Region-specific decline of cerebral glucose metabolism in patients with frontotemporal dementia: a prospective 18F-FDG-PET study

OBJECTIVE: The aim of this study was to examine the pattern of glucose uptake and the changes over time of metabolic deficits in patients with frontotemporal dementia (FTD). METHODS: 10 patients who had received the clinical diagnosis of FTD underwent positron emission tomography scanning at the time of their first examination (baseline) and at follow-up (after 17.1 +/- 6.0 months). For statistical analysis, we used the SPM 99 software. First, we compared the data of the patients at baseline with an age-matched healthy control group. Second, we compared glucose uptake at follow-up with baseline measurements. RESULTS: Compared with normal controls, FTD patients showed significant metabolic deficits primarily in frontal cortical areas, but also in the caudate nuclei and the thalami. At follow-up, a significant progression of metabolic deficit was exclusively observed in the orbitofrontal parts of the frontal lobe and in the subcortical structures. DISCUSSION: These findings demonstrate that the clinical progression in patients with FTD is accompanied by a region-specific decline in cerebral glucose metabolism.     

Prion protein codon 129 polymorphism and risk of Alzheimer disease

The authors investigated the PRNP Met129Val polymorphism in 1,393 subjects including 482 patients with Alzheimer disease (AD) and two independent control groups. In patients, PRNP Met homozygosity conferred increasing risk with decreasing age at onset (onset: 61 to 70 years, n = 151, p = 0.02, odds ratio [OR] = 1.72, 95% CI = 1.2 to 2.53; onset: < or =60 years, n = 138, p = 0.013, OR = 1.92, 95% CI = 1.31 to 2.87), whereas no association was obtained in patients with onset at older than 70 years. The results suggest involvement of the prion protein in the pathogenesis of early-onset AD.     

Laser trabecular sclerosis for chronic hypotony after vitreoretinal surgery

PURPOSE: To perform a pilot study of laser trabecular sclerosis (LTS) for chronic ocular hypotony after vitreoretinal surgery. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Three patients with chronic hypotony after vitreoretinal procedures underwent LTS. All patients had undergone complex vitreoretinal surgery with attached retinas postoperatively but with persistent hypotony and poor vision. INTERVENTION: Laser trabecular sclerosis was performed in a fashion similar to laser trabeculoplasty, using a 100-microm spot, 800 to 1000 mW power at 0.1 seconds, and applying heavy confluent treatment in >/=1 sessions throughout the angle where trabecular meshwork was visible. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), best spectacle-corrected visual acuity, and complications were studied. RESULTS: In 1 patient, a single session of LTS was followed by an increase in IOP of approximately 4 mm, with subjective and objective improvement in vision. A second patient exhibited improvement in IOP and visual acuity after 3 sessions of LTS. A third patient underwent 3 sessions of LTS without improvement in IOP or vision. CONCLUSION: Given the limitations of this small series, including the lack of a randomized prospective design, it is not possible to determine the safety or efficacy of LTS, but this study does suggest that this procedure could play a therapeutic role in some patients with chronic symptomatic hypotony after complex intraocular surgery. Further study is warranted.     

Presynaptic effects of moxonidine in isolated buffer perfused rat hearts: role of imidazoline-1 receptors and alpha2-adrenoceptors

Numerous studies support the concept that centrally acting antihypertensive drugs, such as imidazolines, mediate sympathoinhibition not only via activation of central nervous alpha2-adrenoceptors (alpha2-AR) but also via imidazoline-1 receptors (I1-R). An additional presynaptic involvement in sympathetic neurotransmission of imidazolines, via I1-R independent of alpha2-AR, is still controversial and remains to be clarified in the heart. Concentration response curves on endogenous norepinephrine (NE) overflow evoked by stimulation of epicardial postganglionic sympathetic nerves in isolated buffer-perfused rat hearts were performed for brimonidine, moxonidine, rauwolscine, 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane (AGN192403), and efaroxan. To unmask an I1-R-mediated effect of moxonidine, hearts were pre-exposed in additional experiments with brimonidine or rauwolscine with or without AGN192403 or efaroxan, respectively. Moxonidine reduced stimulated NE overflow (log EC50: -6.15 +/- 0.14). AGN192403, a selective ligand at I1-R, had no influence on the dose-response curve of moxonidine (log EC50: -6.01 +/- 0.25). After pre-exposure to brimonidine [ stimulation 1 (S1) + stimulation 2 (S2); 10(-5) M], the inhibitory action of moxonidine was potentiated compared with control (32.0 +/- 2.8 versus 73.13 +/- 3.0%) and completely abolished with AGN192403 or efaroxan. This effect was also totally inhibited by pre-exposure with indomethacin (10(-7) M) and tricyclodecan-9-yl-xanthogenate (D-609), an inhibitor of phosphatidylcholine-selective phospholipase C (PC-PLC; 10(-7) M). Conversely, moxonidine was without modulating efficacy under alpha2-AR-blockade by rauwolscine. In summary, we demonstrate that moxonidine reduces NE release independently of I1-R, demonstrating the prominent effect of alpha2-AR in cardiac tissue under basal conditions. We also demonstrate that I1-R are involved in NE release under conditions of alpha2-AR-stimulation involving both a pathway of prostaglandins and PC-PLC.     

Validity of the Leg-O-Meter, an instrument to measure leg circumference

The objective of this study was to validate the Leg-O-Meter measure against the clinical assessment of edema made by physicians using data from a 1-year follow-up study of unselected patients with chronic venous disease of the leg (CVDL). The Leg-O-Meter consists of a tape measure fixed to a stand attached to a small board on which the patient is in standing position. Its reliability has been shown to be above 97%. Data from the Venous Insufficiency Epidemiologic and Economic Study (VEINES) were used: 1,521 patients from France, Belgium, Italy, and Quebec (Canada) who spontaneously consulted a physician between 1994 and 1995 with a complaint resulting from venous problems of the legs were included. Baseline variables included leg circumference measurements using the Leg-O-Meter; physicians were also asked to diagnose edema and report it as present or absent on each leg. Clinical edema and leg circumferences were assessed again 3 to 6 months after the baseline visit and 12 months after baseline. The tape measure of the Leg-O-Meter was fixed at 13 cm from the floor. The first and last assessments were used to evaluate the variation in edema during the follow-up period. Clinical variation in edema status was assessed as follows: improved, if edema was diagnosed at baseline but not at the final visit; unchanged, if edema was diagnosed at both visits; and worsened, if there was no diagnosis of edema at baseline but a diagnosis of edema was made at the final visit. Variation in measured edema was classified as improved if there was a decrease in leg circumference of more than 1 cm between baseline and final evaluation; unchanged, if the difference in leg circumference was between plus or minus 1 cm between the 2 assessments; and worsened, if there was an increase in leg circumference greater than 1 cm between the 2 assessments. Data-driven cut-off points were also used: 1.3 cm and 1.5 cm. Sensitivity and specificity of the Leg-O-Meter using physician diagnosis as "gold standard" were calculated. In addition, receiver operating characteristics (ROC) curves were calculated by using the 3 different leg circumference cut-off points in order to determine the accuracy of the Leg-O-Meter to detect changes in edema. The overall accuracy of the Leg-O-Meter was 0.84 (standard error (se) = 0.06). Accuracy was greater when 1.5 cm was used as a cut-point. The Leg-O-Meter is an objective, reliable, and standardized instrument to assess patients over time. A change of 1.5 cm between 2 measurements gives a valid estimate of improvement or worsening of edema, when compared to physicians' diagnosis. The Leg-O-Meter is also sensitive to any changes in leg circumferences, which is an advantage over the clinical evaluation of edema.     

The measurement of sense of competence in caregivers of patients with dementia

BACKGROUND: In the context of a cohort study on the socio-economic consequences of dementia in Belgium, we evaluated the validity, reliability and feasibility of the French version of the Dutch Sense of Competence questionnaire (SCQ), and of its short version (the SSCQ), in caregivers of demented patients The questionnaire was based on Zarit's burden interview and on a theoretical family-crisis model. METHODS: Construct validity was evaluated by factor analysis and by comparison of the results with those of the original SCQ study. Reliability was evaluated by Cronbach's alpha and by item-total correlations. Feasibility was assessed by a standardized index of missing values. RESULTS: The three domains found in the original SCQ were identified by factor analysis: consequences of involvement in care for the personal life of the caregiver, satisfaction with one's own performance as a caregiver and satisfaction with the elderly person as a recipient of care. The mean scores were similar to those in the original study, except for the consequences for personal life. Cronbach's alpha for both the SCQ and the SSCQ exceeded the 0.70 criterion. Two of the 27 items did not meet the item-total correlation criterion; the SSCQ items all met the criterion. The standardised index of missing values was deemed acceptable. CONCLUSIONS: The French versions of the SCQ and the SSCQ are valid and reliable. Like the Dutch version, the French version of the SCQ can be a useful outcome measure for the evaluation of intervention studies and the SSCQ is suitable for the daily practice.     

Benzene metabolites antagonize etoposide-stabilized cleavable complexes of DNA topoisomerase IIalpha

Chronic exposure to benzene is associated with hematotoxicity and acute myelogenous leukemia. Inhibition of topoisomerase IIalpha (topo II) has been implicated in the development of benzene-induced cytogenetic aberrations. The purpose of this study was to determine the mechanism of topo II inhibition by benzene metabolites. In a DNA cleavage/relaxation assay, topo II was inhibited by p-benzoquinone and hydroquinone at 10 microM and 10 mM, respectively. On peroxidase activation, inhibition was seen with 4,4'-biphenol, hydroquinone, and catechol at 10 microM, 10 microM, and 30 microM, respectively. But, in no case was cleavable complex stabilization observed and the metabolites appeared to act at an earlier step of the enzyme cycle. In support of this conclusion, several metabolites antagonized etoposide-stabilized cleavable complex formation and inhibited topo II-DNA binding. It is therefore unlikely that benzene-induced acute myelogenous leukemia stems from events invoked for leukemogenic topo II cleavable complex-stabilizing antitumor agents. (Blood. 2001;98:830-833)     

Galantamine demonstrates efficacy and safety in elderly patients with Alzheimer disease

Alzheimer disease (AD) treatment guidelines state that cholinergic agents are not cost-effective in patients with more severe disease. Because many physicians may deem an older patient unlikely to respond to treatment, older AD patients may remain untreated. Galantamine (Reminyl), a novel cholinergic agent, is effective in mild to moderate AD. This post hoc analysis of pooled phase III galantamine clinical trials was designed to assess whether older (> or =80 years) and younger (< or =79 years) AD patients experience similar benefits with galantamine based on changes in the ADAS-cog and CIBIC-plus. Mean ADAS-cog scores for older patients treated with galantamine 24 mg/day significantly improved versus baseline and versus placebo at month 3. Cognitive improvement was maintained versus placebo at month 6; the ADAS-cog score for placebo patients dropped below baseline at month 6. Change in CIBIC-plus for galantamine was significantly different from placebo at months 5 to 6. Mean ADAS-cog score in older patients taking galantamine for 12 months remained above baseline. The score for patients taking placebo for 6 months before switching to galantamine did not differ significantly from baseline at 12 months but was lower than in patients receiving galantamine for 12 months. Incidence of adverse events in patients > 80 years was similar to that in the overall study population. Galantamine maintained cognitive and global function in patients > 80 years with mild to moderate AD for at least 5 to 6 months and cognitive efficacy for 12 months. Prescribing approved therapies such as galantamine for older patients with AD is recommended.