Dimercaptosuccinic acid scan or ultrasound in screening for vesicoureteral reflux among children with urinary tract infections.

BACKGROUND: There is considerable interest in detecting vesicoureteral reflux (VUR) because its presence, especially when severe, has been linked to an increased risk of urinary tract infections and renal scarring. Voiding cystourethrography (VCUG), also known as micturating cystourethrography, is the gold standard for the diagnosis of VUR, and the grading of its severity. Because VCUG requires bladder catheterisation and exposes children to radiation, there has been a growing interest in other screening strategies that could identify at-risk children without the risks and discomfort associated with VCUG. OBJECTIVES: The objective of this review is to evaluate the accuracy of two alternative imaging tests - the dimercaptosuccinic acid renal scan (DMSA) and renal-bladder ultrasound (RBUS) - in diagnosing VUR and high-grade VUR (Grade III-V VUR). SEARCH METHODS: We searched MEDLINE, EMBASE, BIOSIS, and the Cochrane Register of Diagnostic Test Accuracy Studies from 1985 to 31 March 2016. The reference lists of relevant review articles were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We considered published cross-sectional or cohort studies that compared the results of the index tests (DMSA scan or RBUS) with the results of radiographic VCUG in children less than 19 years of age with a culture-confirmed urinary tract infection. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate summary sensitivity and specificity values. MAIN RESULTS: A total of 42 studies met our inclusion criteria. Twenty studies reported data on the test performance of RBUS in detecting VUR; the summary sensitivity and specificity estimates were 0.44 (95% CI 0.34 to 0.54) and 0.78 (95% CI 0.68 to 0.86), respectively. A total of 11 studies reported data on the test performance of RBUS in detecting high-grade VUR; the summary sensitivity and specificity estimates were 0.59 (95% CI 0.45 to 0.72) and 0.79 (95% CI 0.65 to 0.87), respectively. A total of 19 studies reported data on the test performance of DMSA in detecting VUR; the summary sensitivity and specificity estimates were 0.75 (95% CI 0.67 to 0.81) and 0.48 (95% CI 0.38 to 0.57), respectively. A total of 10 studies reported data on the accuracy of DMSA in detecting high-grade VUR. The summary sensitivity and specificity estimates were 0.93 (95% CI 0.77 to 0.98) and 0.44 (95% CI 0.33 to 0.56), respectively. AUTHORS' CONCLUSIONS: Neither the renal ultrasound nor the DMSA scan is accurate enough to detect VUR (of all grades). Although a child with a negative DMSA test has an < 1% probability of having high-grade VUR, performing a screening DMSA will result in a large number of children falsely labelled as being at risk for high-grade VUR. Accordingly, the usefulness of the DMSA as a screening test for high-grade VUR should be questioned.

An o-aminoanilide analogue of 1α,25-dihydroxyvitamin D(3) functions as a strong vitamin D receptor antagonist.

Vitamin D receptor (VDR) antagonists have therapeutic potential in treatment of allergic conditions and hypercalcemia driven by granulomatous diseases. We have identified an o-aminoanilide analogue of the hormonal form of vitamin D with a dienyl side chain that functions as a strong VDR antagonist. Modeling studies indicate that antagonism arises from side chain rigidity, when compared to a more flexible saturated analogue, which interferes with H12 folding/alignment.

Vitamin D receptor agonist/histone deacetylase inhibitor molecular hybrids.

Incorporation of zinc-binding groups into the side-chain of 1alpha,25-dihydroxyvitamin D(3) (1,25D) fully bifunctional hybrid molecules which act both as vitamin D receptor agonists and histone deacetylase inhibitors. These bifunctional hybrids display in vitro antiproliferative activity against the AT84 squamous carcinoma cell line while lacking the in vivo hypercalcemic effects of 1,25D.