bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of depth filtration to remove prion challenge from an immune globulin preparation
Authors: Van Holten R. W. , Autenrieth S. M. 
Published: December 2004

Background and Objectives Plasma‐derived therapeutic proteins have the potential to contain transmissible spongiform encephalopathy (TSE) infectivity. This study evaluated the effectiveness and characterized the mechanism of abnormal prion protein removal during a depth‐filtration step used in the manufacture of an immunoglobulin preparation.Materials and Methods Scrapie brain homogenate was treated with lysolecithin, sonicated and sequentially filtered through 0·45‐, 0·22‐ and 0·1‐µm membrane filters. The scrapie brain homogenate was then added (at a 1 : 51 dilution) to the Supernatant III fraction used in the manufacture of Rho(D) immune globulin (human). The spiked immunoglobulin preparation was then filtered through a depth filter under the same conditions used in full‐scale production. After filtration, the depth filter was washed with hypertonic NaCl solutions to elute the abnormal prion protein (PrPSc) from the filter. A Western blot assay for PrPSc was used to quantify removal from the filtrate and recovery from the filter washes. A second run was performed whereby the PrPSc‐spiked Supernatant III was filtered through a 0·22‐µm membrane filter prior to depth filtration. A third run evaluated depth filtration of PrPSc in Tris‐buffered saline (TBS).Results The depth filter removed greater than four logs of PrPSc from the Supernatant III filtrate. A significant portion of the PrPSc could be recovered from the depth filter by elution with high‐molarity NaCl solutions. Prefiltration (through a 0·22‐µm membrane filter) of the spiked Supernatant III prior to depth filtration removed all detectable PrPSc. Depth filtration removed less than one log of PrPSc from TBS.Conclusions Depth filtration appears to remove PrPSc from the immunoglobulin preparation by mechanical straining rather than by adsorption to the filter matrix. The immunoglobulin preparation caused the PrPSc to aggregate from particles < 0·1 µm in size to particles of > 0·22 µm, probably as a result of the presence of methanol in the preparation. The depth filter failed to remove PrPSc from a purely aqueous environment.
Reduction of the diagnostic window in three cases of human immunodeficiency‐1 subtype E primary infection with fourth‐generation HIV screening assays
Authors: Weber B. , Thorstensson R. , Tanprasert S. , Schmitt U. , Melchior W. 
Published: December 2004

Background and Objectives The influence of genetic variability on the sensitivity of serological diagnosis of human immunodeficiency virus (HIV) infection has, to date, been poorly investigated. The aim of the present study was to assess whether fourth‐generation assays for the combined detection of HIV antigen and antibodies to HIV (anti‐HIV) permit a reduction of the diagnostic window in comparison to third‐generation antibody enzyme immunoassays (EIAs), which so far have shown a poor sensitivity for detection of HIV‐1 non‐subtype B primary infections.Materials and Methods Three patients with primary HIV‐1 subtype E (CRF01‐AE) infection were tested with different third‐ and fourth‐generation assays, stand‐alone HIV antigen (Ag) EIAs and reverse transcription–polymerase chain reaction (RT–PCR). Additionally, virus lysates from HIV‐1 Group M and O and HIV‐2, at concentrations of p24 Ag close to the detection limit of licensed HIV Ag EIAs, were investigated with fourth‐generation EIAs and HIV Ag EIAs.Results In the first blood donor, the most sensitive fourth‐generation assay detected HIV‐1 infection 11 days earlier than five of the eight third‐generation antibody assays. Fourth‐generation EIAs, with a high sensitivity for HIV antigen, detected HIV‐1 subtype E infection simultaneously or 4 days later than HIV‐1 RT–PCR on pooled samples. Low concentrations of virus lysates of different HIV‐1 subtypes A–H and group O, tested positive with fourth‐generation EIAs, with a high sensitivity of the antigen‐detection module.Conclusions Fourth‐generation EIAs, especially those with a high sensitivity for HIV‐1 p24 antigen, reduce the diagnostic window for primary HIV‐1 subtype E infection in comparison with third‐generation antibody‐screening assays. These preliminary data from seroconversions and virus lysates indicate that the genetic diversity of HIV‐1 does not represent a major challenge for the most sensitive EIAs of this new assay generation.
Early postnatal development of central corneal thickness in dogs
Authors: Montiani‐Ferreira Fabiano , Petersen‐Jones Simon , Cassotis Nicholas , Ramsey David T. , Gearhart Patricia , Cardoso Fernando 
Published: December 2004

AbstractObjectiveTo investigate the changes in corneal thickness that occur during maturation of the canine eye over the first months of life.Animals studiedDogs of two different breeds with ages ranging from 14 days to 42 weeks of age.ProceduresThe central corneal thickness was measured by ultrasonic pachymetry every week for the first month after eyelid opening (around 14 days) and then every month until 42 weeks of age. Segmented regression was applied to capture the two phases observed in the central corneal thickness plotted against age. Breed, eye and gender were also included in the model.ResultsMean central corneal thickness (CCT) values initially decreased following eyelid opening, with the lowest point being reached at around 6 weeks of age. Then CCT gradually increased as the dogs matured. Differences between left and right eye were not significant. Breed and gender effects were significant factors in the statistical model.ConclusionsFollowing eyelid opening there is an initial decrease in corneal thickness until approximately 6 weeks of age, which presumably mirrors maturation of corneal endothelial cell function. After 6 weeks of age the CCT increases with age until approximately 30 weeks of age after which there was only a gradual increase over the remainder of the study period. A similar pattern of changes in corneal thickness in humans has been previously recorded.
The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs
Authors: Ward D. A. , Abney K. , Oliver J. W. 
Published: December 2004

AbstractObjectiveTo assess the effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase (AChE) levels in normal dogs.AnimalsNine adult mixed breed dogs weighing between 18 and 27 kg.ProceduresFifty µL of 0.25% demecarium bromide were applied to one eye of each dog every 8 h for 6 days. Blood was analyzed for AChE levels prior to commencement of eye drops, and at 45 min, 1 h 45 min, 4 h 45 min, 1 day, 3 days, and 7 days following commencement of eye drops using a 5,5′‐dithiobis‐(2‐nitrobenzoic acid) (DTNB) reaction.ResultsAcetylcholinesterase levels declined over the first 24 h following commencement of demecarium administration in most dogs. This decline was highly variable and was statistically significant by 24 h. In some individuals AChE levels were suppressed to levels approaching clinical toxicity. By day 3 AChE levels had risen to levels above baseline in most dogs.ConclusionsTopical ocular application of demecarium causes transient suppression of systemic acetylcholinesterase levels in most dogs. Acetylcholinesterase levels generally do not fall to toxic levels, but may do so in certain individuals. Demecarium bromide eye drops generally do not cause AChE toxicity, but dogs receiving such therapy should be monitored for signs of AChE toxicity, and concomitant use of other AChE inhibitors should be avoided.
Seasonal effects on the aerobic bacterial and fungal conjunctival flora of normal thoroughbred brood mares in Florida
Authors: Andrew Stacy E. , Nguyen An , Jones Galin L. , Brooks Dennis E. 
Published: December 2004

AbstractObjectiveTo evaluate seasonal effects on the presence or absence of fungal and aerobic bacterial flora of the conjunctival fornix of normal Florida Thoroughbred horses.Sample populationBoth eyes of 100 horses.ProcedureHorses with normal anterior segment ophthalmic examinations from three farms in north central Florida were included. Each animal had the ventral conjunctival fornix of each eye swabbed with sterile culturettes. Samples were taken in October, January, April, and July (1999–2000). Aerobic and fungal cultures were plated. Bacterial cultures were reviewed at 24 and 48 h. Fungal cultures were reviewed weekly for 4 weeks. Logistic regression analysis with season as a factor and age of the horse as a covariate was performed. Statistical significance was set atP< 0.01.ResultsHorses ranged from 3 to 24 years of age, with a median age of 9 years. Twenty‐four genera of bacteria and 35 genera of fungi were recovered.Corynebacteriumsp.,Staphylococcussp.,Bacillussp. andMoraxellasp. were the bacteria most frequently isolated. Mold species, dematiaceous mold species,Chrysosporiumsp.,Cladosporiumsp., andAspergillussp. were the most frequently recovered fungi. Season did not have a significant effect on the presence of microorganisms isolated for individual horses adjusted for age. Younger horses had an increased incidence of gram‐negative rods and fungal isolates. The number of bacteria and fungi isolated are not uniform across seasons.ConclusionThere were no significant differences between the number or type of organisms cultured during the sampling seasons in normal Florida horses. A large range of normal bacterial and fungal flora were isolated from these horses. The number of bacteria and fungi isolated are not uniform across seasons. The likelihood of detecting an organism depends on the horses’ age.
Fungal flora of normal eyes of healthy horses from the State of Rio de Janeiro, Brazil
Authors: Rosa Maurílio , Cardozo Liane Maria , Da Silva Pereira Jorge , Brooks Dennis E. , Martins Ana Lucia B. , Florido Penha Sueli Silva , Stussi Jussara Schwind Pedroso 
Published: December 2004

AbstractThe conjunctival fungal flora of 32 adult horses with normal eyes (n = 64) from the State of Rio de Janeiro in Brazil was identified in the fall of 2000 using horses of different breeds, both genders and aged 5–19 years old. The culture samples were taken from the conjunctival sac of both eyes with a sterile cotton swab wetted with saline solution, seeded in Sabouraud's dextrose agar with chloramphenicol, and incubated for 5 days at an average temperature of 25 °C. The number of fungal colonies per eye varied between 0 and 250 colony forming units (CFUs). There were often differences in colony types between eyes of the same animal. Filamentous fungi of genera were isolated and identified in the following proportion of the total genera of fungal colonies isolated: Aspergillus (32.2%), Penicillium (25.8%), Scopulariopsis (15.9%), Trichoderma (11.2%), Cladosporium (5.6%), Mucor (2.1%), Syncephalastrum (2.1%), Eurotium (1.7%), Geotrichum (0.9%), Rhizopus (0.9%), Gliomastix (0.4%), Fusarium (0.4%), Staphylotrichum (0.4%) and Verticillium (0.4%). Yeast genera represented 9% of the total isolates. Over half the horses had at least one normal eye with either Aspergillus, Penicillium, Trichoderma or Scopulariopsis isolated, which is a departure from other studies of the normal horse eye.
Changes in intraocular pressure and pupil size following intramuscular administration of hydromorphone hydrochloride and acepromazine in clinically normal dogs
Authors: Stephan Deborah D. , Vestre W. A. , Stiles Jean , Krohne Sheryl 
Published: December 2004

AbstractObjectiveTo investigate the effects of intramuscularly administered hydromorphone hydrochloride and acepromazine on intraocular pressure (IOP) and pupil size (PS).Animals studiedSeventeen dogs free of clinically relevant ocular abnormalities.ProcedureMeasurements of IOP and PS were obtained and the dogs were injected intramuscularly with hydromorphone (0.04–0.08 mg/kg) and acepromazine (0.04 mg/kg). Measurements of IOP and PS were repeated 10 min and 25 min later.ResultsThough a decreasing trend in IOP values was demonstrated, no significant difference was noted in IOP from the initial examination to examination following intramuscular administration of hydromorphone and acepromazine. Significant miosis was present in 16 of 17 dogs at 10 min and 25 min following administration of hydromorphone and acepromazine.ConclusionHydromorphone (0.04–0.08 mg/kg) and acepromazine (0.04 mg/kg) cause significant miosis in dogs at 10 and 25 min following intramuscular administration.
Young Children's Evaluations of the Ingroup and of Outgroups: A Multi‐National Study
Authors: Bennett Mark , Barrett Martyn , Karakozov Rauf , Kipiani Giorgi , Lyons Evanthia , Pavlenko Valentyna , Riazanova Tatiana 
Published: December 2004

AbstractIn investigating intergroup attitudes, previous research in developmental psychology has frequently confounded ingroup favouritism and outgroup derogation. The present study, using unconfounded measures, examines the possibility that ingroup favouritism and outgroup derogation are distinct phenomena. Six‐year‐old children (n=594) from five, culturally diverse nations were asked to make various evaluations of the national ingroup and of four national outgroups. The data indicate that although there is overwhelming evidence that young children favour the ingroup over other groups, outgroup derogation is limited in extent and appears to reproduce attitudes held by adult members of the particular nations investigated.
Non-Ignorable Missing Covariate Data in Survival Analysis: A Case-Study of an International Breast Cancer Study Group Trial
Authors: Herring Amy H. , Ibrahim Joseph G. , Lipsitz Stuart R. 
Published: December 2004

SummaryNon-ignorable missing data, a serious problem in both clinical trials and observational studies, can lead to biased inferences. Quality-of-life measures have become increasingly popular in clinical trials. However, these measures are often incompletely observed, and investigators may suspect that missing quality-of-life data are likely to be non-ignorable. Although several recent references have addressed missing covariates in survival analysis, they all required the assumption that missingness is at random or that all covariates are discrete. We present a method for estimating the parameters in the Cox proportional hazards model when missing covariates may be non-ignorable and continuous or discrete. Our method is useful in reducing the bias and improving efficiency in the presence of missing data. The methodology clearly specifies assumptions about the missing data mechanism and, through sensitivity analysis, helps investigators to understand the potential effect of missing data on study results.
A Bayesian Method for Estimating the Accuracy of Recalled Depression
Authors: Rutter Carolyn M. , Simon Gregory 
Published: December 2004

Summary
We develop a Bayesian method that allows us to compare weekly depression states recalled for a 3-month period to cross-sectionally assessed measurements of current depression assessed during randomly timed phone interviews. Using these data, we examine the accuracy of recalled depression by linking a spline model for recalled depression and a logistic model for current depression. The logistic model includes the model-based probability of depression based on recall as a covariate and covariates potentially related to the accuracy of recall. The model that we propose allows variability in both measures and can be modified to examine general relationships between longitudinal and cross-sectional measurements.
A Litter-Based Approach to Risk Assessment in Developmental Toxicity Studies via a Power Family of Completely Monotone Functions
Authors: Kuk Anthony Y. C. 
Published: December 2004

SummaryA new class of distributions for exchangeable binary data is proposed that originates from modelling the joint success probabilities of all orders by a power family of completely monotone functions. The distribution proposed allows flexible modelling of the dose–response relationship for both the marginal response probability and the pairwise odds ratio and is especially well suited for a litter-based approach to risk assessment. Specifically, the risk of at least one adverse response within a litter takes on a simple form under the distribution proposed and can be reduced further to a generalized linear model if a complementary log–log-link function is used. Existing distributions such as the beta–binomial or folded logistic functions have a tendency to assign too much probability to zero, leading to an underestimation of the risk that at least one foetus is affected and an overestimation of the safe dose. The distribution proposed does not suffer from this problem. With the aid of symbolic differentiation, the distribution proposed can be fitted easily and quickly via the method of scoring. The usefulness of the class of distributions proposed and its superiority over existing distributions are demonstrated in a series of examples involving developmental toxicology and teratology data.
Wound bed preparation: a systematic approach to wound management
Authors: Schultz Gregory S. , Sibbald R. Gary , Falanga Vincent , Ayello Elizabeth A. , Dowsett Caroline , Harding Keith , Romanelli Marco , Stacey Michael C. , Teot Luc , Vanscheidt Wolfgang 
Published: December 2004

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or “stuck” at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management.This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues;• the current status of wound bed preparation;• an analysis of the acute and chronic wound environments;• how wound healing can take place in these environments;• the role of wound bed preparation in the clinic;• the clinical and cellular components of the wound bed preparation concept;• a detailed analysis of the components of wound bed preparation. (WOUND REP REG 2003;11:1–28)
Effects of vascular endothelial growth factor on wound closure rates in the genetically diabetic mouse model
Authors: Kirchner Loren M. , Meerbaum Sharon O. , Gruber Brian S. , Knoll Andrew K. , Bulgrin Jeffery , Taylor R.A.J. , Schmidt Steven P. 
Published: December 2004

Impaired wound healing is characteristic of diabetic patients. Potential reasons include poor inflammatory response, granulation tissue formation, and abnormal patterns of cytokine release and response. Vascular endothelial growth factor, abnormally regulated during healing in diabetics, is the major factor stimulating angiogenesis during normal wound healing. We tested our hypothesis that topically applied vascular endothelial growth factor would improve wound closure rates in diabetic animals in a full‐thickness wound model in genetically diabetic mice (C57 BL/KsJ db/db). Animals received either 1.0 µg of vascular endothelial growth factor165 or polyethylene glycol alone topically to wounds daily between days 0 and 4 postwounding. Wound area was measured at days 0, 5, 10, 15, and 21. Data were analyzed using probit analysis and expressed as length‐of‐time (LT) to 50, 90, and 95% wound closure. Among untreated animals, nondiabetics had an LT50 of 8.5 days (fiducial limits 8.3–8.7), while diabetics had an LT50 of 15.8 days (15.6–16.1). Vascular endothelial growth factor‐treated animals had LT50 values of 7.8 (7.6–8.1) and 11.8 days (11.6–12.0) for nondiabetics and diabetics, respectively, representing a 25% improvement in time to 50% closure in treated diabetics. We conclude that topically applied vascular endothelial growth factor improves time to wound closure in the genetically diabetic mouse model. (WOUND REP REG 2003;11:127–131)
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Uremia‐Related Metabolic Cardiac Risk Factors in Chronic Kidney Disease
Authors: Madore François 
Published: December 2004

ABSTRACTGrowing evidence has been gathered over the last 15 years regarding the role of nontraditional or uremia‐related risk factors in the pathogenesis of atherosclerosis in subjects with renal failure. Among those factors, dyslipidemia, inflammation, hyperhomocysteinemia, and oxidant stress have been extensively studied. However, the clinical significance of many of these factors remains controversial in light of reported studies. In this article, the existing evidence regarding the role of uremia‐related risk factors in the pathogenesis of atherosclerosis is reviewed, with special emphasis on prevalence, cardiac risk, and management in patients with chronic kidney disease (CKD). Consensus treatment recommendations are provided for risk factors for which there is evidence to support preventive or therapeutic interventions.
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Applying Multiple Interventions in Chronic Kidney Disease
Authors: Barrett Brendan J. 
Published: December 2004

ABSTRACTThe medical, social, and financial burdens posed by end‐stage renal disease (ESRD) are many and growing rapidly. People generally reach ESRD as a result of chronic progressive kidney disease. Advancing kidney disease is associated with several treatable complications, which if poorly managed reduce the length and quality of life. In addition, there are strong links between chronic kidney disease (CKD) and cardiovascular disease (CVD). Many people with less advanced CKD will die or suffer complications of CVD before reaching ESRD. Efficacious interventions, such as lowering blood pressure and treating dyslipidemia, can substantially reduce the progression of both kidney and cardiovascular disease. Careful management of these complex and interrelated diseases and risk factors requires detailed longitudinal and focused care which does not seem to be optimally delivered by health service practitioners organized in traditional ways. A disease management approach offers promise in this setting, but requires further study of clinical and economic impact.