria

Mutation analysis of genomic DNA samples obtained from 17 unrelated South African patients with variegate porphyria (VP) revealed three novel missense mutations in the protoporphyrinogen oxidase (PPOX) gene. A common C to T transition at nucleotide position 452 (R59W) was identified in 15 of the patients analysed, while base changes at positions 336 (H20P) and 779 (R168C) were identified in the remaining two patients. Using protein analysis software we were able to predict that all three mutations have a similar biophysical effect on the protein, being the disturbance of amphiphatic regions within the protein, which might result in misfolding of the protein. Mutation R59W, identified in the majority of South African VP families, was shown to create a Styl restriction site, while mutation R168C would abolish a Dsal restriction site in genomic DNA of affected individuals. As 100% of the index patients analysed were molecularly characterized, the combined use of restriction enzyme and single-strand conformation polymorphism (SSCP) analysis now allows a rapid and accurate diagnosis of VP in South Africa. Mutation R59W was furthermore shown to be in association with one of four potential haplotypes defined by two newly described polymorphisms in exon 1 of the PPOX gene. Our molecular data thus strongly support the founder hypothesis for VP in South Africa.