Dysprosium magnesium silicate apatite featuring field and temperature stable slow magnetization relaxation

Dy–Mg silicate Dy₈Mg₂(SiO₄)₆O₂ has been prepared by high-temperature solid state reaction. It has an apatite type structure (P6₃/m) with the Dy atoms fully occupying the 6h site and being in random distribution with the Mg atoms at the 4f site. The compound reveals dual magnetization relaxation with widely varying contributions from fast (FR) and slow (SR) relaxation paths controlled by field and temperature. The SR path is stabilized by a strong magnetic field, exhibits a weak dependence of relaxation time τ on field and temperature, and sustains large τ of a few seconds up to a temperature of 40 K and under a field of 50 kOe. The analysis of the electronic structure and comparison with the known Dy-doped phosphate apatites suggests that the Orbach and Raman processes are suppressed.

The compound reveals dual magnetization relaxation with largely varying contributions from fast and slow relaxation paths controlled by field and temperature. The relaxation times retain values of a few seconds up to 40 K.     

Temporal Trends in Imaging Utilization for Suspected Substance Use Disorder in an Academic Emergency Radiology Department

PurposeTo assess temporal trends and utilization patterns of diagnostic imaging performed for substance use disorder (SUD)-related indications in an academic radiology emergency department (ED).MethodsRetrospective analyses of ED imaging examinations acquired from 2005 to 2015 were performed. Imaging examinations performed for suspected SUD-related indications, based on the order history, were compared with those without a SUD-related indication. Unadjusted analyses comparing demographic and imaging characteristics between SUD-related versus non-SUD-related indications used Wilcoxon and Pearson’s χ² tests. Multivariable logistic regression models, within each imaging modality subgroup and combined, were employed to examine the odds of imaging examinations having an SUD-related indication as a function of demographic and imaging characteristics.ResultsAmong 938,245 examinations, 0.17% had an SUD-related indication. Patients with SUD-related indications were younger (mean 37.2 ± 11.1 versus 53.5 ± 22.4, P < .001) and more commonly male (65% versus 52%, P < .001). The proportions of MR (17%), spine (17%), and extremities (33%) studies performed for SUD-related indications were larger among SUD than non-SUD indications (6%, 8%, 26%, respectively, all P < .001). Regression analysis demonstrated the odds of acquiring an ED imaging examination with an SUD-related indication significantly increased over time (P < .001, adjusted odds ratio [aOR] = 1.06), which was most pronounced among MR (P < .001, aOR = 1.23). For all regression models, younger age, male gender, and body part being imaged were identified as independent predictors of an SUD-related indication for ED imaging.ConclusionImaging performed for an SUD-related indication represented a small but increasing subset of overall ED imaging. Utilization of MR for SUD-related indications significantly outpaced growth of MR without SUD-related indications.     

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C,p.Leu97Pro (hemoglobin Wareham)

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.     

Rapid Delivery of Diazepam from Supersaturated Solutions Prepared Using Prodrug/Enzyme Mixtures: Toward Intranasal Treatment of Seizure Emergencies

Current treatments for seizure emergencies, such as status epilepticus, include intravenous or rectal administration of benzodiazepines. While intranasal delivery of these drugs is desirable, the small volume of the nasal cavity and low drug solubility pose significant difficulties. Here, we prepared supersaturated diazepam solutions under physiological conditions and without precipitation, using a prodrug/enzyme system. Avizafone, a peptide prodrug of diazepam, was delivered with—Aspergillus oryzae (A.O.) protease, an enzyme identified from a pool of hydrolytic enzymes in assay buffer, pH 7.4 at 32°C. This enzyme converted avizafone to diazepam at supersaturated concentrations. In vitro permeability studies were performed at various prodrug/enzyme ratios using Madin-Darby canine kidney II-wild type (MDCKII-wt) monolayers, a representative model of the nasal epithelium. Monolayer integrity was examined using TEER measurement and the lucifer yellow permeability assay. Prodrug/drug concentrations were measured using HPLC. Enzyme kinetics with avizafone-protease mixtures revealed K_M = 1,501 ± 232 μM and V_max = 1,369 ± 94 μM/s. Prodrug-protease mixtures, when co-delivered apically onto MDCKII-wt monolayers, showed 2–17.6-fold greater diazepam flux (S = 1.3–15.3) compared to near-saturated diazepam (S = 0.7). Data for prodrug conversion upstream (apical side) and drug permeability downstream (basolateral side) fitted reasonably well to a previously developed in vitro two compartment pharmacokinetic model. Avizafone-protease mixtures resulted in supersaturated diazepam in less than 5 min, with the rate and extent of supersaturation determined by the prodrug/enzyme ratio. Together, these results suggest that an intranasal avizafone-protease system may provide a rapid and alternative means of diazepam delivery.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9596-5) contains supplementary material, which is available to authorized users.KEY WORDS: avizafone enzyme activation, diazepam delivery, hydrophobic drugs, MDCK monolayers, rapid absorption, seizure emergencies, supersaturation     

Use of BioGlue Surgical Adhesive in Hypospadias Repair

Purpose

To prospectively evaluate the efficacy of albumin glutaraldehyde tissue adhesive (BioGlue) in the surgical treatment of patients with hypospadias.

Materials and Methods

Two groups of 20 patients each who underwent hypospadias repair were included in the study. In the first group we utilized BioGlue as an additional protective layer to the suture line of the neo-urethra, while patients in the second group were operated on utilizing a routine surgical technique.

Results

There were no statistical differences between patients from the 2 groups in terms of surgical complications. Urethrocutaneous fistula was revealed in 4 (20%) patients after repair with BioGlue and in 3 (15%) patients from the control group (p = 0.686), suture line breakdown in 4 (20%) and in 1 (5%) patients (p = 0.478), meatal stenosis in 1 (5%) and in 1 (5%) patient (p = 1). Furthermore more patients in the BioGlue group (n = 12, 60%) demonstrated poor cosmetic results compared to the control group where most patients – 19 (95%) had acceptable cosmetic outcomes (p = 0.007).

Conclusions

Our data showed no benefits of BioGlue use in hypospadias repair.Key Words: Hypospadias, BioGlue, Hypospadias repair, Urethrocutaneous fstula     

Treatment Documentation in Practice-Based Evidence Research for Patients Receiving Physical Therapy Because of Lymphedema

ObjectivesTo describe development and testing of a physical therapy treatment code documentation taxonomy.DesignClinician survey within a practice-based evidence study framework for patients with lymphedema.SettingOutpatient physical therapy clinics within a large public health care service using a central electronic medical record.ParticipantsCertified lymphedema therapists (CLTs) (N=43).InterventionTreatment coding of 10 treatment vignettes representing real-life clinical scenarios. The CLTs were asked to accurately select 35 activity-intervention combination codes.Main Outcome MeasuresThe CLT score represented percentage of treatment codes accurately selected by each therapist. The code score represented percentage of CLTs who accurately selected each treatment code.ResultsThe mean CLT score was 91%, with 72% of CLTs meeting the 90% criterion. Personal feedback was provided to each CLT. The mean code score was also 91%; with 71% of treatment codes meeting the 90% criterion. We identified 9 low-score codes needing additional education or found to be redundant. These codes were either clarified or removed.ConclusionsThe proposed treatment code documentation system for lymphedema therapy was found to be clear and accurately used by most CLTs. Specific needs for improvement were identified. Follow-up testing is warranted to ensure ongoing accurate implementation of the treatment documentation system.     

Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.