Relative importance of Microcystis abundance and diversity in determining microcystin dynamics in Lake Erie coastal wetland and downstream beach water.

AIMS: Microcystis population and microcystin (MC) dynamics were investigated in western Lake Erie coastal wetlands and downstream beach water. A three-dimensional (3-D) model was developed to quantify how Microcystis population size and structure affect MCs. METHODS AND RESULTS: Real-time PCR, denaturing gradient gel electrophoresis (DGGE) and enzyme-linked immunoabsorbent assay (ELISA) were used. A moderate-low level of Microcystis abundance and MCs were detected with a significant increase along the wetland flow and the spatiotemporal homogeneity of Microcystis populations. The proportion of toxigenic and nontoxgenic genotypes appeared to be more affected by the variation in two major Microcystis PC-IGS genotypes. MC dynamics was associated with the changing Microcystis population size and structure. The 3-D model showed that Microcystis population with greater Microcystis PC-IGS abundance (and simultaneously higher diversity) had more MCs. CONCLUSION: Microcystin variation was significantly affected by Microcystis population size and structure. The 3-D model also revealed the relative importance of Microcystis population size and structure in determining MCs in the Lake Erie costal wetland and downstream beach water. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enriches our understanding of Microcystis population and microcystin ecology in a western Lake Erie coastal wetland and downstream beach water. Our illustrative model brings a new perspective for understanding the ecological relationship between Microcystis population size and structure and MCs.

Tranexamic acid as adjunct therapy to bypassing agents in haemophilia A patients with inhibitors.

Haemophilia patients with inhibitors require bypassing agents (BPA) like activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) to control bleeds. Adjunct tranexamic acid (TXA) may improve haemostasis. The objective of this study was to investigate safety and haemostatic effect of TXA given in combination with BPA. Healthy volunteers (N = 5) and haemophilia inhibitor patients (N = 6) were enrolled in a prospective case crossover design. Controls were treated with TXA 20 mg kg(-1) orally (O.R.) Patients were treated with aPCC 75 IU kg(-1) intravenous (I.V.) on day 1 followed by TXA 20 mg kg(-1) O.R. combined with aPCC 75 IU kg(-1) I.V. on day 2. A 14-day washout occurred before crossover to rFVIIa 90 µg kg(-1) I.V. ±TXA. Safety evaluation and blood sampling processes were performed at baseline, 15, 30, 60, 120, 180 and 240 min post treatment. Primary outcome was maximum clot firmness (MCF) evaluated by whole blood thromboelastometry using a TF + tissue plasminogen activator-based assay. Healthy controls showed a 20-fold increase in MCF following TXA. Adjunct TXA to aPCC or rFVIIa induced a significant increase in MCF (P < 0.0001) reaching levels indistinguishable from healthy controls treated with TXA (P > 0.05). Infusion of aPCC or rFVIIa alone induced only 3-10 fold increase in MCF from baseline, with a decline in MCF starting after 60-120 min. TXA did not increase the endogenous thrombin potential. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed. Combination of aPCC or rFVIIa with TXA normalizes clot stability in haemophilia patients with inhibitor as compared to healthy controls. No clinical or laboratory adverse events were observed.

FXIII: mechanisms of action in the treatment of hemophilia A.

BACKGROUND: Hemophilia is characterized by abnormal thrombin generation and impaired clot stability. FXIII promotes clot stability and may be a useful adjunct treatment for hemophilia. OBJECTIVES: This study examined the clot stabilizing effects and safety of supra-physiological FXIII and explored the mechanisms via which FXIII exerts its effects in hemophilia A. METHODS: The effects of FXIII on clot formation and stability were examined using a thromboelastometry assay and blood samples collected from six patients with severe hemophilia A. The effect of FXIII on clot formation was also assessed using a murine model. The mechanisms of FXIII action in hemophilia A were explored by measuring thrombin generation, rates of FXIII activation and effects on clot permeability, pore size and fibrin fiber diameter. RESULTS: This study demonstrates that supra-physiological concentrations of FXIII stabilize clots in blood from patients with hemophilia by improving resistance to t-Pa-induced fibrinolysis even at low concentrations of FVIII (FVIII< 0.1 IU mL⁻¹, P < 0.05, anova). Addition of FXIII stoichiometrically up-regulates its activation, correcting the fibrin clot structure, reducing clot permeability and facilitating thrombin generation; FXIII significantly shortens ttPeak and lagtime (P < 0.05) in FVIII-deficient plasma, providing a novel explanation for its positive effects on clot stability and structure. The murine model indicates that supra-physiological FXIII is tolerated and does not significantly alter time to clot formation. CONCLUSION: The effects of FXIII on clot stability and physical clot structure are seen at low concentrations of FVIII, indicating that FXIII could be a useful treatment in a variety of clinical scenarios.

Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A.

BACKGROUND: N8-GP is a recombinant factor VIII (FVIII) with a site-directed glycoPEGylation for the purpose of half-life prolongation. OBJECTIVES: To evaluate the safety and pharmacokinetic profiles of N8-GP in comparison with those of the patients' previous FVIII products. PATIENTS/METHODS: This dose-escalation trial included previously treated patients with severe hemophilia A who received one of three dose levels (25, 50 or 75 U kg(-1) ) of N8-GP and FVIII product. Each dose escalation was preceded by safety and pharmacokinetic assessment. The trial was registered at www.clinicaltrials.gov (NCT01205724). RESULTS: Twenty-six patients each received one dose of their previous FVIII product followed by the same, single dose of N8-GP. N8-GP, at any tested dose, was well tolerated, with a low frequency of adverse events. No new inhibitors against FVIII or N8-GP and no binding antibodies against N8-GP developed during the trial. The pharmacokinetics of N8-GP were dose-linear. The incremental recovery of N8-GP was 0.025 [(U mL(-1) )/(U kg(-1) )]. The clearance was 1.79 mL(-1)  h(-1)  kg(-1) . The estimated time from dosing of 50 U kg(-1) N8-GP to a plasma activity of 1% was 6.5 days (range: 3.6-7.9 days). The mean terminal half-life of N8-GP was 19.0 h (range: 11.6-27.3 h), 1.6-fold longer than that of the patients' previous products. CONCLUSIONS: A single dose of up to 75 U kg(-1) N8-GP was well tolerated in patients with hemophilia A, with no safety concerns. N8-GP had a prolonged half-life, and FVIII:C activity remained at > 1% for longer than the patient's previous product. These results indicate that N8-GP has the potential to reduce dosing frequency during prophylaxis.

Novel management of anticoagulant resistant thrombotic hypodysfibrinogenaemia.

Individuals with hypodysfibrinogenaemia and recurrent thrombosis are rarely encountered and there is no consensus regarding long-term management. Guidelines available suggest that oral anticoagulants should be sufficient treatment, but when this fails to control thrombotic disease no further management strategies are reported. A novel approach to treatment has been developed and used for two individuals who experienced life-threatening thrombosis despite anticoagulation adherent to current guidelines. These two affected individuals consented to receive infusions of exogenous fibrinogen concentrate thrice weekly in addition to continuing warfarin (target INR 3-4). Both have been thrombosis free 36 and 18 months after starting this ongoing regime. This study suggests regular transfusions of fibrinogen concentrate may be a suitable treatment for anticoagulant resistant thrombotic hypodysfibrinogenaemia, but further research is required.

Comparative in vitro cytotoxicity study of carbon nanotubes and titania nanostructures on human lung epithelial cells.

The aim of this study is to assess in vitro cytotoxic effects of titania nanostructures and carbon nanotubes (CNTs) by exposing A549 lung epithelial cell line to these materials. Titania nanotubes (TiNTs) were grown by hydrothermal treatment of TiO(2) nanoparticles, followed by annealing them at 400°C. The titania nanostructures obtained on annealing (mixture of nanotubes and nanorods) were hollow and open ended, containing 3-5 layers of titania sheets, with an internal diameter ∼3-5 nm and external diameter ∼8-10 nm, and a specific surface area of 265 m(2)/g. As-supplied single walled (SWCNTs) and microwave plasma enhanced chemical vapour deposition (MPCVD) grown multi walled carbon nanotubes (MWCNTs) were used in this study. The lengths and diameters of the SWCNTs were 5-10nm and 0.5-3 nm respectively. The lengths and diameters of the MWCNTs were 25-30 µm and 10-30 nm respectively. The cell viability was evaluated using the MTT (3-(4,-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium) assay. No significant cytotoxic effects of titania nanostructures were observed over a period of a week of testing time, while the presence of CNTs in some cases demonstrated significant cytotoxic effects. Finally, possible reason of cytotoxicity is discussed in the light of microstructures of materials.

Factor XIII combined with recombinant factor VIIa: a new means of treating severe hemophilia A.

BACKGROUND: Abnormal thrombin generation is considered the key defect in hemophilia. Conventional treatment seeks to correct this using coagulation factor replacement or bypassing agents, for example recombinant factor VIIa (rFVIIa). Previous studies demonstrate abnormal FXIII activation in patients with hemophilia. FXIII activation is essential for formation of structurally normal, stable clots. OBJECTIVES: The present study challenges the hypothesis that in hemophilia the use of plasma-derived FXIII (pdFXIII) in combination with rFVIIa will produce a greater improvement in clot stability than promotion of thrombin generation alone. METHODS: Fourteen individuals with severe hemophila A were enrolled. Whole blood was spiked ex vivo with buffer, rFVIIa (2 µg mL(-1)) or rFVIIa (2 µg mL(-1)) plus pdFXIII (10 µg mL(-1)). Whole blood thromboelastometry assessed clot stability, after activation with tissue factor (TF) (0.15 pm) plus tissue-type plasminogen activator (tPa) (2 nm). The primary outcome measure of clot stability was area under the elasticity curve (AUEC). RESULTS: The combination of pdFXIII and rFVIIa significantly improved clot stability as measured by AUEC (P < 0.05) compared with rFVIIa alone. CONCLUSION: The use of pdFXIII resulted in superior clot stability compared with solely enhancing thrombin generation and we suggest that increasing thrombin generation alone fails to fully correct dysregulation of clot-stabilizing mechanisms associated with bleeding disorders. Hemorrhage control in hemophilia may be improved using clot stabilizing drugs. FXIII shows potential as a novel agent.

Relationship between erythrocyte GLUT1 function and membrane glycation in type 2 diabetes.

This paper investigates the effect of glycation on glucose transport in erythrocytes. Glucose transporter function, numbers and erythrocyte phosphorylation rates are simultaneously studied using 30 Caucasian patients with diabetes and 30 Caucasian control volunteers (mean +/- SD where P < or = 0.05; age 48 +/- 8 vs. 45 +/- 8 years [ns]; body mass index [BMI] 31 +/- 7 vs. 27 +/- 5 [P=0.035]; blood glucose 12 +/- 7 vs. 5 +/- 0.6 mmol/L [P=0.001]; HbA1c 8 +/- 2 vs. 5 +/- 0.3% [P=0.0001]; fructosamine 336 +/- 64 vs. 237 +/- 16 micromol/L [P=0.0001]; disease duration 13 +/- 11 years, respectively). Significant differences were found for glucose transporter function, with 3-O-methylglucose uptake rates (108 +/- 49 vs. 146 +/- 55 micromol/L/sec/10(12) cells [P=0.010]); D-glucose influx (64 +/- 30 vs. 117 +/- 45 micromol/L/sec/10(12) cells [P=0.0001]); and D-glucose net transport (31 +/- 22 vs. 74 +/- 55 micromol/L/sec/ 10(12) cells [P = 0.0001]). No differences were found for phosphorylation rates using 2-deoxyglucose (33 +/- 17 vs. 38 +/- 12 micromol/L/sec/10(12) cells [P=0.194]). The number of functional transporters using cytochalasin B studies measured via B(max), was not found to be significantly different between the groups (195 +/- 139 vs. 264 +/- 174 [P=0.206]). However, K(d) was lower for those with diabetes, suggesting higher binding affinity (12 +/- 11 vs. 32 +/- 25 nmol/L [P=0.006]). A negative correlation between HbAlc and D-glucose influx involving both groups was found (r=-0.670, P=0.0001). Glucose transport is shown to be decreased in people who have diabetes compared to normoglycaemic volunteers, whereas the number of glucose transporters is apparently unchanged; however, affinity for binding is increased.

Influence of human development and predators on nest survival of tundra birds, Arctic Coastal Plain, Alaska.

Nest predation may influence population dynamics of birds on the Arctic Coastal Plain (ACP) of Alaska, USA. Anthropogenic development on the ACP is increasing, which may attract nest predators by providing artificial sources of food, perches, den sites, and nest sites. Enhanced populations or concentrations of human-subsidized predators may reduce nest survival for tundra-nesting birds. In this study, we tested the hypothesis that nest survival decreases in proximity to human infrastructure. We monitored 1257 nests of 13 shorebird species and 619 nests of four passerine species at seven sites on the ACP from 2002 to 2005. Study sites were chosen to represent a range of distances to infrastructure from 100 m to 80 km. We used Cox proportional hazards regression models to evaluate the effects of background (i.e., natural) factors and infrastructure on nest survival. We documented high spatial and temporal variability in nest survival, and site and year were both included in the best background model. We did not detect an effect of human infrastructure on nest survival for shorebirds as a group. In contrast, we found evidence that risk of predation for passerine nests increased within 5 km of infrastructure. This finding provides quantitative evidence of a relationship between infrastructure and nest survival for breeding passerines on the ACP. A posteriori finer-scale analyses (within oil field sites and individual species) suggested that Red and Red-necked Phalaropes combined (Phalaropus fulicarius, P. lobatus) had lower productivity closer to infrastructure and in areas with higher abundance of subsidized predators. However, we did not detect such a relationship between infrastructure and nest survival for Semipalmated and Pectoral Sandpipers (Calidris pusilla, C. melanotos), the two most abundant shorebirds. High variability in environmental conditions, nest survival, and predator numbers between sites and years may have contributed to these inconsistent results. We recommend targeted management actions to minimize anthropogenic effects and suggest new research needed on this issue as expanding development is planned for the ACP of Alaska. In particular, we recommend research on demography of key predators and their importance with respect to nest survival, and experimental studies that better address challenges posed by high natural variability.

Pharmacokinetics, coagulation factor consumption and clinical efficacy in patients being switched from full-length FVIII treatment to B-domain-deleted r-FVIII and back to full-length FVIII.

Concerns have been raised regarding pharmacokinetic performance, efficacy and safety of B-domain-deleted recombinant FVIII (BDD rFVIII). The objective of this study was to perform a retrospective survey of half-life measurements, efficacy and safety in patients with severe haemophilia A, switching treatment from full-length factor VIII (FL FVIII) to BDD rFVIII and then back to FL FVIII. We hypothesized that half-life of FVIII would be equal regardless of product and that total factor consumption and bleeding frequency would be indistinguishable. We report on inhibitor development and outcome following surgery. Patients with severe haemophilia A, exposed to BDD rFVIII were identified from a database. A retrospective analysis of laboratory data and medical notes was undertaken. No significant difference was detected between the half-life measurements during the switch from FL FVIII (T/2 median 9.15 h, range 6.4-22) to BDD rFVIII (T/2 median 9.7, range 4.7-16.8) and back to FL FVIII (T/2 median 9.0, range 5.0-19.5). There was no significant difference in coagulation factor usage (BDD rFVIII median 4803 IU kg(-1) year(-1), range 659-11 304; FL FVIII median 5349, range 1691-10 146), nor bleeds. Eleven received BDD rFVIII to cover surgical procedures, with no reports of excess bleeding. Thirty-three patients received significant exposure to BDD rFVIII and one developed a low titre inhibitor. BDD rFVIII was found to be equivalent to other FVIII products in terms of pharmacokinetics, clinical efficacy and safety in this study group.

Flexible trainees in Scotland.

INTRODUCTION: Demand for flexible training is increasing. The contribution of such trainees to the trained medical workforce is not clear. METHODS: All full time and flexible trainees in Scotland were 'tracked' at the completion of training. RESULTS: 80% of flexible trainees took up a consultant post of which 93% were in Scotland. 82% of full time trainees took up a consultant post of which 80% were in Scotland. DISCUSSION: Flexible trainees become consultants at the same rate as their full time counterparts. They are commonly geographically tied and are therefore more likely to remain in Scotland and contribute to retention of doctors in this country.

Relationship of glycation, antioxidant status and oxidative stress to vascular endothelial damage in diabetes.

AIMS: To examine the inter-relationships of various microvascular pathogenic mechanisms in diabetic patients. METHODS: Patients with diabetes (n = 18) and non-diabetic subjects (n = 18) were studied. RESULTS: Blood markers of glycaemic control and glycation differed between the two groups (glucose 10.9 +/- 7.6 vs. 4.7 +/- 0.63 mmol/l, p < 0.01; HbA1c 7.0 +/- 1.3 vs. 4.5 +/- 0.3%, p < 0.001; glycated LDL 8.8 +/- 2.5 vs. 6.1 +/- 1.2%, p < 0.001) but plasma antioxidant status did not. LDL oxidation resistance, measured as lag time to maximum oxidation initiated by copper ions, was decreased in diabetes (58. +/- 14.3 vs. 76.3 +/- 21.5 min, p < 0.01). Both soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), markers of endothelial dysfunction, were significantly higher in diabetes (ICAM 491 +/- 128 vs. 403 +/- 131 micro g/l, p < 0.05; VCAM 546 +/- 157 vs. 393 +/- 106 micro g/l, p < 0.01). Linear correlations were significant between HbA1c and lag time of LDL oxidation (r = -0.39, p < 0.05), ICAM (r = 0.40, p < 0.05) and VCAM (r = 0.38, p < 0.05). LDL oxidizability correlated with vitamin C (r = 0.51, p < 0.01) but not any adhesion molecule. In multivariate analysis, both ICAM and VCAM correlated with HbA1c only (r(2) = 0.16, F = 6.3, p < 0.01; r(2) = 0.14, F = 5.4, p < 0.01 respectively). CONCLUSION: In diabetes, glycation, tissue oxidation and endothelial function are all abnormal and predisposing to microvascular complications but interrelationships are complex with glycation appearing most direct.

Increased non-transferrin bound iron in plasma-depleted SAG-M red blood cell units.

BACKGROUND AND OBJECTIVES: Non-transferrin bound iron (NTBI) is associated with increased morbidity in a number of transfusion-dependent disease states such as the severe haemoglobinopathies. We hypothesized that this may be related to excess NTBI present in plasma-depleted red blood cell units that are free of clear haemolysis. MATERIALS AND METHODS: The level of NTBI was determined using the bleomycin assay in samples from 20 stored plasma-depleted red cell units, at approximate 5-day intervals up to day 33 after donation. Forty units of fresh-frozen plasma (FFP) and 40 units of platelet concentrates were used as negative controls, and samples from 12 units of FFP were also serially assessed. RESULTS: Median [interquartile range (IQR)] NTBI was 0 microm (0-0.35) in samples taken from units 3-10 days after donation. Thereafter, the levels of NTBI increased, becoming significant (median 3.05; IQR: 0.05-6.7 microm) 17-22 days after donation. After 30 days, NTBI was detectable in all red cell units. NTBI was undetectable in platelet concentrates and FFP. CONCLUSIONS: Increased levels of NTBI become detectable 17-22 days after donation and increase further with storage time. This excess NTBI may promote bacterial infection in iron-loaded individuals.

Nutritionally induced adipose hypertrophy in young pigs is transient and independent of changes in the expression of the obese and peroxisome proliferator activated receptor genes.

Previous studies have shown that piglets weaned to a liquid milk replacer (MR), rather than a typical dry diet (DD) regimen, have improved growth rates and deposit more energy as body fat. In the present study, we used this model to determine whether changes in the expression of genes linked to the regulation of adiposity were related to the accelerated fat accretion. We also determined whether the increase in body fat was sustained throughout a substantial proportion of the growth curve. At weaning (19 plus minus 2 days of age), 96 piglets were placed in 12 replicate pens per diet (4 pigs per pen, 2 barrows and 2 gilts), and fed a liquid MR or conventional DD regimen for 5 weeks. Thereafter, 6 barrows and 6 gilts pigs from each diet were killed for determination of whole body chemical composition (less gastrointestinal contents). The remaining pigs were assigned randomly to weight target groups (60, 85, and 110 kg), placed in individual pens, and fed a conventional dietary regimen until killed at their respective weight targets for tissue sampling and determination of whole body chemical composition. Over the 5-week period in which the MR was fed, the growth rate of the pigs consuming the MR exceeded that of the pigs fed the DD by 36% (P <.05). Fat gain in these pigs was increased to 1.8 times that of the pigs fed the DD, and percentage body fat was 45% greater (P <.05). Acetyl Co-A carboxylase (ACC) activity (per mg of adipose extract protein) was not different between the two diet groups at the conclusion of the 5-week period, or at 110 kg body weight. During the MR period, actual protein gain was increased (P <.05) 22% in the pigs fed the MR as well. By 110 kg of body weight, body fat was reduced (P <.05) by 7.7% (total fat mass) and 8.3% (percentage of body weight basis) in the pigs fed MR vs. the DD group. The expression of the peroxisome proliferator activated receptors (PPAR) alpha and gamma was not influenced by diet or by body weight. Expression of the obese gene was independent of diet, but was greater (P <.09) in pigs at 110 kg body weight than at 60 kg. These data provide additional evidence that piglets weaned to liquid diets have greater rates of growth and deposit more body fat, but that this difference subsides quickly when a typical dry dietary regimen is imposed. Furthermore, the biochemical changes responsible for the increased adiposity are independent of changes in the expression of the obese or PPAR genes, at least at the mRNA level.

Reduced vitamin E antioxidant capacity in sickle cell disease is related to transfusion status but not to sickle crisis.

In homozygous sickle cell disease (SCD), decreased serum Vitamin E is present. Excessive transfusions may lead to iron overload. We hypothesised a relationship between the two and found that Vitamin E type antioxidant capacity was significantly lower in 30 SCD patients than in 30 age- and sex-matched controls (P < 0.001). Antioxidant capacity was lower in 10 transfused patients compared with 20 non-transfused patients (P < 0.001). Transfusional iron overload in SCD may increase the potential for oxidative damage, and low antioxidant capacity may compound this effect.

Vitamin E correlates inversely with non-transferrin-bound iron in sickle cell disease.

Decreased serum vitamin E levels are found in homozygous sickle cell disease (SCD). Excessive transfusions may lead high non-transferrin-bound iron (NTBI). Hypothesizing a relationship between the two, vitamin E (measured using high performance liquid chromatography) was significantly lower in 30 SCD patients than in 30 age-/sex-matched controls (P < 0.001), but NTBI (bleomycin assay) was higher (P < 0.001). Vitamin E was lower in 10 transfused patients than in 20 non-transfused patients (P < 0.001) with a significant inverse correlation between the NTBI and vitamin E (r = -0.58, P < 0.001). NTBI associated with iron overload in SCD may increase the potential for oxidative damage and low vitamin E activity may compound this effect.

Cognitive deficits associated with a recently reported familial neurodegenerative disease: familial encephalopathy with neuroserpin inclusion bodies.

BACKGROUND: We recently discovered an autosomal dominant disease causing a progressive dementia. The disease is caused by a point mutation in the gene coding for the serine protease inhibitor (ie, serpin) neuroserpin. The mutation results in an unstable neuroserpin protein that readily aggregates into intraneuronal inclusions that we identify as Collins bodies. The bodies are distributed throughout the cerebral hemispheres but are significantly more numerous in the cortex and the substantia nigra. We have named the disease familial encephalopathy with neuroserpin inclusion bodies (FENIB). OBJECTIVES: To describe the cognitive and neurophysiological changes exhibited by individuals with FENIB and to correlate the phenotypic expression of the disease with the neuropathological findings. DESIGN: Multiple case studies using neuropsychological assessment, electroencephalography (EEG), magnetic resonance imaging (MRI), and single-photon emission computed tomographic (SPECT) studies of family members were performed. Using these measures, we also compared family members in whom the mutation is present with family members in whom the mutation was absent to control for nonspecific familial factors. SUBJECTS: Nine individuals (5 women, aged 31-64 years; 4 men, aged 43-67 years) from 2 generations of family members related to the first reliably identified individual with symptoms of this disease. Symptoms, by self-report and reports of other family members, ranged from asymptomatic to severe dementia. Six of the 9 individuals carried the disease mutation. RESULTS: All subjects with the mutation demonstrated some cognitive changes, with the greatest demonstrated by subjects older than 40 years. The changes included restricted attention, concentration, and response regulation functions, reduced controlled oral fluency (word-list generation), and restricted visuospatial organization. In general, recall memory was not as affected as other cognitive domains. The most severely affected subject demonstrated global dementia with prominent frontal lobe features. Findings on SPECT showed anomalies limited to frontal areas in the less affected subjects and more global, patchy areas of hypoperfusion in the more severely affected subjects. The 3 oldest and most affected subjects demonstrated slowing on EEG findings. The MRI findings were noncontributory except in the 2 most severe cases, which showed global cortical atrophy. CONCLUSIONS: Cognitive changes in mildly to moderately affected subjects were characterized by deficits in frontal and frontal-subcortical area-dependent processes. Continued progressive deterioration of cerebral functions with relative sparing of recall memory suggests a unique dementia associated with this disease.

[Visual acuity and ocular diseases in aged residents of nursing homes: study of 219 persons in Orléans]. / Acuité visuelle et pathologie oculaire chez le sujet âgé résidant en maison de retraite: étude orléanaise sur 219 personnes.

PURPOSE: To measure the visual acuity and to determine the etiological causes of visual impairment in the elderly residing in nursing homes. METHODS: 219 elderly persons residing in nursing homes were examined in the residence. The ophthalmological examination consisted in a visual acuity measurement, a slit-lamp examination and a fundus examination. RESULTS: This study included 145 women and 74 men. Mean age was 79.1 years (range 41-101 years). Visual acuity could be measured in 181 subjects (82.6%): it was 1/10 or worse in the better eye in 23 of them (13%) and 2/10 to 3/10 in 36 patients (20%). In 21 (17.6%) out of the 119 patients aged over 74 years, visual acuity was 1/10 or worse in the better eye. Visual impairment significantly increased with age (p < 0.05). There was no difference between men and women in the prevalence of visual impairment. Among the 55 subjects with visual impairment, the main causes of vision loss were: cataract in 36 patients (66%), age-related macular degeneration in 9 patients (16%) and optic neuropathies in 5 patients (9%). Only one (2.8%) out of the 36 patients with cataract could be operated. CONCLUSION: The rate of visual impairment of people in nursing homes was higher than in corresponding age groups in the general population. The main cause of vision loss was cataract; however, only a few patients could benefit from an operation. These results confirmed that a systematic ophthalmologic examination should be performed before general health problems prevent patients from being operated.