[Embrace, a model for integrated elderly care]. / SamenOud, een model voor geïntegreerde ouderenzorg: studieprotocol van een gerandomiseerde studie naar de effectiviteit betreffende patiëntuitkomsten, kwaliteit van zorg, zorggebruik en kosten.

UNLABELLED: Ongoing growth in health care expenditures and changing patterns in the demand for health care challenge societies worldwide. The Chronic Care Model (CCM), combined with classification for care needs based on Kaiser Permanente (KP) Triangle, may offer a suitable framework for change. The aim of the present study is to investigate the effectiveness of Embrace, a population-based model for integrated elderly care, regarding patient outcomes, service use, costs, and quality of care. METHODS: The CCM and the KP Triangle were translated to the Dutch setting and adapted to the full elderly population living in the community. A randomized controlled trial with balanced allocation was designed to test the effectiveness of Embrace. Eligible elderly persons are 75 years and older and enrolled with one of the participating general practitioner practices. Based on scores on the INTERMED-Elderly Self-Assessment and Groningen Frailty Indicator, participants will be stratified into one of three strata: (A) robust; (B) frail; and (C) complex care needs. Next, participants will be randomized per stratum to Embrace or care as usual. Embrace encompasses an Elderly Care Team per general practitioner practice, an Electronic Elderly Record System, decision support instruments, and a self-management support and prevention program - combined with care and support intensity levels increasing from stratum A to stratum C. Primary outcome variables are patient outcomes, service use, costs, and quality of care. Data will be collected at baseline, twelve months after starting date, and during the intervention period. DISCUSSION: This study could provide evidence for the effectiveness of Embrace.

Autosomal recessive cerebellar ataxias: the current state of affairs.

Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, and the genetic heterogeneity often complicate the clinical management of such patients. Despite the steady increase in newly discovered ARCA genes, many patients with a putative ARCA cannot be genotyped yet, proving that more genes must be involved. This review presents an updated overview of the various ARCAs. The clinical and genetic characteristics of those forms with a known molecular genetic defect are discussed, along with the emerging insights in the underlying pathophysiological mechanisms.

The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer's disease from non-Alzheimer's dementia.

BACKGROUND: Amyloid beta(40) (Abeta(40)) is the most abundant Abeta peptide in the brain. The cerebrospinal fluid (CSF) level of Abeta(40) might therefore be considered to most closely reflect the total Abeta load in the brain. Both in Alzheimer's disease (AD) and in normal aging the Abeta load in the brain has a large inter-individual variability. Relating Abeta(42) to Abeta(40) levels might consequently provide a more valid measure for reflecting the change in Abeta metabolism in dementia patients than the CSF Abeta(42) concentrations alone. This measure may also improve differential diagnosis between AD and other dementia syndromes, such as vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). OBJECTIVE: To investigate the diagnostic value of the CSF Abeta(42)/Abeta(40) ratio in differentiating AD from controls, VaD, DLB and FTD. METHODS: We analysed the CSF Abeta(42)/Abeta(40) ratio, phosphorylated tau(181) and total tau in 69 patients with AD, 26 patients with VaD, 16 patients with DLB, 27 patients with FTD, and 47 controls. RESULTS: Mean Abeta(40) levels were 2850 pg/ml in VaD and 2830 pg/ml in DLB patients, both significantly lower than in AD patients (3698 pg/ml; p<0.01). Abeta(40) levels in AD patients were not significantly different from those in controls (4035 pg/ml; p=0.384). The Abeta(42)/Abeta(40) ratio was significantly lower in AD patients than in all other groups (p <0.001, ANCOVA). Differentiating AD from VaD, DLB and non-AD dementia improved when the Abeta(42)/Abeta(40) ratio was used instead of Abeta(42) concentrations alone (p<0.01) The Abeta(42)/Abeta(40) ratio performed equally well as the combination of Abeta(42), phosphorylated tau(181) and total tau in differentiating AD from FTD and non-AD dementia. The diagnostic performance of the latter combination was not improved when the Abeta(42)/Abeta(40) ratio was used instead of Abeta(42) alone. CONCLUSION: The CSF Abeta42/Abeta40 ratio improves differentiation of AD patients from VaD, DLB and non-AD dementia patients, when compared to Abeta42 alone, and is a more easily interpretable alternative to the combination of Abeta42, p-tau and t-tau when differentiating AD from either FTD or non-AD dementia.

SPG10 is a rare cause of spastic paraplegia in European families.

BACKGROUND: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. OBJECTIVE: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype. PATIENTS AND METHODS: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families. RESULTS: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory-motor neuropathy was detected by neurophysiology studies. CONCLUSIONS: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy.

Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype.

We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurological abnormalities are only present in 2. This family shows that intermediate repeat lengths can be pathogenic and may predispose for restless legs and peripheral nerve disorder.

Carbohydrate Reserve and Dark Carbon Fixation in the Brown Macroalga, Laminaria hyperborea.

Tissue discs originating from young, growing blade areas and from adult, mature frond regions of the brown macroalga Laminaria hyperborea (Fosl.) Gunn. (Phaeophyceae, Laminariales) were investigated with particular regard to photosynthesis, dark respiration, dark carbon fixation, and carbohydrate reserves. It was found that the mannitol/laminaran reserve of the young, developing blade meets the requirements of dark respiratory metabolism for only 7-10d at 10±2 °C under continuous darkness. A concomitant decrease in the potential for (ß-carboxylation of phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (EC 4.1.1.32) occurred along with the depletion of the stored carbohydrate. Restoring the intracellular pool of reserve carbohydrates by photosynthesis and by feeding of exogenously supplied mannitol resulted in a short term recovery of the rates of dark fixation. These findings support the view that (i) in the dark the substrate of (ß-carboxylation is mainly derived from mannitol (along with glycolytic degradation of laminaran) and (ii) the young blade is not able to maintain its own carbon balance under the environmental conditions during midwinter and early spring, but relies on a carbon flow from the old blade.

Photorespiration and ß-carboxylation in brown macroalgae.

Photorespiration has been assayed in a variety of marine macroalgae by the Warburg oxygen inhibitory effect and the percentage(14)C-labeling of glycine and serine. It was found that particularly the members of the brown macroalgae examined, such asFucus andLaminaria (Phaeophyceae), show a rather weak response to high O2 partial pressure. This observation is attributed to the appreciably high potential for ß-carboxylation via PEP-carboxykinase, generally occurring in brown seaweeds.

Carbon assimilation by different developmental stages of Laminaria saccharina.

Various stages of the life cycle of the marine brown alga Laminaria saccharina (L.) Lamour. (Laminariales, Phaeophyta) including male and female gametophytes, female gametes, zygotes and young sporophytes of different age were investigated for their potentials of carbon dioxide ((14)CO2) fixation. Rates of photosynthesis attain the same order of magnitude in all stages. Photosynthetic (14)CO2-fixation is accompanied by a substantial light independent carbon assimilation. This is confirmed by rate determinations of the equivalent carboxylating enzymes present in the plants, ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) and phosphoenolpyruvate carboxokinase (EC 4.1.1.32) as well as by chromatographic analyses of the appropriate [(14)C]-assimilate patterns.

Longitudinal profiles of carbon dioxide fixation capacities in marine macroalgae.

Fucus serratus L., Fucus spiralis L., and Fucus vesiculosus L. (Fucales, Phaeophyceae) as well as Laminaria digitata (Huds.) Lamour., Laminaria hyperborea (Gunn.) Fosl., and Laminaria saccharina (L.) Lamour. (Laminariales, Phaeophyceae) have been investigated for the distribution of enzymic CO(2) fixation capacities via phosphoenolpyruvate carboxykinase (EC 4.1.1.32) (PEP-CK) and via ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) (RubP-C) in different regions of the thalli. The maximum of PEP-CK activity is found to be confined to the growing regions of the algae, while the activity of RubP-C achieves its highest values in the entirely differentiated parts of the fronds. These findings are confirmed by the results of photosynthetic and light-independent (dark) carbon assimilation as determined by in vivo(14)CO(2) fixation. The physiological significance of these differential patterns of carboxylation patterns is discussed with respect to the ontogenetic stage and the chemical constitution of the different thallus parts.

Carboxylating enzymes and pathway of photosynthetic carbon assmilation in different marine algae-Evidence for the C4-pathway?

Experiments on short-term photosynthesis in H(14)CO3 (-) (2-5 s) using various species of different algal classes resulted in predominant (14)C-labelling (>90% of total (14)C-incorporation) of phosphorylated compounds. The percentage of malate and aspartate usually accounts for distinctly less than 10% of the total (14)C-labelling. These findings are consistent with data from enzymatic analyses, since 97-100% of the carboxylation capacity is due to ribulose-1.5-biphosphate carboxylase (EC 4.1.1.39) in Rhodophyceae and Chlorophyceae. Phaeophyceae are generally characterized by considerable activity of phosphoenolpyruvate carboxykinase (EC 4.1.1.32): at least 10% of carboxylation is confined to this enzyme. Similar ratios are obtained when rates of photosynthesis and of light-independent CO2-fixation are compared. Activity of phosphoenolpyruvate carboxylase (EC 4.1.1.31) could not be detected in the species investigated. The results are discussed with emphasis on the pathway of photosynthetic carbon assimilation in marine algae.

Correlations between photosynthetic enzymes, CO2-fixation and plastid structure in an albino mutant of Zea mays L.

An albino seedling of Zea mays L. was investigated for its potential for CO2-assimilation. In the mesophyll the number, dimensions and fine structure of chloroplasts are drastically reduced but to a lesser extent in the bundle sheath. Chlorophyll concentration is zero and carotenoid concentration almost zero. Albinism also exerts a strong influence on the stroma of bundle sheath chloroplasts; ribulose-1.5-biphosphate carboxylase (EC 4.1.1.39) activity and glyceraldehyde-3-phosphate dehydrogenase (NADP) (EC 1.2.1.13) activity is not detectable. The C4-enzymes phosphoenolpyruvate carboxylase (EC 4.1.1.31) and malate dehydrogenase (decarboxylating) (EC 1.1.1.40) and the non-photosynthetic linked enzymes malate dehydrogenase (NAD) (EC 1.1.1.37), aspartate-2-oxoglutarate aminotransferase (EC 1.1.1.37), aspartate-2-oxoglutarate aminotransferase (EC 2.6.1.1.) and glyceraldehyde-3-phosphate dehydrogenase (NAD) (EC 1.2.1.1.) are present in the albino seedling with activities comparable to those in etiolated maize seedlings. The potential for CO2 fixation of the albino seedlings exceeds that of comparable dark seedlings considerably. The results are discussed with regard to enzyme localization of the C4 pathway of photosynthesis.

(14)C-Assimilate pattern and kinetics of photosynthetic (14)CO 2-assimilation of the marine red alga Bostrychia scorpioides.

Occurrence and metabolism of dulcitol and sorbitol in the marine red alga Bostrychia scorpioides (Huds.) Mont. (Ceramiales: Rhodomelaceae) were investigated. Both hexitols are rapidly (14)C-labelled during photosynthesis in a H(14)CO3-seawater medium and are accumulated at comparable rates. The absolute quantity amounts to about 3.2% on a dry weight basis; the percentage of (14)C-labelling after 60 min is 30% for dulcitol and 40% for sorbitol. Additionally small amounts of free [(14)C] glucose were found. Pulse labelling experiments and changes in specific activity provide evidence that both hexitols are rapidly available respiratory substrates, which, however, are probably not interconvertible with polymeric compounds. Some chemotaxonomic aspects are discussed.

[Localization of mannitol biosynthesis in the marine brown alga Fucus serratus]. / Lokalisation der Mannitbiosynthese in der marinen Braunalge Fucus serratus.

Tips of fronds of Fucus serratus L. were exposed to H(14)CO3 in the light for periods of 10, 30, 60, and 180s, fixed in petrol ether at-70° C, and subsequently lyophilized. Pheoplasts (=chloroplasts) were isolated using the nonaqueous technique of Thalacker et al. (1959). After extraction and chromatography percentage (14)C activity and distribution of individual photoassimilates between pheoplasts and other compartments of assimilating cells were analyzed. Eighty percent of [(14)C]-phosphate esters were found within the pheoplasts after 10s (14)C-assimilation, whereas only 25% were found there after 30s. After 10s [(14)C] mannitol is almost totally localized within the plastids, but after 180s the major part has been localized outside the pheoplasts. On the basis of these data the pheoplasts are regarded to be the only sites of primary mannitol biosynthesis during photosynthesis in Fucus.

[CO2-fixation and translocation in benthic marine algae : I. Kinetics of (14)CO 2-assimilation in Laminaria saccharina]. / CO2-Fixierung und Stofftransport in benthischen marinen Algen : I. Zur Kinetik der (14)CO 2-Assimilation bei Laminaria saccharina.

When discs punched out of the median part of the phylloid of Laminaria saccharina Lamour. were exposed to H(14)CO3 (-) in the light for periods of 10 sec to 10 min, (14)C was rapidly incorporated into various photosynthetic products. As compared with dark fixation, (14)C-photosynthesis increased exponentially during the first 60 sec of incubation in H(14)CO3 (-). Fixation rates were found to be 76 µmol CO2·dm(-2)·h(-1) or 100 µmol CO2·mg(-1) chlorophyll a·h(-1). Eighty-five per cent of the total (14)C assimilated after 10 sec was fixed in phosphoglycerate and in the sugar monophosphates, 2% in the sugar diphosphates, and only 3.5% in malate and aspartate. While the radioactivity of malate and aspartate only rose to a constant level, the percentage of the total (14)C in phosphoglycerate and-to a lower extent-that in the sugar monophosphates rapidly decreased with the duration of light exposure. Simultaneously, mannitol and glycine+serine became labelled with 43% and 32% respectively of the total (14)C after 10 min light fixation. In the dark, the percentage of the total (14)C in malate decreased with the time of H(14)CO(2-)-incubation, while there was a remarkable increase in radioactivity of aspartate and glutamate. Within 60 min darkness no labelling of mannitol was found.From the present results it is concluded that the photosynthetic carbon cycle first described by Bassham and Calvin operates in Laminaria saccharina.