Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

Structural muscle damage and muscle strength after incremental number of isometric and forced lengthening contractions

Summary Exercise-induced muscle damage is characterized by histological changes, like Z-line streaming, inflammatory response and decreased muscle function reflected in a prolonged decline in maximal isometric muscle strength after eccentric work. It is assumed that force decrement is mainly related to the amount of structural damage. However, the relationship between number of eccentric contractions, magnitude of structural damage and force decrement is not very well documented. Therefore we studied the effect of an increasing number of both isometric and eccentric (forced lengthening) contractions on histological parameters of muscle damage and maximal isometric force in an experimental in situ rat model. Tibialis anterior muscles of male Wistar rats were subjected to an increasing number of either isometric or eccentric contractions and were examined for histological markers of muscle damage. The present study shows that muscle damage increases progressively with the number of forced lengthening contractions. Maximal isometric torque was found to decline after both types of exercise. However, the decline after forced lengthening exercise was more pronounced. Only a weak relationship between percentage of histological muscle damage and isometric torque after forced lengthening contractions was found. The findings of the present study suggest that the decline in muscle force after eccentric exercise may partly be attributed to other factors than structural damage.     

Clinical significance of corpus callosum atrophy in a mixed elderly population

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.     

Fulminant falciparum malaria

A case of fulminant falciparum malaria with a 35% parasitaemia, shock and subcoma was treated successfully by using parenteral chemotherapy, exchange transfusion, dexamethasone, circulatory support and mechanical ventilation. Pathophysiology and complications of falciparum malaria are discussed. The treatment of severe malaria should aim for a fast reduction in parasitaemia and toxic products. An exchange transfusion can be additive to parenteral chemotherapy. Blocking the over-reacting cell-mediated immune response, aggressive shock treatment, prevention of secondary infections and maintaining normoglycaemia might reduce morbidity and mortality of fulminant falciparum malaria.     

Mechanism of arsenic-induced neurotoxicity may be explained through cleavage of p35 to p25 by calpain.

In recent studies we have demonstrated that arsenic (As) metabolites change the composition of neuronal cytoskeletal proteins in vivo and in vitro. To further examine the mechanism of arsenic-induced neurotoxicity with various arsenate metabolites (iAsV, MMAV and DMAV) and arsenite metabolites (iAsIII, MMAIII and DMAIII), we investigated the role of the proteolytic enzyme calpain and its involvement in the cleavage of p35 protein to p25, and also mRNA expression levels of calpain, cyclin-dependent kinase 5 (cdk5) and glycogen synthase kinase 3 beta (gsk3ss). A HeLa cell line transfected with a p35 construct (HeLa-p35) was used as a model, since all other proteins such as calpain, CDK5 and GSK3beta are already present in HeLa cells as they are in neuronal cells. HeLa-p35 cells were incubated with various As metabolites and concentrations of 0, 10 and 30 microM for duration of 4 h. Subsequently the cells were either lysed to study their relative quantification levels of these genes or to be examined on their p35-protein expression. P35-RNA expression levels were significantly (p<0.01) increased by arsenite metabolites, while p35 protein was cleaved to p25 (and p10) after incubation with these metabolites. The cleavage of p35 is caused by calcium (Ca2+) induced activation of calpain. Inhibition of calpain activity by calpeptin prevents cleavage of p35 to p25. These results suggest that cleavage of p35 to p25 by calpain, probably As-induced Ca2+-influx, may explain the mechanism by which arsenic induces its neurotoxic effects.     

Punctate white-matter lesions in the full-term newborn: Underlying aetiology and outcome

Background

Punctate white matter lesions (PWMLs) are small focal patches of increased signal intensity (SI) on T1- and decreased SI on T2-weighted magnetic resonance imaging (MRI). To date, there have been few reports of PWMLs in term born infants.

External validation of severity scoring systems for acute renal failure using a multinational database

OBJECTIVE: Several different severity scoring systems specific to acute renal failure have been proposed. However, most validation studies of these scoring systems were conducted in a single center or in a small number of centers, often the same ones used for their development. Therefore, it is not known whether such severity scoring systems may be widely applied. DESIGN: Prospective clinical investigation. SETTING: Intensive care units. PATIENTS: One thousand seven hundred and forty-two intensive care unit patients with acute renal failure who were either treated with renal replacement therapy or fulfilled predefined criteria. INTERVENTIONS: Demographic and clinical information and outcomes were measured. MEASUREMENTS AND MAIN RESULTS: Scores for four acute renal failure-specific scoring systems and two general scoring systems (Simplified Acute Physiology Score II and Sequential Organ Failure Assessment) were calculated, and their discrimination and calibration were tested with receiver operating characteristic curves and Hosmer-Lemeshow goodness-of fit-tests. For the receiver operating characteristic curves, blood lactate levels were also used as a reference. All scores had an area under the receiver operating characteristic curve <0.7 (Mehta 0.670, Liano 0.698, Chertow 0.610, Paganini 0.643, Simplified Acute Physiology Score II 0.645, Sequential Organ Failure Assessment 0.675, lactate 0.639). For scores that can calculate predicted mortality, the Hosmer-Lemeshow goodness-of-fit test showed poor calibration. CONCLUSIONS: None of the scoring systems tested had a high level of discrimination or calibration to predict mortality for patients with acute renal failure when tested in a broad cohort of patients from multiple countries. A large, multiple-center database might be needed to improve the discrimination and calibration of acute renal failure scoring system.