White matter predicts functional connectivity in premanifest Huntington's disease.

OBJECTIVES: The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. METHODS: Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. RESULTS: We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. INTERPRETATION: Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero-posterior dissociation that is in keeping with the caudo-rostral gradient of striatal pathology in HD.

Norton scale scores and 1-year mortality in elderly patients following lower limb amputations.

BACKGROUND: The Norton scale is used for assessing the risk of pressure ulcers. The association between low admission Norton scale scores (ANSS), complications and mortality in elderly patients following lower limb amputations has never been studied until now. OBJECTIVES: The aim of this study was to investigate if low ANSSs are associated with complications the 30-day and 1-year mortality in elderly patients following lower limb amputations. MATERIALS AND METHODS: The medical charts of 104 elderly (≥ 65 years) patients following lower limb amputations were studied for the following measurements: ANSS, demographics, comorbidities, complications during hospitalization, 30-day mortality and 1-year mortality. Complications included acute coronary syndrome, major bleeding, stroke, systemic infections, organ failure and thromboembolism. An ANSS ≤ 14 was considered as being low. RESULTS: Overall 54 (51.9%) patients underwent below-knee amputations and 50 (48.1%) patients underwent above-knee amputations. Most (n = 78; 75.0 %) patients were men and the mean age was 78.5 ± 7.9 years. Following the amputation 46 (44.2%) patients had complications other than pressure ulcers, 24 (23.1%) patients died within 30 days and 63 (60.6%) patients died within 1 year. A total of 61 (58.7%) patients had a low ANSS. The incidence of complications other than pressure ulcers, 30-day and 1-year mortality rates were higher in patients with a low ANSS relative to patients with a high ANSS. A regression analysis showed that 1-year mortality was independently negatively associated with ANSS (t = 2.629; p = 0.010). CONCLUSION: The Norton scale can be used for predicting 1-year mortality in elderly patients following lower limb amputations.

The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study.

BACKGROUND: Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being. METHOD: We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). RESULTS: Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions. CONCLUSIONS: Current subthreshold depressive symptoms in early HD are associated with microstructural changes - without concomitant brain volume loss - in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.

Sexual activity and erectile dysfunction in elderly men with angiographically documented coronary artery disease.

We studied the prevalence of erectile dysfunction (ED) in elderly men, aged 65 years or above, with coronary artery disease (CAD) documented by coronary angiography. A total of 123 men (112 men with CAD and 11 men without CAD), mean age 74.6+/-5.9 years, was included. To detect ED and assess its severity, all participants were asked to complete the Sexual Health Inventory for Males (SHIM) questionnaire. Lack of sexual activity was more prevalent among men with CAD relative to men without CAD (31.3 vs 0.0%). Among the sexually active men, ED was more prevalent among men with CAD relative to men without CAD (85.7 vs 72.7%). A general linear model showed that age was the only factor associated with SHIM scores among the sexually active men with CAD (P=0.001). Other factors, such as the number of occluded coronary arteries, diabetes mellitus, hypertension, smoking, various medications and marital status, were not associated with SHIM scores in elderly men with CAD. We conclude that lack of sexual activity and ED are very common in elderly men with CAD. Among the sexually active men with CAD, ED severity is associated only with age.

Increased erythrocyte aggregation in men with coronary artery disease and erectile dysfunction.

We studied the association between erythrocyte aggregation (EA) and erectile dysfunction (ED) in men with coronary artery disease (CAD). Men with CAD documented by coronary angiography filled the Sexual Health Inventory for Males questionnaire to detect ED and assess its severity. EA was evaluated by filming slides of blood smear. Low percentage of slide field covered by erythrocytes represented increased EA. Overall, 133 men with CAD, mean ages 62.4+/-12.2 years, were included: 100 (75.2%) with ED and 33 (24.8%) without ED. EA was increased among men with ED compared with men without ED (percentage of slide field covered by erythrocytes 66.7+/-14.7 vs 73.1+/-14.5%; P=0.03). After adjustment for age, diabetes mellitus, hemoglobin and hematocrit levels, EA was associated with ED severity (r=0.18; P=0.038). We conclude that EA is increased in men with CAD and ED. This finding may be relevant to the pathophysiology of ED in men with CAD.

Torsade de pointes induced by psychotropic drugs and the prevalence of its risk factors.

OBJECTIVE: To investigate all published case reports of torsade de pointes (TdP) induced by psychotropic drugs (PDs) in order to examine the prevalence of risk factors for TdP prior to the drug initiation. METHOD: We found 45 reports on 70 patients with TdP induced by PDs. Each report was analyzed for the presence of risk factors for TdP: female gender, heart disease, hypokalemia, high doses of offending agent, concomitant use of a QT interval prolonging agent, and a history of long-QT syndrome. RESULTS: Female gender was the most common risk factor for TdP (71.4%). The other studied risk factors were also frequently present (34.2-14.2%). Nearly all patients had at least one and 51 (73%) patients had >2 risk factors for TdP prior to PD initiation. CONCLUSION: We wish to raise the level of awareness of risk factors for TdP in the psychiatric community.

Serum lipids as minor determinants of the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with low grade inflammation and moderately increased serum lipids.

Both lipids and inflammation sensitive proteins have been reported to affect the aggregation of red blood cells yet their relative importance in this regard have not been determined. We have included high sensitive C-reactive protein, erythrocyte sedimentation, fibrinogen concentrations as well as various serum lipid concentrations and the degree of erythrocyte adhesiveness/aggregation in the peripheral blood in a linear regression analysis. Partial Pearson correlation coefficients were included as well. In a group of 674 individuals with various atherosclerotic risk factors, low grade inflammation and moderately increased serum lipids, a relatively low correlation was noted between red blood cell adhesiveness/aggregation and triglycerides concentrations. A negative correlation was noted for HDL cholesterol. None of the lipid variables turned significant in the regression analysis. In a group of individuals with atherosclerotic risk factors, low grade inflammation and moderately increased serum lipids, the degree of erythrocyte adhesiveness/aggregation in the peripheral blood correlates much better with the presence of inflammation sensitive proteins than with the presence of increased lipid concentrations.

Comparative analysis between dextran sulfate adsorption and direct adsorption of lipoproteins in their capability to reduce erythrocyte adhesiveness/aggregation in the peripheral blood.

The purpose of this study was to compare the degree of erythrocyte adhesiveness/aggregation (EAA) reduction of two low-density lipoprotein (LDL) apheretic procedures, namely direct adsorption of lipoproteins (DALI) and dextran sulfate adsorption (DSA). A significant (P < 0.001) reduction of EAA was noted in six hypercholesterolemic patients who underwent a total of 40 apheretic sessions and no difference was noted in the degree of EAA reduction by the two techniques. Thus. being a real-time and point-of-care test, the erythrocyte adhesiveness/aggregation test can be applied in relevant situations of acute ischemia, where therapeutic LDL apheresis could improve the hemorheology of individuals with increased concentrations of cholesterol and inflammatory sensitive proteins.

Sex differences in the expression of haemorheological determinants in individuals with atherothrombotic risk factors and in apparently healthy people.

BACKGROUND: Increased red cell aggregation can be detrimental, leading to slow capillary blood flow and tissue hypoxaemia. Sex differences in the degree of erythrocyte adhesiveness/aggregation in the peripheral blood have not been clearly shown. OBJECTIVES: To determine whether there are sex differences in the expression of erythrocyte adhesiveness/aggregation in the peripheral blood in individuals with atherothrombotic risk factors and in apparently healthy people. METHODS: From a cohort of 965 participants in the Tel Aviv Medical Centre inflammation survey, 192 pairs of different sex were matched for age, body mass index, hip and waist circumferences, cardiovascular risk factors, and the intake of active cardiovascular drugs. RESULTS: Women had an enhanced degree of red cell aggregation (p < 0.0005) as well as increased concentrations of inflammation sensitive proteins including fibrinogen and C reactive protein. Women had a lower haemoglobin concentration than men, but this did not affect the degree of erythrocyte adhesiveness/aggregation. CONCLUSIONS: The significant increase in red blood cell adhesiveness/aggregation in the peripheral blood of women with atherothrombosis could be relevant to the more eventful course that some women experience during and following acute ischaemic disease.

Capillary and venous leukocyte adhesiveness/aggregation to differentiate between viral and bacterial infection.

BACKGROUND: A simple capillary leukocyte adhesiveness/aggregation test (CAPLAAT) might be helpful in determining the intensity of inflammation in acute viral and bacterial infections. PATIENTS AND METHODS: We included 30 patients with acute bacterial infections, 14 with viral infections as well as 48 healthy controls. The leukocyte adhesiveness/aggregation test (LAAT) test was performed using a simple slide test and image analysis. RESULTS: The CAPLAAT had a similar discrimination power between bacterial and viral infections as both the white blood cell count (WBC) and the erythrocyte sedimentation rate (ESR). It was more sensitive than the WBC and the ESR (77%, 68% and 66%, respectively) for the detection of bacterial infections and had a comparable negative predictive value. By analyzing the size distribution of the aggregated leukocytes, we found that a venous leukocyte adhesiveness/aggregation test (VLAAT) of four cells and more had the best positive predictive value (94%) and specificity (95%) for diagnosis of an acute bacterial infection (from all the acute phase response variables examined). CONCLUSION: The CAPLAAT might be attractive for the detection of inflammation and for the assessment of its severity at points of care where the services of a clinical laboratory are not available around the clock.

The leukocyte adhesiveness/aggregation test (LAAT) conveys information of biological relevance and is not a result of chance collision. Something more than another hypothesis.

The leukocyte adhesiveness/aggregation test is a sensitive marker for the detection of inflammation and for the assessment of its intensity. This has been convincingly shown by several independent groups as well as in various models of infection/inflammation. However, it has not been settled whether the concomitant appearance of leukocytosis and aggregation is a result of chance collision or not. We recently examined a group of individuals with proven acute infection/inflammation who had absolutely the same number of white blood cells in the peripheral blood and found significantly enhanced leukocyte adhesiveness/aggregation in patients as opposed to control. These findings clearly demonstrate that the phenomenon of leukocyte adhesiveness/aggregation does not result from a simple chance collision. It probably conveys a message of biological relevance reflecting both the appearance of cell adhesive molecules during activation as well as the contribution of plasmatic sticky proteins.

Stability in a metapopulation model with density-dependent dispersal.

A spatially explicit metapopulation model with positive density-dependent migration is analysed. We obtained conditions under which a previously stable system can be driven to instability caused by a density-dependent migration mechanism. The stability boundary depends on the rate of increase of the number of migrants on each site at local equilibrium, on the intrinsic rate of increase at local level, on the number of patches, and on topological aspects regarding the connectivity between patches. A concrete example is presented illustrating the dynamics on the dispersal-induced unstable regime.

Synchronism in a metapopulation model.

We consider a spatially explicit meta-population model with interaction among the two nearest neighbors to relate, with a simple mathematical expression, chaos in the local, uncoupled, populations, the degree of interaction among patches, size of the meta-population, and the stability of the synchronized attractor. Since synchronism is strongly correlated with extinction, our results can provide useful information on factors leading to population extinction.

Intraocular lens implantation in Terrien's marginal corneal degeneration.

A patient with Terrien's corneal marginal degeneration and a previous trabeculectomy had planned extracapsular cataract extraction with intraocular lens implantation. A corneal incision was made with a diamond blade on the degeneration furrow superiorly and was closed with a 10-0 nylon double-running suture with keratoscopic control.

Results of unilateral medial rectus recession in high AC/A ratio esotropia.

Twenty-five patients with high accommodative convergence/accommodation (AC/A) ratios and near esotropia of 15 to 35 prism diopters were treated with a 6- to 8-mm unilateral medial rectus recession according to the near deviation. In 24 patients (96%), the esodeviation was aligned within 10 delta, with a follow up ranging from 3 to 7 years. Only one patient had greater than 10 delta of esotropia (14 delta), and none became exotropic. This procedure appears to be a safe and effective method in the treatment of esotropia with high AC/A ratios, in a selected group of patients.