Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 234
Filter
1.
Ned Tijdschr Geneeskd ; 1652021 11 22.
Article in Dutch | MEDLINE | ID: mdl-35138747

ABSTRACT

Recent trials of two classes of glucose-lowering drugs (SGLT2 inhibitors and GLP1RAs) have shown consistent cardiovascular and renal benefits that appear independent of glycaemic control. These results have prompted the Dutch College of General Practitioners (NHG) together with the Dutch Society of Internal Medicine (NIV) to update the treatment algorithm in patients with type 2 diabetes mellitus (T2D) at very high CVD risk. The use of SGLT2 inhibitors or GLP1RAs is now recommended in 3 groups of people with T2D. 1. patients with established CVD; 2. Patients with chronic kidney disease and a moderately to high CVD risk according to KDIGO; 3. patients with heart failure with reduced ejection fraction (HFrEF). Treatment algorithms differ for drug-naïve and drug-treated patients with T2D. In both drug-naïve and drug-treated patients the use of a SGLT2 inhibitor respectively as monotherapy or add-on is recommended as first step. If HbA1c is above the individual target, metformin will be added in drug-naive patients whereas GLP1-RAs could be considered in drug-treated patients. GLP1-RAs should also be considered when SGLT2-inhibitors are contraindicated.


Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Algorithms , Diabetes Mellitus, Type 2/drug therapy , Heart Failure/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume
2.
Eur J Prev Cardiol ; 26(2_suppl): 47-54, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31766914

ABSTRACT

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called 'pre-diabetes', comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.


Subject(s)
Prediabetic State/diagnosis , Prediabetic State/therapy , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/etiology , Disease Progression , Glucose Intolerance , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Humans , Life Style , Risk
3.
Osteoarthritis Cartilage ; 27(3): 378-391, 2019 03.
Article in English | MEDLINE | ID: mdl-30529739

ABSTRACT

OBJECTIVE: Conduct a systematic review of systematic reviews and randomised controlled trials (RCTs) from the past year evaluating rehabilitation for people with osteoarthritis, and provide narrative synthesis of findings focused on core recommended treatments for osteoarthritis (exercise, education, biomechanical interventions, weight loss). DESIGN: A comprehensive search strategy was used to search PubMed, EMBASE and Cochrane databases (16th May 2017 to 22nd March 2018). Search terms included 'osteoarthritis', 'rehabilitation', 'systematic review', and 'randomised controlled trial'. Inclusion criteria were: (1) RCT, or systematic review of randomised clinical trials (RCTs); (2) human participants with osteoarthritis (any joint); (3) evaluation of rehabilitation intervention; and (4) at least one patient-reported measure. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (systematic reviews) and PEDro rating scale (RCTs). Narrative synthesis mapped findings to core recommendations from existing osteoarthritis clinical guidelines. RESULTS: From 1994 records, 13 systematic reviews and 36 RCTs were included. 73% of these evaluated knee osteoarthritis (36 studies). The remaining studies evaluated hand osteoarthritis (6 studies), hip, hip/knee and general osteoarthritis (each 2 studies), and neck osteoarthritis (1 study). Exercise was the most common intervention evaluated (31%). Updated recommendations for exercise prescription and preliminary guidance for psychological interventions are provided. CONCLUSION: Level 1 and 2 osteoarthritis rehabilitation literature continues to be dominated by knee osteoarthritis studies. Consistent with current clinical guidelines, exercise should be a core treatment for osteoarthritis, but future studies should ensure that exercise programs follow published dose guidelines. There is a clear need for research on rehabilitation for hip, hand, foot/ankle, shoulder and spine osteoarthritis.


Subject(s)
Osteoarthritis/rehabilitation , Humans , Treatment Outcome
4.
Psychol Med ; 48(7): 1092-1101, 2018 05.
Article in English | MEDLINE | ID: mdl-29429419

ABSTRACT

BACKGROUND: Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse. METHOD: Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions. RESULTS: Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls. CONCLUSIONS: The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.


Subject(s)
Brain Mapping , Child Abuse/psychology , Fear/psychology , Gyrus Cinguli/physiopathology , Prefrontal Cortex/physiopathology , Adolescent , Anger , Case-Control Studies , Child , Facial Expression , Female , Happiness , Humans , Magnetic Resonance Imaging , Male , United Kingdom , Young Adult
5.
Osteoarthritis Cartilage ; 26(7): 912-919, 2018 07.
Article in English | MEDLINE | ID: mdl-29427724

ABSTRACT

OBJECTIVE: To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later. METHOD: Individuals from a prospective cohort of individuals aged 50-79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA. RESULTS: Relative to knees without lateral meniscal pathology at baseline, those with grades 3-4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 [95% CI: 1.1-2.7) and (1.7 [1.2-2.5]), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1-2 (0.6 [0.4-0.9]) and 3-4 (0.7 [0.5-1.0]) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later. CONCLUSION: Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ.


Subject(s)
Cartilage Diseases/pathology , Disease Progression , Magnetic Resonance Imaging/methods , Menisci, Tibial/pathology , Osteoarthritis, Knee/pathology , Patellofemoral Joint/pathology , Age Factors , Aged , Cartilage Diseases/diagnostic imaging , Cartilage Diseases/epidemiology , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Cohort Studies , Evaluation Studies as Topic , Female , Humans , Logistic Models , Male , Menisci, Tibial/diagnostic imaging , Middle Aged , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/epidemiology , Patellofemoral Joint/diagnostic imaging , Prevalence , Prognosis , Prospective Studies , Risk Assessment , Severity of Illness Index , Sex Factors , United States
6.
Psychol Med ; 48(6): 1034-1046, 2018 04.
Article in English | MEDLINE | ID: mdl-29122037

ABSTRACT

BACKGROUND: Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. METHODS: Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. RESULTS: For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. CONCLUSIONS: Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.


Subject(s)
Cerebral Cortex/pathology , Child Abuse/psychology , Gray Matter/pathology , Adolescent , Brain Mapping , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Organ Size , Young Adult
7.
Ethn Dis ; 27(Suppl 1): 303-312, 2017.
Article in English | MEDLINE | ID: mdl-29158655

ABSTRACT

Objective: Bicycling is an affordable way to increase access to employment, schooling, and services and an effective measure against obesity. Bikeshare programs can make bicycling accessible to diverse populations, but little evidence exists on their adoption in low-resource neighborhoods. Our study examined factors associated with bikeshare use in a metropolitan area in the southern United States. Methods: We performed a retrospective cross-sectional analysis of a database of clients (N=815) who rented a bicycle from Zyp Bikeshare in Birmingham, Alabama between October 2015 and November 2016. Individual-level variables included bike use frequency, average speed, total miles traveled, total minutes ridden, bike type (traditional vs electricity-assisted pedelec), membership type, sex, and age. Area-level data aggregated to Census tracts, proxies for neighborhoods, were obtained from the 2010 US Census after geocoding clients' billing addresses. Using exploratory factor analysis, a neighborhood socioeconomic disadvantage index (SDI) was constructed. Bikeshare station presence in a tract was included as a covariate. Multivariate linear regression models, adjusted for clustering on Census tracts, were estimated to determine predictors of bikeshare use. Results: In a multivariate regression model of individual and neighborhood characteristics adjusted for clustering, each decile increase in the SDI was associated with a 9% increase in bikeshare use (P<.001). Bikeshare use was also positively associated with speed (.1, P<.001), total miles (.008, P<.001), and pedelec use (1.02, P<.01). Conclusion: Higher neighborhood socioeconomic disadvantage is associated with higher bikeshare use. Bikeshare is a viable transportation option in low-resource neighborhoods and may be an effective tool to improve the connectivity, livability, and health of urban communities.


Subject(s)
Bicycling/statistics & numerical data , Residence Characteristics/statistics & numerical data , Urban Population , Adult , Alabama , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Humans , Male , Retrospective Studies , Socioeconomic Factors
8.
Phys Rev Lett ; 117(9): 093201, 2016 Aug 26.
Article in English | MEDLINE | ID: mdl-27610852

ABSTRACT

We propose a novel scheme for resolving the contribution of inner- and outer-valence electrons in extreme-ultraviolet (XUV)-initiated high-harmonic generation in neon. By probing the atom with a low-energy (below the 2s ionization threshold) ultrashort XUV pulse, the 2p electron is steered away from the core, while the 2s electron is enabled to describe recollision trajectories. By selectively suppressing the 2p recollision trajectories, we can resolve the contribution of the 2s electron to the high-harmonic spectrum. We apply the classical trajectory model to account for the contribution of the 2s electron, which allows for an intuitive understanding of the process.

9.
J Musculoskelet Neuronal Interact ; 13(4): 496-500, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24292620

ABSTRACT

We investigated the immediate effects of a varus knee brace on knee symptoms and knee-joint biomechanics in an individual with predominant lateral tibiofemoral joint osteoarthritis (TFJOA) and valgus malalignment after anterior cruciate ligament (ACL) reconstruction. A varus unloader brace was prescribed to a 48-year-old male with predominant lateral radiographic and symptomatic TFJOA and valgus malalignment eight-years following ACL reconstruction. During a step-down task, the participant rated knee pain, task-difficulty, knee-stability and knee-confidence on four separate visual analogue scales. Quantitative gait analysis was conducted during self-selected walking trials under three test conditions in a randomized order: (i) no brace; (ii) brace without frontal plane adjustment (no varus re-alignment); and (ii) brace with frontal plane adjustment (varus re-alignment). Post-processing of gait data involved calculation of knee kinematics and net joint moments for the reconstructed limb. The participant reported improved pain (3%), task difficulty (41%), stability (46%) and confidence (49%) when performing the step-down task with the brace. The varus brace resulted in immediate reductions in knee abduction angle (24%) and internal rotation angle (56%), and increased knee adduction moment (18%). These findings provide preliminary evidence for potentially beneficial effects of bracing on knee-symptoms and biomechanics in individuals with lateral TFJOA after reconstruction.


Subject(s)
Braces , Gait/physiology , Knee Joint/surgery , Osteoarthritis/rehabilitation , Anterior Cruciate Ligament Reconstruction , Biomechanical Phenomena/physiology , Humans , Male , Middle Aged , Osteoarthritis/physiopathology , Osteoarthritis/surgery , Treatment Outcome
10.
Biologicals ; 40(6): 473-81, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22901944

ABSTRACT

During the manufacture of human plasma derivatives, a series of complementary measures are undertaken to prevent transmission of blood-borne viruses. Virus filtration using 15 nm (Planova15N) filters has successfully been implemented in manufacturing processes for various plasma derivatives primarily because virus filtration is a technique, mild for proteins, that can effectively remove even small non-lipid-enveloped viruses, such as HAV and parvovirus B19. However, the use of 15 nm filters has limitations with regard to protein capacity of the filters and the process flow, resulting in an expensive manufacturing step. Therefore, studies were performed to test whether the use of 20 nm (Planova20N) filters, having different characteristics compared to 15 nm filters, can be an alternative for the use of 15 nm filters. It is shown that 20 nm filtration can be an alternative for 15 nm filtration. However, the virus removal capacity of the 20 nm filters depends on the plasma product that is filtered. Therefore, an optimisation study must be performed with regard to process parameters such as pressure, pH and protein concentration for each plasma product. In this study, using optimised conditions, the virus removal capacity of 20 nm filters appears to be comparable or even better when compared to that of 15 nm filters.


Subject(s)
Blood Substitutes , Blood-Borne Pathogens/isolation & purification , Filtration/instrumentation , Viruses/isolation & purification , Complement C1 Inactivator Proteins/analysis , Complement C1 Inhibitor Protein , Immunoglobulin G/analysis , Prothrombin/analysis , Transferrin/analysis
11.
Osteoarthritis Cartilage ; 20(8): 863-8, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22525223

ABSTRACT

OBJECTIVES: This study aimed to (1) compare the volumes of vastus medialis (VM), vastus lateralis (VL), vastus intermedius and rectus femoris and the ratio of VM/VL volumes between asymptomatic controls and patellofemoral joint osteoarthritis (PFJ OA) participants; and (2) assess the relationships between cross-sectional area (CSA) and volumes of the VM and VL in individuals with and without PFJ OA. METHODS: Twenty-two participants with PFJ OA and 11 controls aged ≥ 40 years were recruited from the community and practitioner referrals. Muscle volumes of individual quadriceps components were measured from thigh magnetic resonance (MR) images. The CSA of the VM and lateralis were measured at 10 equally distributed levels (femoral condyles to lesser femoral trochanter). RESULTS: PFJ OA individuals had smaller normalized VM (mean difference 0.90 cm(3) · kg(-1), α = 0.011), VL (1.50 cm(3) · kg(-1), α = 0.012) and rectus femoris (0.71 cm(3) · kg(-1), α = 0.009) volumes than controls. No differences in the VM/VL ratio were observed. The CSA at the third level (controls) and fourth level (PFJ OA) above the femoral condyles best predicted VM volume, whereas the VL volume was best predicted by the CSA at the seventh level (controls) and sixth level (PFJ OA) above the femoral condyles. CONCLUSION: Reduced quadriceps muscle volume was a feature of PFJ OA. Muscle volume could be predicted from CSA measurements at specific levels in PFJ OA patients and controls.


Subject(s)
Osteoarthritis, Knee/physiopathology , Patellofemoral Joint/pathology , Quadriceps Muscle/pathology , Aged , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged
12.
Phys Rev Lett ; 108(6): 063006, 2012 Feb 10.
Article in English | MEDLINE | ID: mdl-22401067

ABSTRACT

We investigate the influence of the autoionizing 3s3p(6)nℓ resonances on the fifth harmonic generated by 200-240 nm laser fields interacting with Ar. To determine the influence of a multielectron response we develop the capability within time-dependent R-matrix theory to determine the harmonic spectra generated. The fifth harmonic is affected by interference between the response of a 3s electron and the response of a 3p electron, as demonstrated by the asymmetric profiles in the harmonic yields as functions of wavelength.

13.
Phys Rev Lett ; 105(1): 013001, 2010 Jul 02.
Article in English | MEDLINE | ID: mdl-20867437

ABSTRACT

We have observed the simultaneous inner-shell absorption of two extreme-ultraviolet photons by a Xe atom in an experiment performed at the short-wavelength free electron laser facility FLASH. Photoelectron spectroscopy permitted us to unambiguously identify a feature resulting from the ionization of a single electron of the 4d subshell of Xe by two photons each of energy (93±1) eV. The feature's intensity has a quadratic dependence on the pulse energy. The results are discussed and interpreted within the framework of recent results of ion spectroscopy experiments of Xe obtained at ultrahigh irradiance in the extreme-ultraviolet regime.

14.
Science ; 328(5986): 1645-6, 2010 Jun 25.
Article in English | MEDLINE | ID: mdl-20576879
15.
Phys Rev Lett ; 102(19): 193001, 2009 May 15.
Article in English | MEDLINE | ID: mdl-19518949

ABSTRACT

We use the time-dependent R-matrix approach to investigate an ultrashort pump-probe scheme to observe collective electron dynamics in C+. The ionization probability of a coherent superposition of the 2s2p;{2} 2D and 2S states shows rapid modulation due to collective dynamics of the two equivalent 2p electrons, with the modulation frequency linked to the dielectronic repulsion. The best insight into this collective dynamics is achieved by a transformation from LS symmetry to the uncoupled basis. Such dynamics may be important in high-harmonic generation using open-shell atoms and ions.

16.
Phys Rev Lett ; 101(25): 253001, 2008 Dec 19.
Article in English | MEDLINE | ID: mdl-19113702

ABSTRACT

An attosecond pump-probe scheme that combines the use of a free-electron laser pulse with an ultrashort pulse is applied in order to explore the ultrafast excitation dynamics in Ne. We describe the multielectron dynamics using a new nonperturbative time-dependent R-matrix theory. This theory enables the interaction of ultrashort light fields with multielectron atoms and atomic ions to be determined from first principles. By probing the emission of an inner 2s electron from Ne we are also able to study the bound state population dynamics during the free-electron laser pulse.

17.
Vet Ophthalmol ; 10 Suppl 1: 28-37, 2007.
Article in English | MEDLINE | ID: mdl-17973832

ABSTRACT

OBJECTIVE: The presence of myocilin was investigated in a colony of Beagles, a canine model for inherited primary open-angle glaucoma (POAG). The myocilin protein was localized in the normal and glaucomatous canine eyes by immunohistochemistry and immunocytochemistry. METHODS: Paraffin- and plastic-embedded specimens from the anterior uveas of 10 Beagles with inherited glaucoma (3 months to 13 years old) and 6 age-matched normal dogs were sectioned, and were then incubated with primary antibody, rabbit polyclonal antihuman MYOC IgG, overnight at 4 degrees C. Specimens were incubated with secondary antibody with one of the following: biotinylated link followed by peroxidase-labeled streptavidin and then by substrate-chromogen for light microscopy; fluorescent marker Texas red; or 18 nm colloidal gold-labeled goat antirabbit IgG for transmission electron microscopy. RESULTS: With normal, pre- and early glaucomatous canine specimens, cell membranes of smooth muscle cells of the iris and ciliary body stained positively, as well as most resident stromal and vascular endothelial cells. The cytoplasm of cells within the nonpigmented ciliary epithelium of the ciliary body processes stained intensely, being weaker along the pars plana. Trabecular meshwork (TM) cells and surrounding extracellular matrix labeled, as well as the sclera adjacent to the angular aqueous plexus. In specimens with moderate and advanced glaucoma, greater intensity of staining was observed within TM cells and adjacent sclera, and portions of the nonpigmented epithelium of the ciliary processes. Fibrinous material labeled intensely within the posterior chamber. CONCLUSIONS: Myocilin in the normal and glaucomatous canine eye was successfully immunolocalized. These findings with regard to the normal eye are nearly identical to those previously reported in humans, and support the original hypothesis that there is an increase in both accumulation and localization of myocilin in glaucomatous canine eyes. It also supports the possibility that changes in the activity of myocilin within the aqueous humor outflow pathway of individuals with spontaneous glaucoma are associated with the rise of intraocular pressure and subsequent development of this disease, but may not be the primary event in the initial raise in intraocular pressure in POAG in the Beagle.


Subject(s)
Cytoskeletal Proteins/metabolism , Dog Diseases/metabolism , Eye Proteins/metabolism , Glaucoma, Open-Angle/veterinary , Glycoproteins/metabolism , Uvea/metabolism , Animals , Case-Control Studies , Dogs , Glaucoma, Open-Angle/metabolism , Immunohistochemistry/veterinary
18.
Vox Sang ; 90(1): 21-32, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16359352

ABSTRACT

BACKGROUND AND OBJECTIVES: Producers of plasma derivatives continuously improve the viral safety of their products by, for example, introducing additional virus-reducing steps into the manufacturing process. Here we present virus-elimination studies undertaken for a number of steps employed in a new manufacturing process for liquid intravenous immunoglobulin (Nanogam) that comprises two specific virus-reducing steps: a 15-nm filtration step combined with pepsin treatment at pH 4.4 (pH 4.4/15NF); and solvent-detergent (SD) treatment. The manufacturing process also includes precipitation of Cohn fraction III and viral neutralization, which contribute to the total virus-reducing capacity of the manufacturing process. In addition, the mechanism and robustness of the virus-reducing steps were studied. MATERIALS AND METHODS: Selected process steps were studied with spiking experiments using a range of lipid enveloped (LE) and non-lipid-enveloped (NLE) viruses. The LE viruses used were bovine viral diarrhoea virus (BVDV), human immunodeficiency virus (HIV) and pseudorabies virus (PRV); the NLE viruses used were parvovirus B19 (B19), canine parvovirus (CPV) and encephalomyocarditis virus (EMC). After spiking, samples were collected and tested for residual infectivity, and the reduction factors were calculated. For B19, however, removal of B19 DNA was measured, not residual infectivity. To reveal the contribution of viral neutralization, bovine parvovirus (BPV) and hepatitis A virus (HAV) were used. RESULTS: For the pH 4.4/15NF step, complete reduction (> 6 log(10)) was demonstrated for all viruses, including B19, but not for CPV (> 3.4 but < or = 4.2 log(10)). Robustness studies of the pH 4.4/15NF step with CPV showed that pH was the dominant process parameter. SD treatment for 10 min resulted in complete inactivation (> 6 log(10)) of all LE viruses tested. Precipitation of Cohn fraction III resulted in the significant removal (3-4 log(10)) of both LE and NLE viruses. Virus-neutralization assays of final product revealed significant reduction (> or = 3 log(10)) of both BPV and HAV. CONCLUSIONS: The manufacturing process of Nanogam comprises two effective steps for the reduction of LE viruses and one for NLE viruses. In addition, the precipitation of Cohn fraction III and the presence of neutralizing antibodies contribute to the total virus-reducing capacity of Nanogam. The overall virus-reducing capacity was > 15 log(10) for LE viruses. For the NLE viruses B19, CPV and EMC, the overall virus-reducing capacities were > 10, > 7 and > 9 log(10), respectively. Including the contribution of immune neutralization, the overall virus-reducing capacity for B19 and HAV is estimated to be > 10 log(10).


Subject(s)
Consumer Product Safety , Immunoglobulins, Intravenous , Virus Inactivation , Drug-Related Side Effects and Adverse Reactions/prevention & control , Drug-Related Side Effects and Adverse Reactions/virology , Humans , Immunoglobulins, Intravenous/chemistry
19.
J Intellect Disabil Res ; 49(Pt 4): 288-95, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15816816

ABSTRACT

BACKGROUND: Little research has been conducted on the perceived competence of children with mild intellectual disabilities (MID). One of the reasons for the marked absence of research appears to be the lack of reliable and clearly valid measurement instruments for this particular group of children. In the present study, it was examined whether a pictorial scale originally designed to measure perceived competence in typically developing children could successfully be used with children with MID. METHODS: The pictorial scale was administered to a group of 106 children with MID. The construct validity, reliability and stability of the scale were investigated. RESULTS: The results of the exploratory factor analyses and the confirmatory factor analyses supported the conceptual framework proposed. The construct validity was also supported by the pattern of intercorrelations between the subscales. The scale had adequate internal consistency and the stability analyses showed sufficient stability across a 4-month period. CONCLUSIONS: The findings show the psychometric properties of the pictorial scale to justify its use with children with MID.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/ethnology , Mental Competency , Self Concept , Child , Female , Humans , Male , Netherlands , Photic Stimulation , Severity of Illness Index
20.
J Cardiovasc Magn Reson ; 6(2): 569-76, 2004.
Article in English | MEDLINE | ID: mdl-15137342

ABSTRACT

Isolated ventricular non-compaction (IVNC) is an idiopathic form of cardiomyopathy. Recent clinical reports have suggested that this form of cardiomyopathy is more frequently associated with complications of congestive heart failure, thromboembolism and malignant ventricular arrhythmias. Contrast enhanced cardiac magnetic resonance imaging with its excellent spatial resolution, its large field of view and its ability to demonstrate thrombus and myocardial scar is an excellent modality to non-invasively assess patients with this form of cardiomyopathy. This paper presents a case of familial isolated ventricular non-compaction. We describe the echocardiographic, X-ray angiographic and cardiac MRI findings. Cine imaging using a steady-state free precession sequence (BFFE) was performed in axial and short axis planes. Left ventricular (LV) mass was estimated both with and without the incorporation of trabeculations from a contiguous stack of short axis images. Trabecular mass was expressed as a percentage of total left ventricular mass. We compared trabecular mass: total LV mass in 10 patients with dilated cardiomyopathy. The mean percentage trabecular mass: LV mass in dilated cardiomyopathy was 11.3% (range 1.5%-19%), and this differed significantly from the trabecular mass of the noncompaction patient (two-tailed Mann-Whitney test, p = 0.028). Trabecular mass of greater than 20% of total myocardial mass may be a useful index to suggest the diagnosis of IVNC. Gadolinium was administered (0.1 mmol/kg). Qualitative analysis of first pass perfusion suggested reduced trabecular perfusion. Early imaging with an inversion recovery sequence and a fixed long inversion time did not demonstrate LV thrombus. Late imaging with the same sequence (TI = 280-300 msec) did not demonstrate myocardial fibrosis.


Subject(s)
Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Contrast Media , Gadolinium DTPA , Magnetic Resonance Imaging, Cine/methods , Adult , Humans , Male , Ventricular Dysfunction, Left/genetics , Ventricular Dysfunction, Left/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...