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Leri–Weill dyschondrosteosis (LWD) results from heterozygous mutations of the SHOX gene, with homozygosity or compound heterozygosity resulting in the more severe form, Langer mesomelic dysplasia (LMD). These mutations typically take the form of whole or partial gene deletions, point mutations within the coding sequence, or large (>100?kb) 3? deletions of downstream regulatory elements. We have analyzed the coding sequence of the SHOX gene and its downstream regulatory regions in a cohort of 377 individuals referred with symptoms of LWD, LMD or short stature. A causative mutation was identified in 68% of the probands with LWD or LMD (91/134). In addition, a 47.5?kb deletion was found 160?kb downstream of the SHOX gene in 17 of the 377 patients (12% of the LWD referrals, 4.5% of all referrals). In 14 of these 17 patients, this was the only potentially causative abnormality detected (13 had symptoms consistent with LWD and one had short stature only), but the other three 47.5?kb deletions were found in patients with an additional causative SHOX mutation (with symptoms of LWD rather than LMD). Parental samples were available on 14/17 of these families, and analysis of these showed a more variable phenotype ranging from apparently unaffected to LWD. Breakpoint sequence analysis has shown that the 47.5?kb deletion is identical in all 17 patients, most likely due to an ancient founder mutation rather than recurrence. This deletion was not seen in 471 normal controls (P?0.0001), providing further evidence for a phenotypic effect, albeit one with variable penetration.

Prompt administration of intravenous (i.v.) dantrolene sodium (DS) is the primary determinant of successful treatment of malignant hyperthermia (MH) syndrome. Because DS has a long reconstitution time for use in treating an MH crisis, we evaluated an alternative technique for hastening the reconstitution. Simulating real-world conditions, with equipment common to the operating room environment, we conducted a randomized, controlled, single-blind study dividing 16 DS vials into 2 equal groups: warm (41 degrees C) and ambient temperature (22 degrees C). With an i.. fluid warmer at 41 degrees C, primed with a 1-L bag of preservative-free sterile water, attached to a 60-mL syringe via a 3-way stopcock, we aspirated and injected the diluent directly into each DS vial. The Icarus effect was clearly demonstrated: warmed diluent vs ambient temperature hastened the reconstitution time for DS. The mean time to particulate-free DS solution suitable for i.v. injection with the warm diluent was 58.88 seconds compared with 93.87 seconds for the ambient temperature group (P.001). A practical method using a reliable and safe warming device readily available to anesthetists and ubiquitous to the operating room environment speeds the time to administration of DS ultimately reducing morbidity and mortality associated with MH.

One hundred twenty-four women with chronic, persistent lower urinary tract symptoms who had been scheduled for elective urodynamic investigations at Mount Sinai's Urodynamic Investigative Unit were divided into two blind, randomized groups, receiving either a placebo or prophylactic antibiotic. At the time of urodynamic testing, the rate of unsuspected urinary tract infection was 8.1 %. There was no statistically significant decrease in postinstrumentation infection rate in the group who received prophylactic antibiotics. We conclude that, given in the fashion described in the study, prophylactic antibiotics are not effective in preventing urinary tract infections caused by urodynamic testing.