Citations

Abstract To gain insights into 1,25-dihydroxyvitamin D3 receptor (VDR) function during fetal bone development, we examined fetal rat tissues from gestational days 13–21 for the presence and distribution of VDR using immuno-histochemistry. Prior to ossification, VDR epitopes were observed in the mesenchyme condensing to form skeletal tissues, on day 13 in the developing vertebral column and limbs, and on day 17 of gestation in developing calvaria. Immunostaining for VDR was seen in proliferating and hypertrophic chondrocytes and in osteoblasts of limb buds and the vertebral column by day 17 of gestation. In calvaria, VDR epitopes were observed in osteoblasts by gestational day 19. VDR immunostaining was also evident in the skin of fetal limbs at all gestational ages examined. We show for the first time that the VDR appears very early in the developing fetal rat skeleton, suggesting that the VDR, in concert with its ligand, 1,25-dihydroxyvitamin D3, may play a role in the differentiation of mesenchymal precursors into bone tissue.

Abstract Vertebral fractures are the classic hallmark of osteoporosis, yet little is known of their epidemiology. The incidence of clinically diagnosed vertebral fractures was therefore directly assessed in the predominantly white (European descent) population of Rochester, Minnesota. Altogether, 341 Rochester residents were radiologically diagnosed for the first time with one or more vertebral fractures in the 5 year study period, 1985–1989. The overall age- and sex-adjusted incidence rate was 117 per 100,000 person-years (95% CI, 105 to 130). The age-adjusted rate in women (145 per 100,000 person-years) was almost twice that in men (73 per 100,000 person-years). Of all fractures, 47 (14%) followed severe trauma, 282 (83%) followed moderate or no trauma, and 12 (3%) were pathologic. Incidence rates for fractures following moderate trauma were higher in women than in men and rose steeply with age in both genders. In contrast, fractures following severe trauma were more frequent in men, and their incidence increased less with age. These Rochester rates are greater than those previously reported from studies in Britain and Sweden but lower than the incidence rates extrapolated from a prevalence study in this population.

Background Treatment of the multiligament-injured knee remains controversial. Purpose To compare clinical and functional outcomes of a consecutive series of multiligament-injured knees that underwent repair of the fibular collateral ligament (FCL) and posterolateral corner (PLC), followed by delayed cruciate ligament reconstructions, with those that had single-stage multiligament reconstruction. Study Design Cohort study; Level of evidence, 3. Methods Patients with multiligament knee injury treated by a single surgeon were identified in our prospective database. Between February 2004 and May 2005, patients underwent repair of medial- and lateral-sided injuries, followed by delayed cruciate ligament reconstructions. Between May 2005 and February 2007, patients underwent single-stage multiligament knee reconstruction. All patients followed a standard rehabilitation protocol. Inclusion criteria were minimum 2-year follow-up and multiligament knee injury including the FCL/PLC. International Knee Documentation Committee subjective and Lysholm scores and objective clinical data were documented. Results We identified 45 knees (42 patients); 17 knees (14 patients) were excluded, leaving 28 knees (28 patients) in the study. The repair/staged group (10 knees in 10 patients) had a mean follow-up of 34 months (range, 24-49 months). The reconstruction group (18 knees in 18 patients) had a mean follow-up of 28 months (range, 24-41 months). Four of the 10 FCL/PLC repairs (40%) and 1 of the 18 FCL/PLC reconstructions (6%) failed (P = .04). After revision reconstructions, there were no statistically significant differences between mean International Knee Documentation Committee subjective scores (79 vs. 77, P = .92) and mean Lysholm scores (85 vs 88, P = .92). Regression analysis showed no effect on failure based on age, sex, injury mechanism, time to surgery, interval between stages, total number of ligaments injured, or location of tear. Conclusion Our series demonstrated a statistically significant higher rate of failure for repair compared with reconstruction of the FCL/PLC. Reconstruction of the FCL/PLC structures is a more reliable option than repair alone in the setting of a multiligament knee injury.

Acute ischemic insults to the kidney are recognized complications of human sickle cell disease (SCD). The present study analyzed in a transgenic SCD murine model the early renal response to acute ischemia. Renal hemodynamics were profoundly impaired following ischemia in sickle mice compared with wild-type mice: glomerular filtration rate, along with renal plasma flow and blood flow rates, were markedly reduced, while renal vascular resistances were increased more than threefold in sickle mice following ischemia. In addition to these changes in renal hemodynamics, there were profound disturbances in renal signaling processes: phosphorylation of members of the MAPK and Akt signaling proteins occurred in the kidney in wild-type mice after ischemia, whereas such phosphorylation did not occur in the kidney in sickle mice after ischemia. ATP content in the postischemic kidney in sickle mice was less than half that observed in wild-type mice. Examination of the expression of candidate genes uncovered changes that may predispose to increased sensitivity of the kidney in sickle mice to ischemia: increased expression of inducible nitric oxide synthase and decreased expression of endothelial nitric oxide synthase, and increased expression of TNF-α. Inducibility of anti-inflammatory, cytoprotective genes, such as heme oxygenase-1 and IL-10, was not impaired in sickle mice after ischemia. We conclude that the kidney in SCD is remarkably vulnerable to acute ischemic insults. We speculate that such sensitivity of the kidney to ischemia in SCD may underlie the occurrence of acute kidney injury in patients with SCD and may set the stage for the emergence of chronic kidney disease in SCD.

ABSTRACT No significantly discordant results were observed between the Abbott RealTi m e HIV-1 assay and the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (CTM) among 1,190 unique clinical plasma specimens obtained from laboratories located in 40 states representing all nine U.S. geographic regions and previously yielding “target not detected” results by CTM.

Purpose This study’s main purpose was to (a) identify acoustic signatures of hypokinetic dysarthria (HKD) that are robust to phonetic variation in conversational speech and (b) determine specific characteristics of the variability associated with HKD. Method Twenty healthy control (HC) participants and 20 participants with HKD associated with idiopathic Parkinson’s disease (PD) repeated 3 isolated sentences (controlled phonetic content) and 2 min of conversational speech (phonetic content treated as a random variable). A MATLAB-based program automatically calculated measures of contrastivity: speech–pause ratio, intensity variation, median and maximum formant slope, formant range, change in the upper and lower spectral envelope, and range of the spectral envelope. t tests were used to identify which measures were sensitive to HKD and which measures differed by task. Discriminant analysis was used to identify the combination of measures that best predicted HKD, and this analysis was then used as a general measure of contrastivity (Contrastivity Index). Differential effects of HKD on maximum and typical contrastivity levels were tested with interaction of maximum, minimum, and median observations of individual speakers and with pairwise comparisons of skewness and kurtosis of the contrastivity index distributions. Results Group differences were detected with pairwise comparisons with t tests in 8 of the 9 measures. Percentage pause time and spectral range were identified as the most specific (95%) and accurate (95%) differentiators of HKD and HC conversational speech. Sentence repetition elicited significantly higher levels of contrastivity than conversational speech in both HC and HKD speakers. Maximum and minimum contrastivities were significantly lower in HKD speech, but there was no evidence that HKD affects maximum contrastivity levels more than median contrastivity levels. The HKD speakers' contrastivity distributions were significantly more skewed to lower levels of production. Conclusion HKD can be consistently distinguished from HC speech in both sentence repetition and conversational speech on the basis of intensity variation and spectral range. Although speakers with HKD were effectively able to produce higher contrastivity levels in sentence repetition tasks, they habitually performed closer to the lower end of their production ranges.

Published literature have not discerned end-of-life palliative versus life-shortening effects of pharmacologically maintaining continuous deep sedation until death (ie, dying in deep sleep) compared with common sedation practices relieving distress in the final conscious phase of dying. Continuous deep sedation predictably suppresses brainstem vital centers and shortens life. Continuous deep sedation remains controversial as palliation for existential suffering and in elective death requests by discontinuation of chronic ventilation or circulatory support with mechanical devices. Continuous deep sedation contravenes the double-effect principle because: (1) it induces permanent coma (intent of action) for the contingency relief of suffering and for social isolation (desired outcomes) and (2) because of its predictable and proportional life-shortening effect. Continuous deep sedation should be distinguished from common sedation practices for palliation and characterized instead as physician-assisted death.