Biomedical subjects

Reinhold Schmidt

Publications and source records attributed to Reinhold Schmidt.

At least 37 records · Page 2Linked to original sources

PubMed2005

Ischemic and endotoxin pre-conditioning reduce lung reperfusion injury-induced surfactant alterations.

BACKGROUND: Pulmonary ischemia/reperfusion injury represents a common clinical phenomenon after lung transplantation, pulmonary embolism, and cardiac surgery with extracorporeal circulation. We investigated the influence of ischemic and endotoxin pre-conditioning on gas exchange and surfactant properties in a canine model of ischemia/reperfusion injury. METHODS: Twenty-six foxhounds underwent 3 hours of warm ischemia of the left lung, followed by 8 hours of reperfusion. Ischemic pre-conditioning was performed for either 5 minutes (IPC-5) or by 2 10-minute ischemic periods (IPC-10), before ischemia. For endotoxin pre-conditioning, dogs were pre-treated by a daily intravenous application of increasing amounts of endotoxin for 6 days. No pre-conditioning was performed in the controls. Bronchoalveolar lavage was performed before ischemia/reperfusion injury (baseline) and after the 8-hour reperfusion period in the non-injured right and in the reperfused left lung. Bronchoalveolar lavage fluids were analyzed for the phospholipid-protein ratio, the content of large surfactant aggregates, the phospholipid and neutral lipid profile, the surfactant protein (SP) content, and for biophysical activity. RESULTS: Severe surfactant alterations were observed in the ischemia/reperfusion-injured left lung, with increased protein concentrations and depressed concentrations of large surface aggregates, SP-B, dipalmitoylated phosphatidylcholine, and phosphatidylglycerol. Endotoxin pre-conditioning and IPC-5 were both capable of greatly preventing the ischemia/reperfusion injury-related deterioration of surfactant properties. IPC-10 exerted no effects. Endotoxin pre-conditioning and IPC-5, but not IPC-10, also prevented loss of gas exchange. CONCLUSIONS: Ischemic and endotoxin pre-conditioning may protect against impairment of gas exchange in ischemia/reperfusion injury by restoring physiological surfactant properties.

Animals↗

PubMed2005

Host defence lectins in preterm neonates.

AIM: Deficiency in collectins is discussed as a risk factor for pulmonary and systemic infections in children and adults. The objective of this study was to determine serum concentrations of surfactant protein D (SP-D) and mannose-binding lectin (MBL) in preterm and term infants at birth. METHODS: 47 preterm infants below 32 wk gestational age (GA) and 19 healthy, term newborn infants at birth have been included in the study, and SP-D as well as MBL concentrations have been determined in umbilical cord blood samples using sandwich ELISA technique. In addition, SP-D concentrations were assessed in tracheal aspirates (TA) of 24 mechanically ventilated preterms and in infants without pulmonary complications before elective surgery. RESULTS: MBL serum concentrations were significantly lower in preterms <32 wk GA (756.7 ng/ml; 14.6-11 184 ng/ml) compared to term newborns (3168.9 ng/ml; 282.3-7679.5 ng/ml; p=0.005; median and range, respectively). Serum SP-D concentrations were significantly decreased in preterms between 28 and 32 wk GA (1.4 ng/ml; 0-4.6 ng/ml; n=26) compared to term infants (2.2 ng/ml; 1.2-3.3 ng/ml; p=0.05) and were found to positively correlate with history of antenatal corticosteroids and chorioamnionitis. SP-D concentrations in TA were increased in preterm infants between 28 and 32 wk GA with respiratory distress syndrome (RDS) (25.0 ng/ml; 0.9-44.7 ng/ml; n=12) compared to control subjects (6.6 ng/ml; 0.5-30.4 ng/ml; n=12) in contrast to extremely immature infants <28 wk GA suffering from RDS (4.4 ng/ml; 0.8-78.4 ng/ml; n=12). CONCLUSION: In preterm infants, significant changes occur in collectin umbilical cord blood concentrations and pulmonary SP-D levels. Functional aspects of these findings need to be addressed further.

Enzyme-Linked Immunosorbent Assay↗

PubMed2004

Angiotensinogen promoter B-haplotype associated with cerebral small vessel disease enhances basal transcriptional activity.

BACKGROUND AND PURPOSE: Previously, we described the presence of 5 haplotypes (A to E) at the angiotensinogen (AGT) promoter and reported a significant association between the B-haplotype (nucleotide substitutions -6:G-->A and -20:A-->C compared with the wild-type A-haplotype) and magnetic resonance imaging correlates of cerebral small vessel disease (cSVD). The association was independent of hypertension, suggesting a brain-specific effect of this haplotype. In the current study, we investigated transcriptional activities of the 5 promoter haplotypes in astrocytes, the main source of cerebral AGT, and in hepatocytes, the main source of systemic AGT, as well as determined the evolutionary relatedness of the promoter haplotypes. METHODS: Transcriptional activity depending on the haplotypes and the -6:A and -20:C substitutions was measured in transiently transfected A172 and HepG2 cells. We genotyped 5 new single nucleotide polymorphisms (SNPs) at the AGT gene and measured linkage disequilibrium (LD) among SNPs and the promoter haplotypes. An evolution-based haplotype tree was constructed. RESULTS: The B-haplotype increased transcriptional activity in both cell types. Its effect was stronger in astrocytes than in hepatocytes (2.4+/-0.09-fold, P<0.001 versus 1.6+/-0.06-fold, P=0.014). Importantly, in astrocytes the combination of the -6:A and the -20:C was mandatory for increased activity, whereas in hepatocytes the -20:C on its own was sufficient. Strong LD between the 5 new SNPs and the promoter haplotypes allowed the reconstruction of 9 haplotypes over the AGT gene. Cladistic analyses suggest that the B-haplotype represents an ancient promoter variant. CONCLUSIONS: Combination of the -6:A and -20:C substitutions in the B-haplotype may promote the development of cSVD by enhancing cerebral angiotensinogen expression.

Angiotensinogen↗

PubMed2004

The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study.

Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account.

Aged↗

PubMed2004

Pulmonary surfactant, lung function, and endobronchial inflammation in cystic fibrosis.

Cystic fibrosis (CF) lung disease is primarily a disease of the small airways. We hypothesized that even in patients with normal lung function, a reduced surfactant function would be present and favor small airway obstruction. Bronchoalveolar lavages from 76 patients with CF (5-31 years, median 11) with well-conserved lung function (FEV1 94% predicted, range 78-121) and from 10 healthy control subjects were investigated. The deviation of the biophysical surfactant performance from normal, assessed in a bubble surfactometer, was small; however, the ability of the surfactant to maintain the patency of a narrow airway (% open) was significantly reduced. Surfactant protein (SP)-C level was increased, SP-B and SP-D were unchanged, whereas SP-A was decreased. Among the patients with CF, neutrophilic inflammation was modestly related to a poorer surfactant activity, but not to lung function. SP-D was reduced in proportion to the degree of inflammation and in the presence of bacteria. These findings in a large cohort of patients with CF with normal lung function show that the endobronchial airway inflammation is linked to early perturbations of the biophysical properties and immunologic components of pulmonary surfactant and opens fields for novel therapeutic interventions.

Adolescent↗

PubMed2004

Changes in pulmonary surfactant function and composition in bleomycin-induced pneumonitis and fibrosis.

Bleomycin is a widely accepted cancer drug but may induce life-threatening interstitial lung disease in a subset of patients. We evaluated the effect of bleomycin administration on pulmonary surfactant function and composition in rabbit lungs. In order to obtain a uniform response to bleomycin, aerosol technology was employed for bronchoalveolar delivery of 1.8 U/kg b.w. bleomycin. On days 4, 8, 16, 24, 32, and 64 after challenge, bronchoalveolar lavages were performed. Sham-aerosolized rabbits served as controls. In the early acute respiratory distress syndrome (ARDS)-like post-bleomycin period (4-16 days), marked loss of surface activity of the large surfactant aggregate (LA) fraction of surfactant was noted. In parallel, reduced percentages of LA, but only minor changes in surfactant apoproteins (SP)-A, SP-B, and SP-C, were encountered. Analysis of the surfactant lipid profile showed impressively enhanced cholesterol and significantly decreased phosphatidylglycerol (PG) levels. The relative content of dipalmitoyl-PC (DPPC) was slightly increased, and a several-fold increase within the 1-O-alkyl-2-acyl subclass of PC was observed. During the prolonged fibroproliferative period, a highly significant downregulation of SP-B and SP-C levels was observed. This was paralleled by an upregulation of the total extracellular phospholipid pool, with a far-reaching normalization of the (phospho)-lipid profile. The biophysical surfactant function never fully normalized within the 64-day observation period. In conclusion, bleomycin caused marked abnormalities of pulmonary surfactant, with the profile of changes being different between the early ARDS and the late fibrotic phase.

Administration, Inhalation↗

PubMed2004

Increase in alveolar antioxidant levels in hyperoxic and anoxic ventilated rabbit lungs during ischemia.

Increases in free radicals are believed to play a central role in the development of pulmonary ischemia/reperfusion (I-R) injury, leading to microvascular leakage and deterioration of pulmonary surfactant. Continued ventilation during ischemia offers significant protection against I-R injury, but the impact of alveolar oxygen supply both on lung injury and on radical generation is still unclear. We investigated the influence of hyperoxic (95% O2) and anoxic (0% O2) ventilation during ischemia on alveolar antioxidant status and surfactant properties in isolated rabbit lungs. Normoxic and hyperoxic ventilated, buffer-perfused lungs (n = 5 or 6) and native lungs (n = 6) served as controls. As compared with controls, biophysical and biochemical surfactant properties were not altered in anoxic as well as hyperoxic ventilated ischemic (2, 3, and 4 h) lungs. Assessment of several antioxidants (reduced glutathione (GSH), alpha-tocopherol (vitamin E), retinol (vitamin A), ascorbic acid (vitamin C), uric acid, and plasmalogens (1-O-alkenyl-2-acyl-phospholipids)) in bronchoalveolar lavage fluid (BALF) revealed a significant increase in antioxidant compounds under anoxic and hyperoxic ventilation, with maximum levels occuring after 3 h of ischemia. For example, GSH increased to 5.1 +/- 0.8 microM (mean +/- SE, p <.001) after 3 h of anoxic ventilated ischemia and to 2.7 +/- 0.2 microM (p <.01) after hyperoxic ventilated ischemia compared with native controls (1.3 +/- 0.2 microM), but did not significantly change under anoxic and hyperoxic ventilation alone. In parallel, under ischemic conditions, oxidized glutathione (GSSG) increased during hyperoxic (3 h: 0.81 +/- 0.04 microM, p <.001), but remained unchanged during anoxic (3 h: 0.31 +/- 0.04 microM) ventilation compared with native controls (0.22 +/- 0.02 microM), whereas F2-isoprostanes were elevated under both hyperoxic (3 h: 63 +/- 15 pM, p <.01) and anoxic (3 h: 50 +/- 9 pM, p <.01) ventilation compared with native controls (16 +/- 4 pM). We conclude that oxidative stress is increased in the lung alveolar lining layer during ischemia, during both anoxic and hyperoxic ventilation. This is paralleled by an increase rather than a decrease in alveolar antioxidant levels, suggested to reflect an adaptive response to oxidative stress during ischemia.

Animals↗

PubMed2004

Effect of pulmonary surfactant on TNF-alpha-activated endothelial cells and neutrophil adhesion in vitro.

Pulmonary surfactant given to infants and adults with respiratory failure is metabolized and recycled to a large extent. A small proportion also enters the circulation in cases of increased permeability of the alveolar-capillary membrane. We therefore investigated whether exogenous surfactants such as a natural bovine (natSF) or a synthetic (synSF) preparation had an impact on inflammatory conditions involving the adhesion of neutrophils to endothelial cells. Human umbilical cord vein endothelial cells (HUVEC) were plated on coverslips until confluence, activated by tumor necrosis factor-alpha and incubated with or without surfactant in the media. Human neutrophils passed the HUVEC layer in a flow chamber and interactions were visualized using a video microscope. To test if surfactant affected the expression of cell adhesion molecules, RT-PCR analyses were performed for E-selectin, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Using concentrations between 50 and 300 microg/ml of surfactant in the pre-incubation media the number of adherent neutrophils increased by 10-20% at the higher concentration of the natSF (*P < 0.05) whereas the synSF had no effect. Increased neutrophil adhesion was associated with a significant up-regulation of mRNA levels for E-selectin and VCAM-1; mRNA levels for ICAM-1, however, were not affected by the presence of surfactant. These observations indicate that natSF but not synSF might have pro-inflammatory effects when higher amounts of the exogenous dose reach the circulation. This might be explained by different fatty acid profiles, e.g. the presence of arachidonic acid in the natSF or higher concentrations of surfactant-associated protein-C in the synSF.

Cell Adhesion↗

PubMed2004

Surfactant abnormalities after single lung transplantation in dogs: impact of bronchoscopic surfactant administration.

OBJECTIVE: Disturbances of the alveolar surfactant system have been implicated in the pathogenesis of reperfusion injury. The aim of this study was to evaluate the influence of exogenous surfactant administration on surfactant properties in a model of single lung transplantation. METHODS: We performed heterologous, left lung transplantation (+4 degrees C ischemia; 24 hours, Euro-Collins solution) in 6 foxhounds (untreated) and in 6 animals that received calf lung surfactant extract (Alveofact) prior to explantation (only donor lung; 50 mg/kg body weight) and immediately after onset of reperfusion (both lungs, 200 mg/kg body weight). Separate but synchronized ventilation of each lung was performed, in a volume-controlled, pressure-limited mode, with animals in prone position. Bronchoalveolar lavage fluids were collected in pretransplantation lungs (control), after 24 hours of ischemia prior to transplantation (0 hours) and 6 and 12 hours after reperfusion in both the grafts and the recipient native lungs. RESULTS: Ischemic storage per se did not provoke any changes of the surfactant system; however, severe alterations occurred within 6 hours of reperfusion, resulting in a severe loss of surface activity, including a decrease in the percentage of the large surfactant aggregate fraction, reduction of the surfactant apoproteins SP-B and SP-C, the dipalmitoyl molecular species of phosphatidylcholine and phosphatidylglycerol within the large surfactant aggregate fraction. These abnormalities were restricted to the graft, with virtually normal surfactant function and composition being found in the recipient native lung. Surfactant administration fully normalized the biochemical and largely improved the biophysical surfactant properties, alongside maintenance of lung gas exchange properties. CONCLUSIONS: Severe surfactant abnormalities occur exclusively in the graft when performing separate, synchronized ventilation of each lung to attenuate ventilator-induced lung injury. Bronchoscopic surfactant administration provides protection against these abnormalities and may be a therapeutic strategy in lung transplantation.

Animals↗

PubMed2004

Bronchoscopic surfactant administration preserves gas exchange and pulmonary compliance after single lung transplantation in dogs.

BACKGROUND: Surfactant abnormalities have been implicated in reperfusion injury and respiratory failure in lung transplantation. METHODS: We investigated the efficacy of bronchoscopic administration of a bovine natural lung surfactant extract (Alveofact) to improve gas exchange and lung mechanics after heterologous left lung transplantation in foxhounds (+4 degrees C ischemia for 24 hours, conservation with Euro-Collins solution). Animals received either no surfactant therapy (untreated controls, n = 6) or 50 mg/kg body weight (prior to explantation, only graft) and 200 mg/kg body weight Alveofact (immediately after reperfusion, both lungs, n = 6). After lung transplantation, separate but synchronized ventilation of each lung was performed in a volume-controlled, pressure-limited mode for 12 hours, with the animals prone. Small catheters were inserted into the pulmonary veins of both the graft and the recipient's native lung for separate blood gas analysis. In the control group, marked protein leakage, influx of neutrophils into the alveolar space, and pulmonary edema formation (extravascular lung water; wet/dry ratio) were encountered in the transplanted lung but only to a very minor extent in the recipient's native lung. RESULTS: Lung compliance values and arterial oxygenation progressively deteriorated in the transplanted but not in the native lungs. Pulmonary hemodynamics did not change significantly. Surfactant administration did not significantly influence the development of reperfusion edema, protein leakage, and neutrophil influx into the grafts. However, surfactant restored the surface activity and the gas exchange (PaO2/FIO2 of 201.2 +/- 20.2 mm Hg vs 119.8 +/- 21.7 mm Hg in controls; P <.05) in the transplanted lungs, and compliance was markedly improved in the surfactant-treated animals (18.8 +/- 1.8 mL/mbar vs 11.5 +/- 1.6 mL/mbar in the controls; P <.05). CONCLUSION: Bronchoscopic surfactant administration does not prevent leukocyte influx or vascular leakage but does protect against respiratory failure and improves lung mechanics in single lung transplantation in dogs.

Animals↗

PubMed2004

Qualitative MRI: evidence of usual aging in the brain.

The understanding of aging in our society with steadily increasing life expectancy is an important challenge in medical science since socioeconomic pressure increases in parallel. Magnetic resonance imaging is a most useful tool to explore age related changes in the central nervous system especially in the brain. This article will focus on current knowledge and importance of such changes. Special attention will paid to white matter hyperintensities in terms of occurrence and progression and cerebral microbleeds in terms of their association to various diseases and their possible influence on thrombolytic therapy. Furthermore the meaning of darkening of the basal ganglia will be discussed and, in more general terms, the occurrence of virchow robin spaces and changes in cerebral metabolites assessable by proton magnetic resonance spectroscopy.

Aging↗

PubMed2004

Stroke prevention and atrial fibrillation: reasons leading to an inappropriate management. Main results of the SAFE II study.

AIMS: The aim of the Stroke and Atrial Fibrillation Ensemble (SAFE) II study was to identify the reasons underlying the under-utilization of oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We investigated from all available sources the reasons why patients hospitalized for a stroke, who had a previously known NVAF, were not receiving OAC beforehand. We interviewed general practitioners (GPs) and cardiologists with a structured questionnaire, to identify the reasons for their therapeutic choice. RESULTS: Of 370 patients, 257 were theoretically eligible for OAC according to guidelines and the presence of contra-indications, but only 82 (22.2%) of them had actually received OAC before. We found that factors independently associated with the prescription of OAC were being followed-up by a cardiologist and having a younger GP. The leading reason evoked by GPs or cardiologists to explain why patients were not treated with OAC was the presence of a 'potential contra-indication', which was often inappropriate, followed by 'there was no indication', 'low compliance' and 'fear of bleeding'. CONCLUSIONS: An important reason for not prescribing OAC was the lack of knowledge about trials and guidelines. Medical education about OAC in NVAF should therefore be improved.

Aged↗

PubMed2004

Treatment strategies in Alzheimer's disease with a focus on early pharmacological interventions.

Complex interactive effects of genetic predisposition, neurochemical changes and disease comorbidity have been elucidated in the genesis of dementia syndromes. Alzheimer's disease is the most prevalent type of dementia in developed Western countries. In Alzheimer's disease, pharmacological treatment aims at symptomatic relief, disease modification or disease prevention. Cholinesterase inhibitors are established for the treatment of mild-to-moderate Alzheimer's disease. In Europe and the US, memantine is approved for the treatment of moderate-to-severe Alzheimer's disease. To date, there are no drugs with a disease modifying action that have proven efficacy in randomised, double-blind, placebo-controlled clinical trials. In patients not fulfilling the diagnostic criteria for early Alzheimer's disease, e.g. mild cognitive impairment, the efficacy of several drugs, mainly cholinesterase inhibitors, is currently tested in prospective studies by determining the conversion rate to Alzheimer's disease. However, prevention and disease-modifying strategies raise ethical questions because interventions are focused on non-diseased elderly at risk, which means that emphasis should be not only on efficacy but also on long-term safety. No disease-modifying strategy can presently be offered to patients; however, given the pace of recent research there is optimism that slowing progression of Alzheimer's disease will soon be possible.

Aged↗

PubMed2004

Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study.

Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations.

Aged↗

PubMed2003

Synthetic and natural surfactant differentially modulate inflammation after meconium aspiration.

OBJECTIVE: Meconium aspiration syndrome remains a relevant cause of neonatal respiratory failure and is associated with severe pulmonary changes including surfactant inactivation and pronounced inflammatory changes. The present study investigated the effect of two different surfactant preparations-recombinant surfactant protein C surfactant (rSP-C Surf) and natural bovine surfactant-on pulmonary gas exchange and inflammatory response. DESIGN AND SUBJECTS: Twenty-three newborn piglets were intubated, mechanically ventilated, received 5 ml/kg 20% sterile meconium for induction of lung injury, and were randomized thereafter for controls ( n=7), rSP-C Surf ( n=8), or natural surfactant ( n=8). Surfactants were given as an intratracheal bolus (75 mg/kg) and animals were further ventilated. MEASUREMENTS AND RESULTS: Lung function variables, arterial blood gas samples and lung tissues were obtained. Histological evaluation was performed in right lung tissue using an established score. Cytokine mRNA expression (left lung tissue) was quantified using TaqMan real-time PCR (DeltaDeltaCT method, normalized to controls). In addition to significant improvement in gas exchange and lung function, histological evaluation showed significantly lower sum scores in the rSP-C Surf group than in controls). Cytokine mRNA expression of IL-1beta in whole lung tissue was significantly lower after administration of rSP-C Surf than in natural surfactant and controls whereas IL-10 mRNA expression was significantly induced in both surfactant groups. CONCLUSIONS: Surfactant administration improved both gas exchange and pulmonary inflammatory cytokine transcription. Mechanisms underlying the differential inflammatory response in both surfactant preparations need to be further addressed.

Animals↗

PubMed2003

Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study.

BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.

Brain↗

PubMed2003

Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study.

More than half of all elderly people have some degree of cerebral white matter lesions. However, the rate of progression of these lesions is uncertain. We aimed to assess the progression of lesions in community-dwelling volunteers aged 50-75 years without neuropsychiatric disease. We used MRI to grade and measure the total volume of white matter lesions in 296 volunteers at baseline, 3 years, and 6 years. 58 participants with no lesions and 123 with punctate abnormalities at baseline had a low tendency for lesion progression, whereas 14 participants with early confluent and nine with confluent lesions underwent median increases of 2.7 cm(3) (IQR 0.5-5.9) and 9.3 cm(3) (7.1-21.0), respectively, in lesion volume at 6 years. Lesion grade at baseline was the only significant predictor of lesion progression (p<0.0001). Punctate white matter lesions are not progressive and are thus benign, whereas early confluent and confluent white matter abnormalities are progressive, and thus malignant.

Aged↗

PubMed2003

Lower levels of N-acetylaspartate in multiple sclerosis patients with the apolipoprotein E epsilon4 allele.

BACKGROUND: In multiple sclerosis (MS), the epsilon4 allele of apolipoprotein E (APOE epsilon4) has been associated with more rapid clinical worsening and more severe tissue damage on magnetic resonance imaging. OBJECTIVE: To use proton magnetic resonance spectroscopy ((1)H-MRS) to further explore the biochemical changes in the brains of patients with MS associated with APOE epsilon4. DESIGN: A 2-year clinical and (1)H-MRS follow-up cohort study. SETTING: The MS outpatient clinic, Department of Neurology, and Magnetic Resonance Center of Karl-Franzens University. PATIENTS: We performed (1)H-MRS of the central portion of both hemispheres and APOE genotyping in 72 patients (52 women and 20 men; mean +/- SD age, 34.8 +/- 8.8 years) with clinically definite relapsing-remitting MS. Repeated studies were performed in 44 patients after a mean +/- SD interval of 34 +/- 9 months. MAIN OUTCOME MEASURE: Levels of N-acetylaspartate as measured by (1)H-MRS. RESULTS: Patients with MS and an epsilon4 allele (n = 19) had a significantly lower mean +/- SD N-acetylaspartate-creatine ratio than those without an epsilon4 allele (n = 53) (1.73 +/- 0.26 vs 1.89 +/- 0.24; P =.04) despite the absence of significant differences in age at onset, disease duration, Expanded Disability Status Scale score, and number of previous relapses between subgroups. During follow-up, the drop in the N-acetylaspartate-creatine ratio of epsilon4 carriers was also significantly larger (-0.31 vs -0.10; P =.01). This was paralleled by a higher number of relapses (mean +/- SD, 4.1 +/- 2.7 vs 1.7 +/- 1.6; P =.02) and a faster although nonsignificant progression of disability (mean +/- SD (Delta)Expanded Disability Status Scale score, 0.9 +/- 1.8 vs 0.3 +/- 1.1; P =.19). CONCLUSIONS: The APOE epsilon4 allele has a negative effect on the course of MS, and increasing axonal damage may be an important mechanism.

Adult↗