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Timed urine collections are a standard part of the evaluation for predisposition to stone formation in children with urolithiasis. Supersaturation is defined as the ratio of the concentration of dissolved salt to its solubility in urine. The purpose of the present study was to determine if adding supersaturation to the standard timed urine collection increased the ability to detect a metabolic predisposition to stone formation. Thirty-two children with urolithiasis had 24-hour urine measurements of calcium, oxalate, citrate, uric acid, and cystine (the "traditional" evaluation), as well as supersaturation for calcium oxalate, calcium phosphate, and uric acid, on the same urine sample. Nine (28%) of the 32 were hypercalciuric, 2 (6%) hyperoxaluric, and 4 (12%) hypocitraturic. In total, 14 (44%) had a metabolic predisposition that was detected by the traditional evaluation. Supersaturation was elevated in 18 (56%), including nine who did not have metabolic predisposition detected by traditional evaluation. Urine volume was low in 17 (53%) of 32 children, including eight of nine children with abnormal supersaturation but normal traditional evaluation. Only one child with normal traditional evaluation and normal urine volume had elevated supersaturation. These results show that the benefit of adding supersaturation to the traditional evaluation was largely negated by consideration of urine volume.

Faculty and residents had discordant perceptions of resident autonomy and of faculty support for resident autonomy. When faculty restrict the independence of "passive" residents whose competence they question, residents may receive fewer opportunities for active learning. Strategies that support autonomy, such as scaffolding, may help residents gain confidence and competence, enhance residents' relatedness to team members and supervisors, and help programs adapt to accreditation requirements to foster residents' growth in independence.

Translationally silent mutations, which are not antigen selected, of human VH6 Ig gene rearrangements isolated from human spleen were analyzed for bias to gain insight into intrinsic features of the mutation process. Sixty-three clones representing 38 VH6DJ rearrangements had an overall mutation frequency of 4.5%, a replacement/silent (R/S) mutation ratio of 2.1 and 167 unique silent mutations. The silent mutations showed bias in: (i) targeting to CDR1 and CDR2, (ii) an increased frequency of mutations of A compared to T nucleotide bases on the coding strand, and (iii) an increased frequency of transitions versus transversions. Bias of C-->G over C-->A, of G-->C over G-->T and of A-->C over A-->T transversions was also present. Hot spots of mutation were observed, some which corresponded to potential sites of stem-loop formation. The results suggest that the somatic mutation process in man may be targeted to the complementarity determining region for some V genes, exhibits specific base substitutions favoring transitions and specific types of transversions, and may be occurring on only one DNA strand.

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To study inherent properties of somatic hypermutation of human immunoglobulin genes in the absence of antigen selection, mutations of human non-productive VH6 rearrangements enriched by subtractive hybridization were characterized. Ten unique clones arising from nine non-productive rearrangements were isolated. The frequency of mutation was 3.0%. Analysis of these mutations showed intrinsic bias for transitions and cytosine (C) to guanine (G) and G to C transversions. Bias for the strand of DNA targeted by mutation was not evident. Replacement mutations in the complementarity-determining region (CDR) occurred more frequently than expected based on the primary DNA sequence. This targeting of replacement mutations to the CDR may explain the conservation of the VH6 sequence in primates.