Variation in stream network relationships and geospatial predictions of watershed conductivity.

Secondary salinization, the increase of anthropogenically-derived salts in freshwaters, threatens freshwater biota and ecosystems, drinking water supplies, and infrastructure. The various anthropogenic sources of salts and their locations in a watershed may result in secondary salinization of river and stream networks through multiple inputs. We developed a watershed predictive assessment to investigate the degree to which topology, land-cover, and land-use covariates affect stream specific conductivity (SC), a measure of salinity.

Spatial Convergence in Major Dissolved Ion Concentrations and Implications of Headwater Mining for Downstream Water Quality.

Spatial patterns in major dissolved solute concentrations were examined to better understand impact of surface coal mining in headwaters on downstream water chemistry. Sixty sites were sampled seasonally from 2012 to 2014 in an eastern Kentucky watershed. Watershed areas (WA) ranged from 1.

Age, Sex, and Gene Expression Score identifies a symptomatic, nondiabetic male patient as being at high risk of obstructive coronary artery disease.

In October 2015, a 74-year-old Caucasian male patient (past medical history of hyperlipidemia, paroxysmal atrial fibrillation, hypertension, and hypothyroidism) presented to the cardiologist for follow-up outpatient evaluation of exertional chest pain. The patient had recently been seen at the Emergency Department for the same complaint. At that time, the patient's cardiac markers, EKG, and pharmacological nuclear stress testing were all reported as normal.

Resection of a Giant Left Atrial Appendage Aneurysm via Limited Thoracotomy.

A left atrial appendage aneurysm is a rare cause of atrial arrhythmia in a young adult. Resection of the aneurysm is uniformly recommended in order to prevent thromboembolism and stroke. In patients without evidence of clot within the aneurysm, operative resection via a limited thoracotomy provides a safe and effective alternative to median sternotomy with cardiopulmonary bypass.

Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans.

This study sought to examine the feasibility of prolonged assessment of acetylcholinesterase (AChE) activity in the cerebrospinal fluid (CSF) of volunteers and to test the hypothesis that rivastigmine (ENA-713; Exelon, Novartis Pharma AG, Basel, Switzerland) selectively inhibits AChE in CSF in humans at a dose producing minimal inhibition of the peripheral enzyme. Lumbar CSF samples were collected continuously (0.1 mL x min(-1)) for 49 hours from eight healthy volunteers who took either placebo or a single oral dose of rivastigmine (3 mg).

Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of Alzheimer's disease.

Rivastigmine (ENA 713, or carbamoylatine) is an acetylcholinesterase (AChE) inhibitor with brain-region selectivity and a long duration of action. Both preclinical studies and studies in human volunteers have shown that rivastigmine induces substantially greater inhibition of AChE in the central nervous system (CNS) compartment than in the periphery (40% inhibition of central AChE compared with 10% inhibition of plasma butylcholinesterase in healthy volunteers). Moreover, rivastigmine preferentially inhibits the G1 enzymatic form of AChE, which predominates in the brains of patients with Alzheimer's disease (AD).

Dose-dependent CSF acetylcholinesterase inhibition by SDZ ENA 713 in Alzheimer's disease.

Introduction: This study evaluates the activity of SDZ ENA 713, a centrally-selective acetylcholinesterase (AChE) inhibitor, in the cerebral spinal fluid (CSF) of patients with Alzheimer's disease (AD), and its relationship to central and peripheral pharmacokinetic parameters.

Methods: Eighteen AD patients were enrolled in this open-label, multiple-dose study. Patients were titrated in 1 mg bid/week increments to target doses of 1, 2, 3, 4, 5, or 6 mg bid SDZ ENA 713.

Plasma sulfoconjugated dopamine levels are normal in patients with autonomic failure.

Plasma levels of norepinephrine (NE), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA), dopamine (DA), and dihydroxyphenylacetic acid (DOPAC)--all of which are free catechols--and sulfoconjugated DA (DASO4) were determined in 14 normal subjects and 18 patients with neurogenic orthostatic hypotension caused by either multiple system atrophy (MSA) (n = 11) or pure autonomic failure (n = 7). All free catechols were normal in patients with MSA, whereas NE, DHPG, DA, and DOPAC levels were significantly lower in patients with pure autonomic failure. The levels of DA-SO4, however, did not statistically differ among the three groups.

Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes.

Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities. The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios.

Biochemical and pharmacologic assessment of autonomic function.

Autonomic failure produces distinct pathophysiological abnormalities that differ according to the site and nature of the lesion(s). Although the anatomic organization and processes mediating chemical neurotransmission in the autonomic nervous system facilitate clinical investigation, limited access to the central compartment hampers evaluation of central neurotransmitter metabolism and neuropeptide function. As illustrated in the discussions of noradrenergic and cholinergic function, several indirect strategies have been used to assess the biochemical and neuropharmacologic consequences of autonomic dysfunction.

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3.

Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans.

Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.

Alzheimer's disease cerebrospinal fluid antibodies display selectivity for microglia. Investigations with cell cultures and human cortical biopsies.

Previous investigations demonstrated that the cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients contains antibodies that recognize specific neuronal populations in the adult rat central nervous system (CNS). These findings suggest a pathogenic role for immunological aberrations in this disorder. To determine if antibodies may provide a means to differentially diagnose the dementias, CSF from a diversified dementia population was screened against the developing rat CNS and a cell culture system.

Cerebrospinal fluid microglial antibodies: potential diagnostic markers for immune mechanisms in Alzheimer's disease.

Hallmark lesions of Alzheimer's disease (AD) are filled with reactive immunocompetent microglia, suggesting that immunological aberrations may participate in the pathophysiology of this disorder. Microglia may participate in the initial stages of neurodegeneration before the onset of dementia. If immune mediated processes are closely linked to neuronal breakdown it would be of importance to have a reliable means to detect these processes.

Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD.

Serum- and bradykinin-induced calcium transients in familial Alzheimer's fibroblasts.

The calcium-sensitive photoprotein, aequorin, was used to examine serum- and bradykinin-induced transient increases in free cytosolic calcium ions in skin fibroblasts from 10 individuals with early onset familial AD (FAD), including four who were biopsied before their clinical symptoms would allow a diagnosis of AD, 2 individuals with late onset FAD, 8 at-risk but nonsymptomatic individuals, and 13 controls. The data show that (a) among controls, the peaks of the calcium transients increase in height as a function of donor age; (b) transients induced by 10% serum, 10 nM bradykinin (BK) or 100 nM BK were generally lower in FAD fibroblasts, including those from donors in the early stages of the disease, than in age-matched control cells; (c) such transients are reduced in cells from a proportion of the nonsymptomatic, at-risk individuals. Thus, serum- and BK-induced calcium transients are reduced in fibroblasts from both early and more advanced stage FAD donors and perhaps even from donors who are presymptomatic carriers of the defective gene.

Olfactory dysfunction in the Shy-Drager syndrome.

The aetiology of the Shy-Drager syndrome (multiple system atrophy) is unknown. We reported previously a preliminary association between environmental-occupational risk factors and Shy-Drager syndrome. To further investigate this relationship, we evaluated olfactory function in eight patients in different stages of disease.

Cerebellar excitatory and inhibitory amino acid receptors in multiple system atrophy.

We studied excitatory and inhibitory amino acid binding sites autoradiographically in control and multiple system atrophy (MSA) cerebella. Within the dentate nucleus (DN) of MSA specimens, we found a significant increase in the level of GABAA, benzodiazepine, and metabotropic binding sites compared with controls. In the granule cell layer, kainate, N-methyl-D-aspartate, and GABAA binding sites were all decreased significantly in MSA specimens compared with controls.

Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees.

Studies of activated microglial cells and macrophages using Alzheimer's disease cerebrospinal fluid in adult rats with experimentally induced lesions.

Previous investigations have shown that cerebrospinal fluid from Alzheimer's disease patients contains antibodies that recognize the amoeboid microglia--a nascent and active form of microglia in the developing rat brain [McRae et al. (1991) Neuroscience 41, 739-752]. The present study extended this to show that the same cerebrospinal fluid from Alzheimer's disease patients also labeled the activated microglia and macrophages induced experimentally in adult central nervous system.