bluuebunny/crossref_metadata_2025 huggingface dataset:
Power of Tests for a Dichotomous Independent Variable Measured with Error
Authors: McCaffrey Daniel F. , Elliott Marc N.
Published: May 2008

Objective.To examine the implications for statistical power of using predicted probabilities for a dichotomous independent variable, rather than the actual variable.

Data Sources/Study Setting.An application uses 271,479 observations from the 2000 to 2002 CAHPS Medicare Fee‐for‐Service surveys.

Study Design and Data.A methodological study with simulation results and a substantive application to previously collected data.

Principle Findings.Researchers often must employ key dichotomous predictors that are unobserved but for which predictions exist. We consider three approaches to such data: theclassification estimator(1); thedirect substitution estimator(2); thepartial information maximum likelihood estimator(3, PIMLE). The efficiency of (1) (its power relative to testing with the true variable) roughly scales with the square of one less the classification error. The efficiency of (2) roughly scales with theR2for predicting the unobserved dichotomous variable, and is usually more powerful than (1). Approach (3) is most powerful, but for testing differences in means of 0.2–0.5 standard deviations, (2) is typically more than 95 percent as efficient as (3).

Conclusions.The information loss from not observing actual values of dichotomous predictors can be quite large. Direct substitution is easy to implement and interpret and nearly as efficient as the PIMLE.
Medicaid Managed Care and the Unmet Need for Mental Health Care among Children with Special Health Care Needs
Authors: Tang Michael H. , Hill Kristen S. , Boudreau Alexy A. , Yucel Recai M. , Perrin James M. , Kuhlthau Karen A.
Published: May 2008

Objective. To determine the association between Medicaid managed care pediatric behavioral health programs and unmet need for mental health care among children with special health care needs (CSHCN).

Data Source. The National Survey of CSHCN (2000–2002), using subsets of 4,400 CSHCN with Medicaid and 1,856 CSHCN with Medicaid and emotional problems. Additional state‐level sources were used.

Study Design. Multilevel models investigated the association between managed care program type (carve‐out, integrated) or fee‐for‐service (FFS) and reported unmet mental health care need.

Data Collection/Extraction Methods. The National Survey of CSHCN conducted telephone interviews with a sample representative at both the national and state levels.

Principal Findings. In multivariable models, among CSHCN with only Medicaid, living in states with Medicaid managed care (odds ratio [OR]=1.81; 95 percent confidence interval: 1.04–3.15) or carve‐out programs (OR=1.93; 1.01–3.69) were associated with greater reported unmet mental health care need compared with FFS programs. Among CSHCN on Medicaid with emotional problems, the association between managed care and unmet need was stronger (OR=2.48; 1.38–4.45).

Conclusions. State Medicaid pediatric behavioral health managed care programs were associated with greater reported unmet mental health care need than FFS programs among CSHCN insured by Medicaid, particularly for those with emotional problems.
Role of State Policies in the Adoption of Naltrexone for Substance Abuse Treatment
Authors: Heinrich Carolyn J. , Hill Carolyn J.
Published: May 2008

Objective. To examine state policies associated with adoption of a pharmaceutical agent—naltrexone—by substance abuse treatment facilities to treat alcohol‐dependent clients.

Data Sources. Facility‐level data from the 2003 National Survey of Substance Abuse Treatment Services, and state‐level data on policy and environmental factors from publicly available sources.

Study Design. We use facility‐ and state‐level data in a cross‐sectional, multilevel model to analyze state‐level policies that are associated with treatment facilities' naltrexone adoption.

Data Collection/Extraction Methods. The analysis uses survey data.

Principal Findings. State Medicaid policies supporting the use of generic drugs, reducing drug costs, and permitting managed care organizations to establish policies encouraging use of generics were associated with higher odds of naltrexone adoption (by up to 96 percent). State policies limiting access to pharmaceutical technologies through Medicaid preferred drug lists, restricting access to pharmacy networks, and imposing general limitations on use of Medicaid benefits for rehabilitation for substance abuse treatment were associated with reduced odds of naltrexone adoption.

Conclusions. Policy levers that are available to state governments are associated with the adoption of pharmaceutical technologies such as naltrexone that could help meet widespread need for access to clinically proven and cost‐effective treatments for substance abuse.
Voxel‐based 3D MRI analysis helps to detect subtle forms of subcortical band heterotopia
Authors: Huppertz Hans‐Jürgen , Wellmer Jörg , Staack Anke Maren , Altenmüller Dirk‐Matthias , Urbach Horst , Kröll Judith
Published: May 2008

Summary

Purpose: To evaluate the potential diagnostic value of a novel magnetic resonance image (MRI) postprocessing technique in subtle forms of subcortical band heterotopia (SBH). The method was introduced to improve the visualization of blurred gray–white matter junctions associated with focal cortical dysplasia but was found to be applicable also to SBH.

Methods: In the voxel‐based MRI analysis presented here, T1‐weighted MRI volume data sets are normalized and segmented using standard algorithms of SPM5. The distribution of gray and white matter is analyzed on a voxelwise basis and compared with a normal database of 150 controls. Based on this analysis, a three‐dimensional feature map is created that highlights brain areas if their signal intensities fall within the range between normal gray and white matter and differ from the normal database in this respect. The method was applied to the MRI data of 378 patients with focal epilepsy in three different epilepsy centers.

Results: SBH was diagnosed in seven patients with five of them showing subtle forms of SBH that had gone unrecognized in conventional visual analysis of MRI and were only detected by MRI postprocessing. In contrast to distinct double cortex syndrome, these patients had partial double cortex with SBH mostly confined to posterior brain regions.

Conclusions: The results of this study suggest that a considerable part of cases with SBH might remain unrecognized by conventional MRI. Voxel‐based MRI analysis may help to identify subtle forms and appears to be a valuable additional diagnostic tool in the evaluation of patients with cryptogenic epilepsy.
Altered spatial distribution of PV‐cortical cells and dysmorphic neurons in the somatosensory cortex of BCNU‐treated rat model of cortical dysplasia
Authors: Moroni Ramona Frida , Inverardi Francesca , Regondi Maria Cristina , Panzica Ferruccio , Spreafico Roberto , Frassoni Carolina
Published: May 2008

Summary

Purpose:Cortical dysplasia (CD) represents a wide range of histopathological abnormalities of the cortical mantle that are frequently associated with drug‐resistant epilepsy. Recently, carmustine (1‐3‐bis‐chloroethyl‐nitrosurea [BCNU]), given to pregnant rats on embryonic day (E) 15, has been used to develop an experimental model mimicking human CD. The aim of this study was to characterize cytological and histological alterations in this model, and compare the results with those observed in human CD.

Methods:Pregnant rats were given intraperitoneal injections of BCNU on E15. Sections of cerebral cortex from adult BCNU‐treated rats were cytoarchitecturally and immunohistochemically analyzed using anti‐SMI311, anticalbindin (CB), and antiparvalbumin (PV) antibodies. The density of the PV‐immunoreactive (PV‐ir) interneurons was quantitatively assessed by means of a two‐dimensional cell‐counting technique, and the spatial distribution of PV‐ir neurons was evaluated by using the Voronoi tessellation.

Results:The morphological features included reduced cortical size, laminar disorganization, and heterotopic clusters of neurons. We also identified large, disoriented SMI311‐positive pyramidal neurons, and dysmorphic neurons intensely immunostained for neurofilaments, similar to those observed in human dysplastic cortex. An altered distribution of PV‐immunoreactive cortical interneurons was also present.

Conclusions:Although some of the cytoarchitectural abnormalities found in BCNU‐exposed cortex are similar to those found in other CD models, we identified new alterations that recall the neuropathological description of type IIA (Taylor's type) CD. BCNU‐treated rat could therefore be a useful additional model for investigating the pathogenic mechanisms involved in this CD.
Age‐dependent cyclooxygenase‐2 induction and neuronal damage after status epilepticus in the postnatal rat hippocampus
Authors: Järvelä Juha T. , Lopez‐Picon Francisco R. , Holopainen Irma E.
Published: May 2008

Summary

Purpose: Epileptic seizures lead to age‐dependent neuronal damage in the developing brain, particularly in the hippocampus, but the mechanisms involved have remained poorly elucidated. In this study, we investigated the contribution of apoptosis and inflammatory processes to neuronal damage after status epilepticus (SE) in postnatal rats.

Methods: SE was induced by an intraperitoneal injection of kainic acid (KA) in 21‐ and 9‐day‐old (P21 and P9) rats. The expression of Bax, Bcl‐2 and caspase‐3, markers for apoptosis, and cyclooxygenase‐2 (COX‐2), an indicator for activation of inflammatory processes, were studied from 6 h up to 1 week after SE by Western blotting and immunocytochemistry. Neuronal damage was verified by Fluoro‐Jade B staining.

Results: In P21 rats, SE resulted in neuronal damage in the CA1 neurons of the hippocampus. COX‐2 expression was extensively, but transiently, increased and its immunoreactivity pronouncedly enhanced in several hippocampal subregions, amygdala, and piriform cortex by 24 h after SE. The expression of Bax and caspase‐3 remained unchanged, whereas the antiapoptotic factor Bcl‐2 transiently decreased by 24 h. Single caspase‐3 positive neurons appeared in the CA1 region of both control and KA‐treated rats. In P9 rats, no neuronal death was detected, and COX‐2 expression and immunoreactivity remained at the control level.

Discussion: Our results suggest that SE provokes age‐specific effects on COX‐2 expression. This together with the activation of putative inflammatory processes may contribute to neuronal cell death in the hippocampus of postnatal rats, whereas caspase‐dependent apoptosis seems not to be involved in the death process.
GABAA receptor‐mediated activation of L‐type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas
Authors: Kim Do Young , Fenoglio Kristina A. , Simeone Timothy A. , Coons Stephen W. , Wu Jie , Chang Yongchang , Kerrigan John F. , Rho Jong M.
Published: May 2008

Summary

Purpose: The human hypothalamic hamartoma (HH) is a rare, intrinsically epileptogenic lesion associated with gelastic seizures, but the underlying mechanisms remain unclear. Here, we examined the role of GABAA receptors in surgically resected HH tissue.

Methods: HH tissue slices (350 μm) were studied using cellular electrophysiological, calcium imaging, and immunocytochemical techniques.

Results: Two neuronal cell types were seen: small (10–16 μm) spontaneously firing GABAergic neurons and large (20–28 μm) quiescent neurons. In gramicidin‐perforated patch recordings, muscimol (30 μM) induced membrane depolarization in 70% of large (but not small) neurons and a concomitant rise in intracellular calcium. These responses were blocked by bicuculline methiodide (50 μM). Depolarizing neurons also exhibited more positive reversal potentials (Emuscimol) and significantly higher intracellular chloride concentrations compared to those that hyperpolarized. The cation chloride co‐transporters NKCC1 and KCC2 were coexpressed in the majority of large neurons, but fluorometric measurements revealed that 84% of large HH neurons expressed solely or relatively more NKCC1. Bumetanide (20 μM), a NKCC1 antagonist, partially suppressed muscimol‐induced excitation in large neurons. Concordant with robust expression of CaV1.2 and CaV1.3 subunits in HH neurons, the L‐type calcium channel blocker nifedipine (100 μM) prevented muscimol‐induced neuronal excitation.

Conclusions: GABAA receptor‐mediated excitation, due in part to differential expression of NKCC1 and KCC2 and subsequent activation of L‐type calcium channels, may contribute to seizure genesis in HH tissue. Given the ready availability of L‐type calcium channel blockers, our results have clinical ramifications for the treatment of seizures associated with HH lesions.
Do observer and self‐reports of ictal eye closure predict psychogenic nonepileptic seizures?
Authors: Syed Tanvir U. , Arozullah Ahsan M. , Suciu Gabriel P. , Toub Julia , Kim Hyunmi , Dougherty Michelle L. , Wehner Tim , Stojic Andrey , Syed Ishtiaq , Alexopoulos Andreas V.
Published: May 2008

Summary

Purpose: Diagnostic delay in distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures may result in unnecessary therapeutic interventions and higher health care costs. Previous studies demonstrated that video‐recorded eye closure is associated with PNES. The present study prospectively assessed whether observer or self‐report of eye closure could predict PNES, prior to video‐EEG monitoring.

Methods: Adults referred to an epilepsy monitoring unit (EMU) were prospectively enrolled into the study. At baseline, self‐report of eye closure was assessed by questionnaire, and observer report was obtained by interview. Physicians viewed video clips independent of EEG tracings and determined the duration of eye closure during PNES and epileptic seizures. We evaluated whether video‐recorded eye closure identified an episode as PNES using random effects models that accounted for episode clustering by subject. The utility of observer and self‐report of eye closure in predicting a diagnosis of PNES was tested using logistic regression.

Results: Of 132 enrolled subjects, 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%) or epilepsy (n = 84, 75.0%). Fifteen of the 43 PNES subjects (34.9%) had coexisting epilepsy. Self and observer reports of eye closure were neither sensitive nor specific for the diagnosis of PNES. Self‐report of eye closure more accurately predicted actual video‐recorded eye closure than observer report. Video‐recorded eye closure was 92% specific, but only 64% sensitive for PNES identification.

Discussion: Neither observer nor self‐report of eye closure, prior to VEEG monitoring, predicts PNES. Video‐recorded eye closure may not be as sensitive an indicator of PNES as previously reported.
Are MRI‐detected brain abnormalities associated with febrile seizure type?
Authors: Hesdorffer Dale C. , Chan Stephen , Tian Hong , Allen Hauser W. , Dayan Peter , Leary Linda D. , Hinton Veronica J.
Published: May 2008

Summary

Objective: Whether magnetic resonance imaging (MRI) is informative in febrile seizures (FS) is unknown. We undertook a study to determine the frequency of MRI‐detected brain abnormalities and to evaluate their association with FS type and with specific features of complex FS.

Methods: A prospective cohort study, from 1999 to 2004, included children with first FS from one Pediatric Emergency Department. MRI of the brain was performed within 1 week of the seizure. FS type was categorized by experts blind to the prior clinical history and MRI results. MRI examinations were read blind to the child's clinical history and FS type, and interviewers were blind to MRI results.

Results: In 159 children with a first FS, imaging abnormalities occurred in 12.6% (N = 20). Eight of the 54 with complex FS had imaging abnormalities compared to 12 of the 105 with simple FS (n.s.). Compared to children with simple FS, children with both focal and prolonged FS (N = 14) were more likely to have imaging abnormality (OR = 4.3, 95% CI = 1.2–15.0), even after adjustment for abnormal neurological examination. Imaging abnormalities included those known to be associated with seizures (e.g., focal cortical dysplasia) and those not typically associated with seizures (e.g., subcortical focal hyperintensities ≥ 5 mm).

Discussion: Our data suggest that brain abnormalities may lower seizure threshold in febrile children, predisposing to the development of FS. Clinical management was unaffected and therefore these data do not alter the recommendation that MRI is unnecessary in children with FS, without some other neurological indication.
Cytogenesis in the dentate gyrus after neonatal hyperthermia‐induced seizures: What becomes of surviving cells?
Authors: Lemmens Evi M.P. , Schijns Olaf E.M.G. , Beuls Emile A.M. , Hoogland Govert
Published: May 2008

Summary

Purpose:Febrile seizures (FS) are early‐life seizures thought to play a role in epileptogenesis. By labeling cells that were dividing immediately following experimental FS, we previously demonstrated that significantly more of these newborn cells in the dentate gyrus (DG) survived 8 weeks later, relative to animals that did not experience FS. The purpose of the present study was to determine the long‐term fate of these newborn cells.

Methods:On postnatal day (PN) 10, hyperthermia‐induced seizures (HT, ±42°C core temperature) were evoked in Sprague‐Dawley rats and littermates were used as normothermia controls (NT, ±35°C core temperature). From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we evaluated the number of BrdU‐labeled cells in the DG that colocalized with the neuronal marker NeuN, glial marker glial fibrillary acidic protein (GFAP), neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67) or microglia marker tomato lectin (TL).

Results:In all rats, almost all BrdU‐labeled cells in the DG, that showed double‐labeling, colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT controls and HT rats that did not experience seizures (“HT‐no seizures”), ∼23% of BrdU‐labeled cells colocalized with EAAT3, which was significantly different from 14% in HT rats that did experience seizures (HT + FS).

Discussion:Early‐life seizures decrease the population of newborn cells that survive and mature into EAAT3‐positive neurons and do not affect the GABAergic cell population. This may affect hippocampal physiology in young adulthood.
Effects of early‐life LiCl‐Pilocarpine‐induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein
Authors: De Oliveira Diogo Losch , Fischer Alice , Jorge Renan Sanna , Da Silva Mariane Castro , Leite Marina , Gonçalves Carlos Alberto , Quillfeldt Jorge Alberto , Souza Diogo Onofre , E Souza Tadeu Mello , Wofchuk Susana
Published: May 2008

Summary

Purpose: This study investigated putative correlations among behavioral changes and: (1) neuronal loss, (2) hippocampal mossy fiber sprouting, and (3) reactive astrogliosis in adult rats submitted to early‐life LiCl‐pilocarpine‐induced status epilepticus (SE).

Methods: Rats (P15) received LiCl (3 mEq/kg, i.p.) 12–18 h prior pilocarpine (60 mg/kg; s.c.). At adulthood, animals were submitted to behavioral tasks and after the completion of tasks biochemical and histological analysis were performed.

Results: In SE group, it was observed an increased number of degenerating neurons in the CA1 subfield and in the hilus of animals 24 h after SE. At adulthood, SE group presented an aversive memory deficit in an inhibitory avoidance task and the animals that presented lower latency to the step down showed a higher score for mossy fiber sprouting. In the light‐dark exploration task, SE rats returned less and spent less time in the light compartment and present an increased number of risk assessment behavior (RA). There was a negative correlation between the time spent in the light compartment and the score for mossy fiber sprouting and a positive correlation between score for mossy fiber sprouting and number of RA. LiCl‐pilocarpine‐treated animals showed higher levels of S100B immunocontent in the CSF as well as a positive correlation between the score for sprouting and the GFAP immunocontent in the CA1 subfield, suggesting an astrocytic response to neuronal injury.

Conclusions: We showed that LiCl‐pilocarpine‐induced SE during development produced long‐lasting behavioral abnormalities, which might be associated with mossy fiber sprouting and elevated CSF S100B levels at adulthood.
Evaluation of epileptogenic networks in children with tuberous sclerosis complex using EEG‐fMRI
Authors: Jacobs Julia , Rohr Axel , Moeller Friederike , Boor Rainer , Kobayashi Eliane , LeVan Meng Pierre , Stephani Ulrich , Gotman Jean , Siniatchkin Michael
Published: May 2008

Summary

Purpose: Ninety percent of patients with tuberous sclerosis complex (TSC) have epilepsy. Identification of epileptogenic areas can be difficult and studies are needed to characterize the epileptogenic network in more detail.

Methods: Five children with TSC and focal epilepsy were studied using simultaneous EEG and functional MRI recordings. Tubers were marked by a neuroradiologist on the anatomical MRI. Spike‐associated BOLD (blood oxygenation level‐dependent) responses were superimposed with lesions.

Results: Thirteen different types of interictal epileptiform discharges (IED) were analyzed with 12 showing a BOLD response, all involving more than one tuber.

Five studies had tubers with activations exclusively within the lesion, three studies had lesional activations extending to perilesional areas, and two studies had activations involving exclusively perilesional areas of at least one tuber. Deactivations exclusively within a tuber were found in six studies, lesional deactivations extending to perilesional areas were found in four studies, and tubers with exclusively perilesional deactivations were found in five studies.

A BOLD response was found in at least one tuber in the lobe of IED generation and presumed seizure onset (according to telemetry) in all patients. In four patients, the same tubers were involved following different IED localizations. The observed changes were always multifocal, sometimes involving tubers distant from the IED field.

Discussion: These findings suggest extended epileptogenic networks in patients with TSC, which exceed networks described in PET and SPECT studies. It was possible to identify specific interictally active tubers. EEG‐fMRI provides a noninvasive method to select tubers and areas at their borders for further presurgical investigations.
Quality of Pharmacotherapy and Outcomes for Older Veterans Discharged from the Emergency Department
Authors: Hastings S. Nicole , Schmader Kenneth E. , Sloane Richard J. , Weinberger Morris , Pieper Carl F. , Goldberg Kenneth C. , Oddone Eugene Z.
Published: May 2008

OBJECTIVES: To determine whether suboptimal pharmacotherapy increases the risk of adverse outcomes in older adults discharged from the emergency department (ED).

DESIGN: Retrospective, cohort study.

SETTING: Academically affiliated Veterans Affairs Medical Center.

PARTICIPANTS: Nine hundred forty‐two veterans aged 65 and older discharged from the ED.

MEASUREMENTS: The primary independent variable, suboptimal pharmacotherapy, was based on drugs‐to‐avoid criteria, drug–drug interactions, drug–disease interactions, or failure to satisfy explicit quality indicators (QIs). An adverse outcome was defined as one or more repeat ED visits or hospitalizations or death within 90 days of ED discharge.

RESULTS: Four hundred twenty‐one patients were prescribed a new medication at ED discharge. Of these, 134 (31.8%) had suboptimal pharmacotherapy; 49 (11.6%) were prescribed a drug to avoid, 53 (12.6%) received a drug that introduced a new drug–drug interaction, 24 (5.7%) were given a drug that introduced a drug–disease interaction, and 74 (17.6%) did not have a QI satisfied. Overall, 320 patients (34.0%) experienced an adverse outcome within 90 days. Multivariable analyses suggested a trend toward greater risk of adverse outcomes in patients with suboptimal pharmacotherapy (hazard ratio=1.32, 95% confidence interval=0.95, 1.84).

CONCLUSION: A substantial number of older male veterans discharged from the ED may be at risk for adverse events due to suboptimal prescribing and inadequate medication monitoring. Efforts to improve the quality of pharmacotherapy in this vulnerable population are warranted.
Use of Urinary Collection Devices in Skilled Nursing Facilities in Five States
Authors: Rogers Mary A. M. , Mody Lona , Kaufman Samuel R. , Fries Brant E. , McMahon Laurence F. , Saint Sanjay
Published: May 2008

OBJECTIVES: To assess use of urinary collection devices (external, intermittent, and indwelling catheters; pads or briefs) and examine predictors of indwelling catheters in skilled nursing facilities (SNFs).

DESIGN: Retrospective cohort study.

SETTING: SNFs in California, Florida, Michigan, New York, and Texas.

PARTICIPANTS: All patients admitted to SNFs in 2003 who remained there for 1 year (N=57,302).

MEASUREMENTS: Characteristics of patients who used different collection strategies (indwelling, intermittent, and external catheterization; pads or briefs) and predictors of indwelling urinary catheterization from the Nursing Home Minimum Data Set using multinomial logistic regression.

RESULTS: The prevalence of indwelling catheterization was 12.6% at admission and 4.5% at the annual assessment (P<.001). Intermittent and external catheterization were infrequently used (<1% at admission and annual assessment). Paraplegia, quadriplegia, multiple sclerosis, and comatose state were strongly associated with indwelling catheterization. Male residents were more likely to use an indwelling catheter at every assessment, as were obese patients; individuals with diabetes mellitus, renal failure, skin conditions, deep vein thrombosis, aphasia, or end‐stage disease; and those who were taking more medications.

CONCLUSION: Coinciding with federal regulations, urinary catheterization was lower than has been reported previously and declined over time. Further reduction should be targeted at the evaluation of skin problems, appropriateness of multiple medications, and alternative measures in patients with diabetes mellitus, obesity, deep vein thrombosis, and communication problems.
Understanding the Mechanisms of Senile Osteoporosis: New Facts for a Major Geriatric Syndrome
Authors: Duque Gustavo , Troen Bruce R.
Published: May 2008

Knowledge of the underlying mechanisms of osteoporosis in older adults has significantly advanced in recent years. There is an acute loss of bone mineral density in the peri‐menopausal period, followed by a more gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow. This study reviews new evidence on the pathophysiology of senile osteoporosis, with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in elderly people that focus on the pathophysiology and potential reversal of the adipogenic shift in bone.
Effect of viral nucleic acid testing on contamination frequency of manufacturing plasma pools
Authors: Nübling C. Micha , Unkelbach Uwe , Chudy Michael , Seitz Rainer
Published: May 2008

BACKGROUND:In Europe, all plasma pools used for manufacturing of plasma derivatives must be tested negative for hepatitis C virus (HCV) RNA by nucleic acid amplification techniques (NAT) with a defined minimal sensitivity. For a subset of pools, quantitative B19V DNA NAT is also mandatory. NAT for further viral targets was introduced by most of the manufacturers on a voluntary basis. The contamination frequency of plasma pools with HCV RNA, human immunodeficiency virus (HIV)‐1 RNA, and hepatitis B virus (HBV) DNA was investigated with representative pools before and after introduction of NAT.

STUDY DESIGN AND METHODS:A total of 873 pools from 1996 and 331 pools from 2006 were analyzed for the detection of HCV RNA, HIV RNA, and HBV DNA with an automated multiplex NAT system. The pools were obtained from different manufacturers and the source material was of European and US origin.

RESULTS:HCV RNA, HIV‐1 RNA, and HBV DNA were detectable in plasma pools from 1996 with the following frequencies: 17.8 percent (HCV RNA), 0.8 percent (HIV‐1 RNA), and 0.5 percent (HBV DNA). Viral genome concentrations were up to 3 × 104 IU HCV RNA per mL and 7 × 103 IU HIV RNA per mL, whereas HBV DNA was below the quantitation limit of the quantitative NAT assay. Among the pools from 2006, one pool (0.3%) was found HCV RNA–positive at low titer (<10 IU/mL), whereas no HIV RNA or HBV DNA was detectable in any pool.

CONCLUSION:The results imply that the introduction of NAT systems for the detection of viral genomes has largely reduced the contamination frequency and viral loads of manufacturing plasma pools and thereby improved the safety margin for human medicinal products manufactured from human plasma. Even with NAT, however, low‐titer contamination may occur, which will be coped with by virus inactivation steps included into the manufacturing of plasma derivatives.
Long‐term survival rate of pediatric patients after blood transfusion
Authors: Gauvin France , Champagne Martin A. , Robillard Pierre , Le Cruguel Jean‐Pierre , Lapointe Hélène , Hume Heather
Published: May 2008

BACKGROUND: Studies in adults report posttransfusion survival rate (PTSR) at 1 to 10 years of 41 to 67 percent. There are no published studies specifically addressing PTSR in pediatric patients. The objectives of this study were to evaluate PTSR and risk factors associated with death in children receiving transfusions.

STUDY DESIGN AND METHODS: A database of all patients receiving their first transfusion between 1990 and 1992 at Sainte‐Justine Hospital (SJH) was used. Patients' demographic data, primary diagnosis, surgical procedures, and information on all labile components transfused were collected. Death was confirmed by the SJH database, RAMQ (universal health care provider for Québec residents), and the Quebec Commission for Access to Information (death certificate).

RESULTS: The study population consisted of 1100 children. Median age was 16 months (range, 0‐204 months). The most frequent primary diagnoses were cardiac disease (22%), prematurity (21.5%), malignant disease (11%), and hematologic disease (9.5%). Patients received a median of three transfusions (range, 1‐126). PTSR was 86.9 percent at 1 year and 82.3 percent at 10 years. For nonsurvivors, median survival time was 22 days. Multivariate analysis showed that significant risk factors for death are age of less than 1 month, a diagnosis of malignant disease, more than 20 transfusions, and administration of more than one type of blood component.

CONCLUSION: PTSR in children receiving their first transfusion between 1990 and 1992 was considerably higher than the PTSR reported in adults. Death occurred early after the first transfusion; survival rate remained relatively stable thereafter.
Quantitative expression of Toll‐like receptor‐2, ‐4, and ‐9 in dendritic cells generated from blasts of patients with acute myeloid leukemia
Authors: Schmitt Anita , Li Li , Giannopoulos Krzysztof , Greiner Jochen , Reinhardt Peter , Wiesneth Markus , Schmitt Michael
Published: May 2008

BACKGROUND: Dendritic cells (DCs) generated from leukemic blasts constitute a promising tool in immunotherapy for acute myeloid leukemia patients (AML‐DCs), because AML‐DCs express human leukocyte antigens and costimulatory molecules such as CD40, CD80, and CD86 at a higher level than leukemic blasts. Potentiation of AML‐DC vaccine might become feasible by the addition of adjuvants such as lipopolysaccharides (LPS) or CPG‐rich oligodeoxyribonucleotides binding to Toll‐like receptors (TLR) and inducing a stronger Type 1 T‐cell response.

STUDY DESIGN AND METHODS: mRNA and protein expression of TLR‐2, ‐4, and ‐9 were analyzed with quantitative real‐time polymerase chain reaction, Western blot, and flow cytometry for mature monocyte‐derived DCs generated from 14 AML patients versus 14 healthy volunteers (HV‐DCs), and the response of the AML‐ and HV‐DCs to different microbial TLR ligands was determined by enzyme‐linked immunosorbent assay for the proinflammatory cytokines tumor necrosis factor (TNF)‐α, inducible protein (Ip)‐10, and interleukin (IL)‐6.

RESULTS: AML‐DCs and HV‐DCs strongly expressed TLR‐2 and TLR‐4, while TLR‐9 was expressed at a lower level in both groups. There was no significant difference in TLR expression between the two groups of AML‐DCs and HV‐DCs. In accordance with the TLR expression levels, DCs generated from both AML patients and HVs responded to the known microbial ligands peptidoglycan (PGN) and lipoteichoic acid for TLR‐2 and LPS as ligand for TLR‐4, by producing TNF‐α and IL‐6. A response to the ODNs 2006 and 2216 binding to TLR‐9 was only detected in AML‐DCs.

CONCLUSION: Microbial ligands like ODNs and LPS constitute promising adjuvants for enhancing (AML‐) DC vaccines.
Cesarean section due to fetal distress increases the number of stem cells in umbilical cord blood
Authors: Manegold Gwendolin , Meyer‐Monard Sandrine , Tichelli Andre , Pauli Doris , Holzgreve Wolfgang , Troeger Carolyn
Published: May 2008

BACKGROUND: Umbilical cord blood (UCB) can be used as hematopoietic stem cell source for transplantation. The success of a transplantation is highly correlated with the number of total nucleated cells (TNCs) and CD34+ cells in the UCB. Certain obstetric factors increase the yield of stem cells in the UCB. It is necessary to evaluate optimal conditions in labor to decrease the rate of sample rejection due to low cell count. No data exist regarding the difference between primary and secondary Cesarean sections in terms of efficacy of stem cell harvesting.

STUDY DESIGN AND METHODS: Seventy‐nine consecutive UCB units from women who had a Cesarean section between 1997 and 2003 were included. The number of TNCs, CD34+ cells, colony‐forming units (CFUs), white blood cells (WBCs), nucleated red blood cells (NRBCs), and the total collection volume were compared between cases with primary and secondary Cesarean section.

RESULTS: UCB obtained after a Cesarean section due to fetal distress has significantly higher numbers of TNCs, CD34+ cells, NRBCs, and WBCs compared to elective Cesarean section. Of the cases with secondary Cesarean section due to fetal distress, 67 percent resulted in UCB units with sufficient TNC numbers (≥80 × 107 TNCs) compared to 42 percent of the cases with primary Cesarean section.

CONCLUSION: Fetal distress increases the number of hematopoietic stem cells mobilized into UCB. Particular effort should be made to collect UCB from newborns who experienced fetal distress.
Declining hepatitis C rates in first‐time blood donors: insight from surveillance and case‐control risk factor studies
Authors: O'Brien Sheila F. , Fan Wenli , Xi Guoliang , Yi Qi‐Long , Goldman Mindy , Fearon Margaret A. , Infante‐Rivard Claire , Chiavetta Jo Anne , Willems Bernard , Pi David , Fast Margaret , Delage Gilles
Published: May 2008

BACKGROUND: Hepatitis C virus (HCV) rates have decreased steadily in first‐time donors in Canada since testing was implemented but reasons are unclear. A description of factors that may have played a role in this decline is reported.

STUDY DESIGN AND METHODS: Descriptive analysis of first‐time blood donors by HCV positivity status and year (1993‐2006), sex, and age was carried out. HCV‐positive first‐time donors and matched controls participated in a confidential scripted telephone interview about risk factors in 1993 through 1994 and in 2005 through 2006, and risk factors independently predicting HCV positivity were determined with multiple logistic regression.

RESULTS: HCV‐positive donations occurred most frequently in donors born between 1945 and 1964 and decreased in this birth cohort over time (p < 0.01). At present, most first‐time donors (74%) are born after 1964. History of intravenous drug use, sex with an intravenous drug user, blood transfusion, and tattoo independently predicted (p < 0.01) HCV positivity in both periods (1993‐1994 and 2005‐2006).

CONCLUSION: Most HCV‐positive donors were born between 1945 and 1964, and the decline in HCV rates is associated primarily with this birth cohort. The key risk factors predicting HCV positivity did not change over the 13 years of the study. With approximately two‐thirds of HCV‐positive Canadians in the general population having been tested for HCV, potential donors may be aware of their HCV status and be likely to self‐defer. This, and an increasing proportion of first‐time donors born after 1964, may contribute to declining HCV rates in first‐time donors.
Prediction of red cell and blood volumes distribution by various nomograms: do current nomograms overestimate?
Authors: Holme Stein , Elfath M. Dean , Heaton Andrew , Whitley Pamela , McNeil Deanna
Published: May 2008

BACKGROUND: Currently used formulas for estimation of a person's red cell volume (RCV) by weight and height are decades old and were based on the use of 51Cr isotopes and on a sample population, which may not be reflective of today's population. In this study, the accuracy and precision of the use of 99mTc RCV measurements in volunteers more typical of today's population were evaluated.

STUDY DESIGN AND METHODS: The subjects were volunteers who met the requirements for a standard blood donation.

RESULTS: The mean ± standard deviation (SD) 99mTc RCV for 127 males (mean weight, 83.2 kg; height, 180 cm) was 2062 ± 339 mL, and for 101 females (mean weight, 69.5 kg; height, 166 cm) it was 1320 ± 201 mL. These results were highly correlated with RCV results with the standard extrapolation 51Cr method with stored red blood cells (RBCs) and highly consistent (within ±10%) by repeated measurements with the same 22 donors over a 3.5‐year period. The RCV results correlated with estimates from the current formulas, but were on average 11 to 14 percent lower.

CONCLUSION: The studies demonstrated that 99mTc is a reproducible and precise method for determination of a person's RCV and that current formulas may significantly overestimate the RCV of today's population. This is likely the result of a shift in population characteristics over the past four decades as reflected by an increased mean body mass index (from 25 to 28 kg/m2), which has not resulted in a proportionally increased RCV.
Does an alloimmune response to strong immunogenic red blood cell antigens enhance a response to weaker antigens?
Authors: Schonewille Henk , Brand Anneke
Published: May 2008

BACKGROUND: It has been suggested that an immune response against the high immunogenic D antigen also augments the immune response to less immunogenic red blood cell (RBC) antigens. Based on the high antibody frequency, E and K antigens can also be regarded as strong immunogens. The question is whether the immunization against E and K antigens also enhances the formation of other antibody specificities. This question is in particular relevant for patients who are currently transfused with RH‐ and/or K‐matched RBCs.

STUDY DESIGN AND METHODS: A retrospective multicenter study analyzed FY, JK, and MNS antibodies alone and in combination with anti‐E and/or anti‐K. Analysis was performed for primary and subsequent antibody responses.

RESULTS: In the cohort analyzed, 5016 patients possessed 5981 antibodies. Antibodies directed to multiple blood group systems were present in 606 of the 779 (78%) patients with multiple antibodies. In 88 of 1270 (6.9%) patients, FY, JK, and/or MNS antibodies appeared simultaneous with anti‐E and/or anti‐K during a primary antibody response after transfusion. Patients formed antibodies to antigens in the FY, JK, and MNS systems equally often as first antibodies followed by anti‐E or anti‐K than as second antibodies after anti‐E or anti‐K were already present. Patients with anti‐E and/or anti‐K or with antibodies to antigens in the FY, JK, and/or MNS systems equally often formed additional antibodies during a second antibody response.

CONCLUSION: An immune response against allogeneic RBC antigens defines good responders who readily form antibodies against other antigens. No support was found that the response against strong RBC antigens also enhances the formation against weaker antigens.
Acute hemolysis of transfused A2 red cells by an auto‐HI antibody
Authors: Darabi Kamran , Makar Robert S.
Published: May 2008

BACKGROUND: Anti‐HI is a common cold autoantibody that complicates serologic testing for underlying alloantibodies and has only rarely been associated with hemolysis. An unusual case of an acute hemolytic transfusion reaction (AHTR) due to an anti‐HI autoantibody in a subgroup A1 patient transfused with A2 red blood cells (RBCs) is reported.

CASE REPORT: A 56‐year‐old man presented to the hospital with anemia and gastrointestinal tract bleeding. His medical history was significant for congestive heart failure, obesity, and pulmonary hypertension. On admission, he was noted to have a hemoglobin level of 7.7 g per dL and therefore transfusion of RBCs was ordered. The patient was group A, D– with a reactive antibody screen due to a cold autoantibody with HI specificity. Further serologic investigation did not detect any alloantibodies. The patient was issued an electronically cross‐matched group A, D– unit of RBCs. Several hours after the transfusion, he was found to be producing “Coca‐cola”‐colored urine with gross hemoglobinemia visible in a posttransfusion specimen, indicating an AHTR. A transfusion reaction investigation excluded mistransfusion or a missed alloantibody and instead revealed that the patient's anti‐HI had a high thermal amplitude and that the implicated unit of RBCs was from the A2 subgroup. The patient subsequently tolerated transfusion of a unit of group A1 RBCs through a blood warmer without any signs or symptoms of hemolysis.

CONCLUSION: This case illustrates that anti‐HI autoantibodies rarely may behave like alloantibodies and cause AHTRs. Subsequent RBC transfusion with an appropriate ABO group or subgroup through a blood warmer is well tolerated.
Government Program Usage and Political Voice*
Authors: Mettler Suzanne , Stonecash Jeffrey M.
Published: May 2008

Objectives. Despite the scope of U.S. social spending, we know little about cumulative program usage among individuals or how it may influence their political attitudes or behavior. This article examines program usage among citizens and probes the association of usage with program assessment and the likelihood of voting.

Methods. We examine these issues using the 2005 Maxwell Poll, which uniquely asked respondents about both usage of 18 social programs as well as attitudes about such programs and rates of political involvement.

Results. The data indicate that direct experience of social programs is fairly common and widespread across the population, but beneficiaries of programs differ in their assessments compared to nonbeneficiaries. Most significant, after controlling for various demographic factors, we find that the greater the number of universal programs citizens have used, the greater the likelihood that they vote; conversely, the greater the number of means‐tested programs they have used, the lower their likelihood of voting.

Conclusion. Experiences of social programs may influence voter turnout and may help explain why young and less advantaged citizens vote less than older citizens. Trends in social provision may be fostering inequality of political voice, particularly among younger generations.
Faith and Politics: The Influence of Religious Beliefs on Political Participation*
Authors: Driskell Robyn , Embry Elizabeth , Lyon Larry
Published: May 2008

Objective. The relationship between religion and political participation has not been rigorously investigated, typically employing only basic measures of church attendance or denomination. In this study, we utilize precise measures of various religious behaviors, traditions, and beliefs to examine their influence on political participation.

Methods. Using data from the Baylor Religion Survey 2005, we demonstrate that merely including measures of church attendance or denomination camouflages much of religion's influence on political participation.

Results. We find that religious beliefs are significantly related to national political participation. For religious activities, identifying with a religious tradition reduces participation, but participation in church activities increases political participation.

Conclusion. Different types of religious beliefs influence political participation differently. Although some macro religious beliefs significantly increase macro political behavior, believers in an involved God are less likely to participate politically. Individualistic, micro beliefs have no affect on national politics. Thus, the scope of the religious belief fits with the scope of the political activity, in that more macro concerns translate to national political participation.
Democracy Out of Anarchy: The Prospects for Post‐Civil‐War Democracy*
Authors: Gurses Mehmet , Mason T. David
Published: May 2008

Objective. This study explores the effects of civil war outcome on post‐civil‐war democratization. We employ an expected utility model to argue that the attributes of the civil war that lead to balanced power relations between the warring parties lead to higher levels of postconflict democracy.

Methods. We estimate a series of OLS regression models with change in the level of democracy (from the prewar level to five and ten years after the conflict ended) as the dependent variable.

Results. Civil wars that end in negotiated settlements are more likely to experience higher levels of democratization than civil wars that end in military victory by either side. Identity‐based conflicts lead to lower levels of democratization while previous democratic experience seems to decrease post‐civil‐war democratization. We find no support for the argument that high war costs and U.N. peace‐keeping forces produce higher levels of democracy.

Conclusions. Civil war may lead to more inclusive polities if it serves to even the balance of power between contending groups in the nation. Power balance is more likely to bring about more democratic polities, especially where power sharing is formalized in a negotiated settlement.
Measuring Legislator Ideology*
Authors: Griffin John D.
Published: May 2008

Objective. Previous models of roll‐call voting have either ignored the role of legislator ideology or have employed questionable measures of it. A defensible measure of legislator ideology is needed.

Methods. This study surveys former members of Congress (MCs) to obtain a new measure of legislator preferences. The measure has several attractive properties, appears to be valid, and is unique compared to a preference measure others have used.

Results. Validating the measure in a model of roll‐call voting reveals that the importance of legislators' ideologies is similar to that of their party affiliations.

Conclusions. A useful measure of legislators' ideologies can be generated using a postretirement instrument.