Evaluation of operator radioprotection using a new injection device during vertebroplasty.

This study aimed to evaluate the protection granted by a simple device (X'TENS(®), Thiebaud, France) and to provide operators with information on the performance of this new device, which has not yet been assessed. Our assumption is that this device efficiently reduces the radiation dose to the operator. In a prospective clinical study, the radiation dose the operator's hand receives has been assessed using a specific sensor (UNFOR Instrument). Each patient included in the study was to receive at least two injections of cement during the procedure. Exposure was measured with and without the range extender. The data collected were then processed using a Wilcoxon matched pairs test. During 14 interventions, 20 vertebrae were treated with both procedures. Eleven women and three men were included. Seven patients underwent vertebroplasty for metastatic lesions and seven for osteoporotic lesions, bone fractures or vertebral compressions. The average injection time was 1.35 minutes with the device and 1.20 without (p=0.75). The dose to the hand per ml injected was 111.37 vs. 166.91 (p<0.05). Theoretically, the protection granted by the range extender depends on the length of the device. Our results are consistent with the inverse-square law. However, the variations in our results indicate that a proper and rigorous use is mandatory for the device to be effective. Given that radioprotection during fluoroscopy procedures is a frequently raised issue, the need for information for a safer practice increases likewise.

The lupus family registry and repository.

The Lupus Family Registry and Repository (LFRR) was established with the goal of assembling and distributing materials and data from families with one or more living members diagnosed with SLE, in order to address SLE genetics. In the present article, we describe the problems and solutions of the registry design and biometric data gathering; the protocols implemented to guarantee data quality and protection of participant privacy and consent; and the establishment of a local and international network of collaborators. At the same time, we illustrate how the LFRR has enabled progress in lupus genetics research, answering old scientific questions while laying out new challenges in the elucidation of the biologic mechanisms that underlie disease pathogenesis. Trained staff ascertain SLE cases, unaffected family members and population-based controls, proceeding in compliance with the relevant laws and standards; participant consent and privacy are central to the LFRR's effort. Data, DNA, serum, plasma, peripheral blood and transformed B-cell lines are collected and stored, and subject to strict quality control and safety measures. Coded data and materials derived from the registry are available for approved scientific users. The LFRR has contributed to the discovery of most of the 37 genetic associations now known to contribute to lupus through 104 publications. The LFRR contains 2618 lupus cases from 1954 pedigrees that are being studied by 76 approved users and their collaborators. The registry includes difficult to obtain populations, such as multiplex pedigrees, minority patients and affected males, and constitutes the largest collection of lupus pedigrees in the world. The LFRR is a useful resource for the discovery and characterization of genetic associations in SLE.

Identification of unique microRNA signature associated with lupus nephritis.

MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in peripheral blood mononuclear cells (PBMCs) and Epstein-Barr Virus (EBV)-transformed cell lines obtained from lupus nephritis affected patients and unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. Microarray analysis of miRNA expressed in both African American (AA) and European American (EA) derived lupus nephritis samples revealed 29 and 50 differentially expressed miRNA, respectively, of 850 tested. There were 18 miRNA that were differentially expressed in both racial groups. When samples from both racial groups and different specimen types were considered, there were 5 primary miRNA that were differentially expressed. We have identified 5 miRNA; hsa-miR-371-5P, hsa-miR-423-5P, hsa-miR-638, hsa-miR-1224-3P and hsa-miR-663 that were differentially expressed in lupus nephritis across different racial groups and all specimen types tested. Hsa-miR-371-5P, hsa-miR-1224-3P and hsa-miR-423-5P, are reported here for the first time to be associated with lupus nephritis. Our work establishes EBV-transformed B cell lines as a useful model for the discovery of miRNA as biomarkers for SLE. Based on these findings, we postulate that these differentially expressed miRNA may be potential novel biomarkers for SLE as well as help elucidate pathogenic mechanisms of lupus nephritis. The investigation of miRNA profiles in SLE may lead to the discovery and development of novel methods to diagnosis, treat and prevent SLE.

Bioavailability in healthy adults of efavirenz capsule contents mixed with a small amount of food.

PURPOSE: The effect of mixing the contents of efavirenz capsules (sprinkles) with a small amount of food on the bioavailability and pharmacokinetics of efavirenz in healthy adults was evaluated. METHODS: In a randomized, three-period, crossover study, 24 healthy adult subjects were divided equally into two groups. Group I received treatments A, B, and C, and those in group II received treatments A, D, and E. Treatment A was three efavirenz 200-mg intact capsules under fasting conditions. Treatments B, C, D, and E were three efavirenz 200-mg capsule contents mixed with two teaspoons of applesauce, grape jelly, yogurt, or infant formula, respectively. A single dose was given on days 1, 21, and 41. The steady-state mean maximum observed concentration, time of maximum observed concentration, area under the concentration-time curve (AUC) half-life, taste, and safety were assessed. RESULTS: The AUC after administration of a single 600-mg dose of efavirenz sprinkles mixed with two teaspoons of any of the food vehicles to healthy adults was bioequivalent to a 600-mg efavirenz dose given as intact capsules under fasting conditions. Subjects rated efavirenz mixed with grape jelly as the most palatable. Adverse events and laboratory abnormalities were similar for all treatments. CONCLUSION: The AUC of efavirenz 600 mg administered as capsule sprinkles with two teaspoons of applesauce, grape jelly, yogurt, or infant formula was bioequivalent to a single dose of efavirenz 600 mg given as intact capsules under fasting conditions in healthy adults.

Virologic suppression, treatment adherence, and improved quality of life on a once-daily efavirenz-based regimen in treatment-Naïve HIV-1-infected patients over 96 weeks.

PURPOSE: This study evaluated the long-term efficacy, safety, adherence, and quality of life (QoL) of a once-daily efavirenz-based antiretroviral regimen in two 96-week prospective open-label single-arm studies of treatment-naïve HIV-1-infected patients. METHODS: Patients received once-daily efavirenz 600 mg and lamivudine 300 mg with either enteric-coated didanosine 400 mg (Daily Antiretroviral Therapy trial [DART] I) or extended-release stavudine 100 mg (DART II). The primary efficacy outcome measure was HIV RNA <400 copies/mL at Week 48. RESULTS: In an intent-to-treat (ITT) analysis, HIV RNA level <400 (<50) copies/mL was reached by 82%(80%) and 74% (72%) of patients at Week 48 in DART I and II. At Week 96, the corresponding values were 74% (68%) and 55% (54%), respectively. Both regimens were well tolerated. There were no discontinuations for virologic failure. Medication adherence assessed by pill counts was above 80% in 90% of the patients in DART I and more than 80% of patients in DART II. Treatment produced a significant improvement in overall QoL. CONCLUSION: Once-daily efavirenz-based antiretroviral therapy was effective, durable, and well tolerated. In this study, a high level of adherence was achieved with improvement in overall QoL.

Localization and replication of the systemic lupus erythematosus linkage signal at 4p16: interaction with 2p11, 12q24 and 19q13 in European Americans.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by both population and phenotypic heterogeneity. Our group previously identified linkage to SLE at 4p16 in European Americans (EA). In the present study we replicate this linkage effect in a new cohort of 76 EA families multiplex for SLE by model-free linkage analysis. Using densely spaced microsatellite markers in the linkage region, we have localized the potential SLE susceptibility gene(s) to be telomeric to the marker D4S2928 by haplotype construction. In addition, marker D4S394 showed marginal evidence of linkage disequilibrium with the putative disease locus by the transmission disequilibrium test and significant evidence of association using a family-based association approach as implemented in the program ASSOC. We also performed both two-point and multipoint model-based analyses to characterize the genetic model of the potential SLE susceptibility gene(s), and the lod scores both maximized under a recessive model with penetrances of 0.8. Finally, we performed a genome-wide scan of the total 153 EA pedigrees and evaluated the possibility of interaction between linkage signals at 4p16 and other regions in the genome. Fourteen regions on 11 chromosomes (1q24, 1q42, 2p11, 2q32, 3p14.2, 4p16, 5p15, 7p21, 8p22, 10q22, 12p11, 12q24, 14q12, 19q13) showed evidence of linkage, among which, signals at 2p11, 12q24 and 19q13 also showed evidence of interaction with that at 4p16. These results provide important additional information about the SLE linkage effect at 4p16 and offer a unique approach to uncovering susceptibility loci involved in complex human diseases.

DNA-protein cross-linking via guanine oxidation: dependence upon protein and photosensitizer.

DNA-protein cross-links form when guanine undergoes a 1-electron oxidation in a flash-quench experiment, and the importance of reactive oxygen species, protein, and photosensitizer is examined here. In these experiments, a strong oxidant produced by oxidative quenching of a DNA-bound photosensitizer generates an oxidized guanine base that reacts with protein to form the covalent adduct. These cross-links are cleaved by hot piperidine and are not the result of reactive oxygen species, since neither a hydroxyl radical scavenger (mannitol) nor oxygen affects the yield of DNA-histone cross-linking, as determined via a chloroform extraction assay. The cross-linking yield depends on protein, decreasing as histone > cytochrome c > bovine serum albumin. The yield does not depend on the cytochrome oxidation state, suggesting that reduction of the guanine radical by ferrocytochrome c does not compete effectively with cross-linking. The photosensitizer strongly influences the cross-linking yield, which decreases in the order Ru(phen)(2)dppz(2+) [phen = 1,10-phenanthroline; dppz = dipyridophenazine] > Ru(bpy)(3)(2+) [bpy = 2,2'-bipyridine] > acridine orange > ethidium, in accordance with measured oxidation potentials. A long-lived transient absorption signal for ethidium dication in poly(dG-dC) confirms that guanine oxidation is inefficient for this photosensitizer. From a polyacrylamide sequencing gel of a (32)P-labeled 40-mer, all of these photosensitizers are shown to damage guanines preferentially at the 5' G of 5'-GG-3' steps, consistent with a 1-electron oxidation. Additional examination of ethidium shows that it can generate cross-links between histone and plasmid DNA (pUC19) and that the yield depends on the quencher. Altogether, these results illustrate the versatility of the flash-quench technique as a way to generate physiologically relevant DNA-protein adducts via the oxidation of guanine and expand the scope of such cross-linking reactions to include proteins that may associate only transiently with DNA.