Measuring attention in very old adults using the Test of Everyday Attention.

There is a need for validated measures of attention for use in longitudinal studies of older populations. We studied 249 participants aged 80 to 101 years using the population-based MOBILIZE Boston Study. Four subscales of the Test of Everyday Attention (TEA) were included, measuring attention switching, selective, sustained and divided attention and a neuropsychological battery including validated measures of multiple cognitive domains measuring attention, executive function and memory.

Pain and Cognitive Function Among Older Adults Living in the Community.

Background: Pain related to many age-related chronic conditions is a burdensome problem in elderly adults and may also interfere with cognitive functioning. The purpose of this study was to examine the cross-sectional relationship between measures of pain severity and pain interference and cognitive performance in community-living older adults.

Methods: We studied 765 participants in the Maintenance of Balance Independent Living Intellect and Zest (MOBILIZE) Boston Study, a population-based study of persons aged 70 and older.

Summation priming in aphasia: evidence for alterations in semantic integration and activation.

The present study used a lexical decision paradigm to study the summation of priming effects in normal and aphasic participants. The amount of priming produced by pairs of definitionally converging associative words was compared to the amount of priming produced by pairs of single associative words and non-words in two experiments in which the ISI between primes and targets varied from 200 ms (Experiment 1) to 600 ms (Experiment 2). Control subjects showed a pattern of additive summation priming at the short ISI and overadditive summation priming at the longer ISI.

Alterations in the dynamics of semantic activation in Alzheimer's disease: evidence for the Gain/Decay hypothesis of a disorder of semantic memory.

While it has been commonly assumed that a deficit in semantic memory underlies many of the clinical and cognitive features of early Alzheimer's disease (AD), there has been little agreement on what constitutes a proper theoretical description of this impaired system. Currently, most theories of this disorder fall into two categories: those that posit degraded semantic representations, and those that posit impaired retrieval operations with relatively intact semantic representations. It is argued that each position has both empirical and logical disadvantages that have prevented the development of a consensus on how to describe the pathology of semantic memory in AD.

Characterization of two naturally occurring mutations in the second epidermal growth factor-like domain of factor VII.

We investigated the mechanisms responsible for severe factor VII (FVII) deficiency in homozygous Italian patients with either Gly97Cys or Gln100Arg mutations in the second epidermal growth factor domain of FVII. Transient expression of complementary DNA coding for the mutations in COS-1 cells showed impaired secretion of the mutant molecules. Using stably transfected Chinese hamster ovary (CHO) cells, we performed pulse-chase labeling studies, immunohistochemistry, and experiments with inhibitors of protein degradation, showing that FVII-Cys97 did not accumulate intracellularly but was degraded in a pre-Golgi, nonlysosomal compartment by a cysteine protease.

Evidence for NO. redox form of nitric oxide as nitrergic inhibitory neurotransmitter in gut.

A nitric oxide (NO)-like product of the L-arginine NO synthase pathway has been shown to be a major inhibitory neurotransmitter that is involved in the slow component of the inhibitory junction potential (IJP) elicited by stimulation of nonadrenergic, noncholinergic nerves. However, the exact nature of the nitrergic transmitter, the role of cGMP, and the involvement of a potassium or a chloride conductance in the slow IJP remain unresolved. We examined the effects of soluble guanylate cyclase inhibitors LY-83583 and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), potassium-channel blockers and putative chloride-channel blockers diphenylamine-2-carboxylate (DPC) and niflumic acid (NFA) on the hyperpolarization elicited by an NO.

Severe factor VII deficiency due to a mutation disrupting an Sp1 binding site in the factor VII promoter.

We have identified a point mutation in the promoter of the factor VII gene responsible for a severe bleeding disorder in a patient from a large French-Canadian family with known consanguinity. The proband has an extremely low plasma level of factor VII antigen and factor VII coagulant activity (<1 percent of normal) and suffers from hemarthroses and chronic arthropathy. Sequencing of the patient's factor VII 5' flanking region, intron/exon junctions, and coding regions showed a homozygous point mutation, a C to G transversion at position -94 relative to the translation start site.

Detrusor contraction duration as a urodynamic parameter of bladder outlet obstruction for evaluating men with lower urinary tract symptoms.

Purpose: Recent studies suggest that detrusor contraction duration increases with bladder outlet obstruction and correlates with the American Urological Association (AUA) symptom index. Since the detrusor contraction duration may also depend on detrusor contractility and bladder volume, its use alone in characterizing bladder outlet obstruction is debatable. Therefore, we studied the relationship between detrusor contraction duration and bladder outlet obstruction, bladder capacity, detrusor contractility and symptoms to determine whether detrusor contraction duration is a useful parameter for characterizing bladder outlet obstruction in men with lower urinary tract symptoms.

The Arg353Gln polymorphism reduces the level of coagulation factor VII. In vivo and in vitro studies.

Factor VII levels are regulated by environmental and genetic factors. Two polymorphisms, a G-to-A transversion at nucleotide 10,976 resulting in Arg353Gln and a decanucleotide insert at position -323 in the 5'-flanking region of the factor VII gene, have been associated with a 20% to 25% reduction in plasma factor VII levels. However Arg353Gln almost always segregates on alleles containing the insert in UK and Italian populations, thereby making it impossible to independently evaluate the impact of Arg353Gln on factor VII levels in these ethnic groups.

Transbilayer movement of fully ionized taurine-conjugated bile salts depends upon bile salt concentration, hydrophobicity, and membrane cholesterol content.

Taurine-conjugated bile salts mediate rapid transmembrane flux of divalent cations, irrespective of whether bile salts and divalent cations are initially on the same or opposite side of the membrane. We therefore hypothesized that ionized bile salts can equilibrate between membrane hemileaflets. We quantitated bile salt binding to large unilamellar egg yolk phosphatidylcholine (EYPC) +/- cholesterol (Ch) vesicles under conditions in which one or both hemileaflets were initially exposed to bile salts.

Severe factor VII deficiency due to a mutation disrupting a hepatocyte nuclear factor 4 binding site in the factor VII promoter.

Although small deletions, splice site abnormalities, missense, and nonsense mutations have been identified in patients with factor VII deficiency, there have been no reports of mutations in the factor VII promoter. We investigated a girl with factor VII levels that were less than 1% of normal in association with a severe bleeding diathesis. The patient is homozygous for a T to G transversion that occurs 61 bp before the translation start site.

A Thr359Met mutation in factor VII of a patient with a hereditary deficiency causes defective secretion of the molecule.

We elucidated the genetic basis responsible for factor VII deficiency in an Italian woman with a severe bleeding diathesis. In the allele inherited from the patient's father, we identified a G to A mutation at nucleotide 6070 at the 5' splice site of intron 4 and a G to A substitution at nucleotide 10976 resulting in the Arg353Gln polymorphism. The maternal allele demonstrated a C to T substitution at nucleotide 10994 resulting in Thr359Met.

Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells.

Lipoxins are bioactive eicosanoids that are generated within the vascular lumen by leukocytes and transcellular biosynthetic routes during multicellular responses. Polymorphomuclear neutrophils (PMN) and endothelial cells express high affinity receptors for lipoxins, engagement of which invokes profiles of signaling events that differ from other lipid mediators. In this work, we report that lipoxins are potent inhibitors of PMN-endothelial cell interactions triggered by leukotrienes via dual-pronged actions with PMN and endothelial cells.

Determinants of coagulation activation in humans.

To evaluate the mechanism responsible for the generation of factor VIIa in vivo, we measured the levels of this enzyme after administering purified factor IX concentrates to patients with hemophilia B. Their factor VIIa levels were initially very low and gradually increased to normal, but there were no significant changes in the generation of factor Xa or thrombin. The administration of 10 mu g/kg body weight of recombinant factor VIIa to patients with factor VII deficiency increased the circulating levels 35-fold, but this only resulted in normalization of the activation of factor IX and factor X.

Low prevalence of the factor V Leiden mutation among "severe" hemophiliacs with a "milder" bleeding diathesis.

Patients with hemophilia A and B and factor levels than 1 percent of normal bleed frequently with an average number of spontaneous bleeding episodes of 20-30 or more. However there are patients with equally low levels of factor VIII or factor IX who bleed once or twice per year or not at all. To examine whether the presence of a hereditary defect predisposing to hypercoagulability might play a role in ameliorating the hemorrhagic tendency in these so-called "mild severe" hemophiliacs, we determined the prevalence of prothrombotic defects in 17 patients with hemophilia A and four patients with hemophilia B selected from 295 and 76 individuals with these disorders, respectively, followed at a large Italian hemophilia center.

Determinants of plasma factor VIIa levels in humans.

Several enzymes can activate factor VII in vitro, but the protease responsible for generating factor VIIa in vivo has not been determined. Using recombinant tissue factor that has undergone a COOH-terminal truncation, a sensitive functional assay has been established for measuring plasma factor VIIa levels. To evaluate the mechanism responsible for the generation of factor VIIa in vivo, we measured the levels of this enzyme after administering purified concentrates of factor IX and factor VIII to patients with severe deficiencies of these clotting factors.

Potential vascular roles for lipoxins in the "stop programs" of host defense and inflammation.

Eicosanoids are oxygenated products of arachidonic acid or other related 20-carbon polyunsaturated fatty acids that modulate diverse biologic processes, including leukocyte recruitment and activation, hemostasis, blood flow, ion transport, smooth muscle contraction, mucous secretion, cell growth, and stimulus-response coupling. Inflammatory, thrombotic, and ischemic vascular events are complex multicellular responses that involve interactions of circulating blood cells with each other and with components of the vessel wall. Here, we review evidence that lipoxygenase-derived eicosanoids, specifically leukotrienes (LT) and lipoxins (LX), are generated within the vascular lumen during cell-cell interactions in inflammation and thrombosis.

Management of patients with hereditary defects predisposing to thrombosis including pregnant women.

In general, the current recommendations for treating and prophylaxing thrombotic patients with hereditary defects are similar to those for thrombotic individuals without a defect. Determinations as to the need for long-term anticoagulation require that a clinical assessment be made regarding the relative benefit in preventing thrombotic episodes versus the risk of increased bleeding. With our newly found ability to identify genetic risk factors in a substantial fraction of patients with venous thrombosis and pulmonary embolism, it will be possible to perform rigorously designed studies to determine whether they should be managed with more prolonged or intense anticoagulation after a thrombotic event or more aggressive prophylactic regimens in high risk situations such as a total hip replacement.

Late-life spinal cord injury and aging with a long term injury: characteristics of two emerging populations.

Modern care of patients with spinal cord injury is leading to greater numbers of individuals surviving into old age and the emergence of a cohort that has sustained injury at an advanced age. The clinical characteristics of either group of patients has not been well characterized. Analyses from the Aging with a Long-Term Disability Research Program database, which is enriched by the presence of a high quality Spinal Cord Injury Service, revealed a population of 510 recently assessed individuals with a mean age of 50 years, ranging from 16 to 84 years.

Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism.

The precise role of the American Urological Association (AUA) symptom index in the management of benign prostatic hyperplasia (BPH) is not well established. The AUA symptom index has been recommended only for quantifying the symptoms of BPH but not for its diagnosis. However, to our knowledge the ability to discriminate obstructive from nonobstructive BPH using the AUA symptom index has never been investigated.

Lipoxygenase product formation and cell adhesion during neutrophil-glomerular endothelial cell interaction.

Leukotriene (LT) and lipoxin (LX) levels were monitored in ionophore-stimulated coincubations of polymorphonuclear neutrophils (PMN) and microvascular kidney glomerular endothelial cells (GEN) to determine the profile of lipoxygenase (LO) products generated during cell-cell interactions and the relative contributions of transcellular pathways to LO product biosynthesis in this setting. LTB4 and LTC4 were the major products formed, as determined by reverse-phase high-performance liquid chromatography and radioimmunoassay. LTB4 and LTC4 levels were increased by 23 and 185%, respectively, in coincubations of PMN and GEN, compared with incubations of PMN alone.

Molecular analysis of Polish patients with factor VII deficiency.

We analyzed the mutations in patients from 10 Polish kindreds with a bleeding diathesis due to factor VII deficiency. Patients from eight families had plasma levels of factor VII coagulant activity (VII:C) and factor VII antigen (VII:Ag) that were less than 4% of normal. The coding sequence of the factor VII gene was amplified from genomic DNA by polymerase chain reaction (PCR).

Pulmonary embolism after cardiac surgery.

Objectives: We examined the incidence of pulmonary embolism after cardiac surgery.

Background: Because venous thromboembolism is considered to be an uncommon complication after cardiac surgery, its incidence was documented in a consecutive series of 1,033 patients who underwent cardiac surgery over a 5-year period.

Methods: Parallel cohorts of patients in a tertiary referral center were evaluated and the incidence of pulmonary embolism was compared in subgroups of patients undergoing coronary bypass surgery, valve surgery and combined procedures.