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At least 127 records · Page 7Linked to original sources
PubMed2006

Atypical neuroleptics as a treatment of agitation and anxiety in Alzheimer's disease: risks or benefits.

Behavioral problems produce excess disability that can be potentially devastating in cognitively impaired patients. These behavioral symptoms can be a major cause of stress, anxiety and concern for caregivers. While psychotropic drugs are frequently used to control these symptoms, they have the potential for significant side effects, which include sedation, disinhibition, depression, falls, incontinence, parkinsonism and akathisias. On examination of the consequences of adverse events, somnolence, as well as postural instability and postural hypotension, have been noted. All patients with Alzheimer's disease (AD) and other progressive dementias will advance through stages of moderate-to-severe AD unless effective treatments suspend transition from mild deterioration to dementia, or competitive mortality truncates survival. Treatment trials suggest that these patients respond to both disease-modifying (such as inhibitors of cholinesterase and butirrylcholinesterase) and symptomatic (such as neuroleptics) agents. Relatively few studies have been conducted in this patient population, and more information regarding the type of behavioral disturbances exhibited, how best to measure them in this disabled population and their optimum treatment are urgently needed.

Alzheimer Disease↗
PubMed2001

Role of coenzyme Q10 in chronic heart failure, angina, and hypertension.

PURPOSE: Coenzyme Q10 (CoQ10) has a pathophysiologic role in many disease states. The purpose of this review is to provide recommendations regarding the safety, efficacy, and dosing of CoQ10 in the management of chronic heart failure (CHF), angina, and hypertension. DATA SOURCES: Literature pertaining to the safety and efficacy of CoQ10 specifically in cardiovascular indications was reviewed. We used relevant clinical trials, articles, reviews, and letters that were selected from a literature search of the MEDLINE database (1974-2000), Micromedex Healthcare Series, and the Natural Medicines Comprehensive Database. FINDINGS: Coenzyme Q10 administered orally has favorable actions in the described cardiovascular conditions and appears to be safe and well tolerated in the adult population. Issues concerning optimum target dosages, potential interactions, monitoring parameters, and the role of CoQ10 as a monotherapeutic agent need to be investigated further. Favorable effects of CoQ10 on ejection fraction, exercise tolerance, cardiac output, and stroke volume are demonstrated in the literature; thus, the use of CoQ10 as adjuvant therapy in patients with CHF may be supported. CONCLUSIONS: Coenzyme Q10 therapy in angina and hypertension cannot be substantiated until additional clinical trials demonstrate consistent beneficial effects. However, CoQ10 may be recommended as adjuvant therapy in selected patients with CHE At this time, CoQ10 should not be recommended as monotherapy or first-line therapy in any disease state.

Angina, Unstable↗
PubMed1998

Detection and utilization of single genes without DNA assays.

Quantitative traits are often assumed to be controlled by a large number of loci that each have a small effect. Under this assumption, the distribution of genotypic and phenotypic values can be adequately modeled by a multivariate normal distribution. Thus, most genetic analyses are based on mixed linear models. Evidence is accumulating, however, for the presence of loci that have large effects on traits of economic importance. If the genotypes for such loci can be observed without error, then--conditional on these observed genotypes--genotypic and phenotypic values follow a multivariate normal distribution, and data from very large pedigrees can be analyzed using a mixed linear model that includes the genotypic effects for these loci as fixed effects. However, when the major genotype is not observed, the genotypic and phenotypic values follow a mixture of multivariate normal distributions, and analyses based on fitting a mixed linear model may not be optimum, especially for populations undergoing selection and nonrandom mating. Several approaches are discussed for the genetic analysis of data when the major genotypes are not known.

Algorithms↗
PubMed1977

[T-cell subpopulations in mixed lymphocyte cultured. Model of T-cell interactions].

The present studies have shown that two subpopulations of thymus-dependent lymphocytes may act synergisticaly in the mixed lymphocyte reaction (MLR) in the mouse. One subpopulation was well represented in the young adult thymus and the other in lymph nodes. For optimum synergy, both populations must be allogeneic to the stimulator cells. Pretreatment of either population with mitomycin-C abolished synergy. In a cinetic study lymph node cells were proliferating before thymus cells. A mixture of thymus and lymph node cells (4:1) demonstrated a proliferation pattern like pure lymph node cells. Possibly, in MLC 3 cell types react, a T1- and T2-cell triggered by LD-antigens and a T-effector cell triggered by SD-antigens. These different T-cell subpopulations may interact in MLC.

Animals↗
PubMed1992

Familial breast cancer.

Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed.

Breast Neoplasms↗
PubMed1977

Rubella--a reappraisal.

Rubella infection is reviewed and new information about congenital infection, possible sources of infection in pregnant women and the optimum ages and population groups for rubella vaccination is considered. Investigations required to confirm a suspected and possibly 'silent' infection during pregnancy are outlined.

Adolescent↗
PubMed2002

Spurious results in therapeutic drug monitoring research.

Maximal correlation between measured blood concentration of a drug and an estimate of the area under the concentration-time curve (AUC) is widely used as criterion for the optimal blood sampling time-point in therapeutic drug monitoring (TDM) research. (More generally, the correlation between an estimate of AUC and a linear combination of several concentration measurements is considered, but the principles are the same.) This particular TDM research methodology is evaluated from a theoretical statistical perspective by considering a general nonspecific study. It is shown that the TDM research methodology produces spurious results because the optimal time-point is determined by irrelevant factors. Particularly, the sampling design is an important determinant. The sampling time-points are of course the only candidates for the optimal time-point, but they may also determine which candidate is optimal. In a special case, it is mathematically proven that any time-point except the first (trough level) can be made optimal by choosing the appropriate sampling design. This is probably true in all practical situations. The theoretical optimum is defined as the optimal time-point in the ideal theoretical sampling design where concentration measurements are made continuously in time. Hence, the theoretical optimum is independent of sampling designs, and the optimal time-point of a study is an approximation to the theoretical optimum. In a homogeneous study population, it can be proven, mathematically and under realistic assumptions, that the theoretical optimum is t(max). Particularly t(max), is the individual theoretical optimum. Heterogeneity of the study population can be an important determinant of the optimal time-point. In significantly heterogeneous study populations, the optimal time-point is usually extreme compared with the distribution of the individual optimal time-points in the population.

Algorithms↗
PubMed1991

DNA analysis of Duchenne and Becker muscular dystrophy using pERT87 genomic probes and dystrophin cDNA probes--establishing the optimum strategy for carrier diagnosis in the Japanese population.

DNA analysis was performed on 19 unrelated Duchenne muscular dystrophy (DMD) families and one Becker muscular dystrophy (BMD) family in Japan to determine their carrier status. The intragenic genomic probe pERT87 with its subclones 87-1, 87-8, and 87-15 were used together with five cDNA probes from the 5' end of the dystrophin gene. The tests with both a high polymorphism information content (P.I.C.) and a high observed P.I.C. were most effective, i.e., pERT87-1/XmnI, pERT87-15/XmnI, pERT87-8/TaqI, and pERT87-8/BstXI. These test combinations were useful in the Japanese population but pERT87-15/TaqI was not, although it was effective in Caucasians. Two additional test combinations of pERT87-1/MspI and pERT87-15/BamHI were highly useful in detecting restriction fragment length polymorphisms (RFLPs) when other tests were not informative. Carrier status could be determined in 18 out of 20 clients who were at risk for DMD/BMD carrier status from 20 families, similar to the rate of detection in Caucasians. The total detection rate of deletions was 74% with the five cDNA probes. Deletions were concentrated on two hot spots where 92% of all deletions were detected by only two probes, 1-2a and 8. Deletions were detected in two males with DMD who had none of the eight RFLPs tested. Our results emphasize the usefulness of DNA analysis with pERT87 genomic probes and cDNA probes. In addition, an optimum strategy for carrier detection in Japanese DMD/BMD families was proposed.

Chromosome Deletion↗
PubMed1994

Landscapes: complex optimization problems and biopolymer structures.

The evolution of RNA molecules in replication assays, viroids and RNA viruses can be viewed as an adaptation process on a 'fitness' landscape. The dynamics of evolution is hence tightly linked to the structure of the underlying landscape. Global features of landscapes can be described by statistical measures like number of optima, lengths of walks and correlation functions. The evolution of a quasispecies on such landscapes exhibits three dynamical regimes depending on the replication fidelity: Above the "localization threshold" the population is centered around a (local) optimum. Between localization and "dispersion threshold" the population is still centered around a consensus sequence, which, however, changes in time. For very large mutation rates the population spreads in sequence space like a gas. The critical mutation rates separating the three domains depend strongly on characteristics properties of the fitness landscapes. Statistical characteristics of RNA landscapes are accessible by mathematical analysis and computer calculations on the level of secondary structures: these RNA landscapes belong to the same class as well known optimization problems and simple spin glass models. The notion of a landscape is extended to combinatory maps, thereby allowing for a direct statistical investigation of the sequence structure relationships of RNA at the level of secondary structures. Frequencies of structures are highly non-uniform: we find relatively few common and many rare ones, as expressed by a generalized form of Zipf's law. Using an algorithm for inverse folding we show that sequences sharing the same structure are distributed randomly over sequence space. Together with calculations of structure correlations and a survey of neutral mutations this provides convincing evidence that RNA landscapes are as simple as they could possibly be for evolutionary adaptation: Any desired secondary structure can be found close to an arbitrary initial sequence and at the same time almost all bases can be substituted sequentially without ever changing the shape of the molecule. Consequences of these results for evolutionary optimization, the early stages of life, and molecular biotechnology are discussed.

Adaptation, Biological↗
PubMedDate not supplied

Optimum tool handle diameter for a cylinder grip.

The ideal diameter for a tool handle for males and females has been determined using an existing biomechanical model of the hand validated in previous works. The model estimates a 33-mm optimum diameter tool handle for the general population (males and females). When the optimum diameter for a tool handle is selected, the muscles exert the minimum force needed to hold the tool and perform gripping activities. Optimal handle design reduces the force required for gripping a tool, protects the underlying joint structures, and reduces the risk of developing cumulative trauma associated with repetitive task requiring high grip forces and awkward postures. This article provides a design parameter for optimal tool diameter to aid the therapist in the selection of assistive devices, built-up handles, or for the fabrication of a tool handle.

Biomechanical Phenomena↗
PubMed2006

On adaptive accuracy and precision in natural populations.

Adaptation is usually conceived as the fit of a population mean to a fitness optimum. Natural selection, however, does not act only to optimize the population mean. Rather, selection normally acts on the fitness of individual organisms in the population. Furthermore, individual genotypes do not produce invariant phenotypes, and their fitness depends on how precisely they are able to realize their target phenotypes. For these reasons we suggest that it is better to conceptualize adaptation as accuracy rather than as optimality. The adaptive inaccuracy of a genotype can be measured as a function of the expected distance of its associated phenotype from a fitness optimum. The less the distance, the more accurate is the adaptation. Adaptive accuracy has two components: the deviance of the genotypically set target phenotype from the optimum and the precision with which this target phenotype can be realized. The second component, the adaptive precision, has rarely been quantified as such. We survey the literature to quantify how much of the phenotypic variation in wild populations is due to imprecise development. We find that this component is often substantial and highly variable across traits. We suggest that selection for improved precision may be important for many traits.

Adaptation, Physiological↗
PubMed1987

Genetic differentiation of quantitative characters between populations or species. II: Optimal selection in infinite populations.

Using a new and more general genetic model called the discrete-allelic state model and assuming discrete-time process, the evolutionary changes of genetic variation of quantitative characters, controlled by a few loci, within and between populations during the process of genetic differentiation of populations or species, are studied under the effects of mutation and centripetal selection in infinitely large populations. While in a finite population and ignoring selection, the rate of change of additive genetic variance depends on mutation and effective population size, traits under optimal selection in infinitely large populations go through the dynamics of a rather complicated form depending on the relative intensities of selection and mutation. When a population, which has reached steady-state by mutation-selection balance, splits into two, in one of which the same optimum genotype holds but in the other the optimum shifts a few standard deviations away from the original optimum, the corresponding daughter population starts differentiating from its sister population by favouring certain class of mutant alleles and discarding others which were originally favoured. During this process of turn over of genes, both the intra- and inter-populational variances undergo a complicated change, and the ratio of the former to the latter is a non-linear function of time of divergence. This pattern is qualitatively very different from the case when selection is absent. The intra-population distribution of genotypic values, during this transition, is shown to deviate considerably from normality. The presence of linkage seems to retard the accumulation of intra-populational genetic variance. The implications of these results are discussed in comparison with the earlier findings of evolutionary models of quantitative traits.

Alleles↗
PubMed1992

Population pharmacokinetics of gentamicin in premature infants.

The population kinetics of gentamicin were studied in 97 newborn patients with a gestational age ranging between 28 and 43 weeks and a postnatal age ranging between 2 and 30 days undergoing routine therapeutic monitoring of their serum gentamicin levels. The individual kinetic analysis of serum drug levels was performed using a single-compartment model. The clearance and apparent distribution volume were calculated in each patient. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The effects of demographic variables on the clearance, distribution volume, and optimum daily dose of gentamicin were established using multiple linear regression. Gestational age is the best predictive variable of the clearance and the optimum dose/day in the whole population studied. In the premature infant patients, the predictive capacity increases with postconceptional age. Weight is a good predictive variable of all of the parameters, especially of the apparent distribution volume in the overall population of newborns. Analysis of the population kinetic behavior and optimum dose/day in each subgroup recommends that the interval of drug administration should be increased, keeping the same dose/day ratio, due to the tendency of the drug to accumulate its long half-life, especially in premature babies.

Birth Weight↗
PubMed2002

Evolutionary speed of species invasions.

Successful invasion may depend of the capacity of a species to adjust genetically to a spatially varying environment. This research modeled a species invasion by examining the interaction between a quantitative genetic trait and population density. It assumed: (I) a quantitative genetic trait describes the adaptation of an individual to its local ecological conditions; (2) populations far from the local optimum grow more slowly than those near the optimum; and (3) the evolution of a trait depends on local population density, because differences in local population densities cause asymmetrical gene flow. This genetics-density interaction determined the propagation speed of populations. Numerical simulations showed that populations spread by advancing as two synchronic traveling waves, one for population density and one for trait adaptation. The form of the density wave was a step front that advances homogenizing populations at their carrying capacity; the adaptation wave was a curve with finite slope that homogenizes populations at full adaptation. The largest speed of population expansion, for a dimensionless analysis, corresponded to an almost homogeneous spatial environment when this model approached an ecological description such as the Fisher-Skellam's model. A large genetic response also favored faster speeds. Evolutionary speeds, in a natural scale, showed a wide range of rates that were also slower compared to models that only consider demographics. This evolutionary speed increased with high heritability, strong stabilizing selection, and high intrinsic growth rate. It decreased for steeper environmental gradients. Also indicated was an optimal dispersal rate over which evolutionary speed declined. This is expected because dispersal moves individuals further, but homogenizes populations genetically, making them maladapted. The evolutionary speed was compared to observed data. Furthermore, a moderate increase in the speed of expansion was predicted for ecological changes related to global warming.

Adaptation, Biological↗
PubMedDate not supplied

Meeting the challenge of medication reactions in the elderly.

The number of elderly clients in most health care settings is increasing in direct proportion to the rapid aging of our general population. To plan and deliver optimum health care for elderly clients, nurses need to recognize this population's unique, special needs. One important aspect of quality care for older adults is managing their medications to assure the maximum beneficial results from medication therapy while avoiding adverse complications. Changes of aging will be examined in this article for their potential pharmacokinetic and pharmacodynamic impact. Incorporating this knowledge into practice will prepare professional nurses to act as change agents and advocates for increased awareness and sensitivity to actual or potential medication problems among all members of the health care team.

Aged↗
PubMed2003

Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs.

OBJECTIVE: To determine the effect of dietary n-6 to n-3 fatty acid ratios and alpha-tocopheryl acetate concentration on immune functions andT cell subpopulations in healthy dogs. ANIMALS: Thirty-two 7- to 10-year old female Beagles. PROCEDURE: For 17 weeks, dogs were fed food that contained low (1.4:1) or high (40:1) ratios of n-6 to n-3 fatty acids in combination with 3 concentrations of all rac-alpha-tocopheryl acetate (low, 17 mg/kg of food; medium, 101 mg/kg; high, 447 mg/kg). Dogs were inoculated twice with a keyhole limpet hemocyanin suspension at 13 and 15 weeks. RESULTS: After 12 weeks, dogs consuming low concentrations of alpha-tocopheryl acetate had lower percentages of CD8+ T cells, compared with dogs consuming medium or high alpha-tocopheryl acetate concentrations. Also, dogs consuming low alpha-tocopheryl acetate concentrations had higher CD4+ to CD8+ T cell ratios. On day 4 of week 15, the percentage of CD8+ T cells was highest in dogs fed medium concentrations of alpha-tocopheryl acetate, compared with other dogs; however, the CD4+ to CD8+ T cell ratio was higher only in dogs fed low concentrations of alpha-tocopheryl acetate with high concentrations of n-3 fatty acids. Dogs consuming low concentrations of n-3 fatty acids with medium concentrations of alpha-tocopheryl acetate had the largest delayed-type hypersensitivity (DTH) skin test response. CONCLUSIONS AND CLINICAL RELEVANCE: An optimum amount of dietary alpha-tocopheryl acetate concentration, regardless of the dietary n-6 to n-3 fatty acid ratio, stimulates the CD8+ T cell population. Effects of an optimum amount of dietary alpha-tocopheryl acetate concentration on the DTH response are blunted by dietary n-3 fatty acids.

Adjuvants, Immunologic↗
PubMed2006

Optimum blood sampling time windows for parameter estimation in population pharmacokinetic experiments.

Clinical trials requiring the collection of pharmacokinetic information often specify blood samples to be taken at fixed times. This may be feasible when trial participants are in a controlled environment such as in early phase clinical trials, however it becomes problematic in trials where patients are in an out-patient clinic setting such as in late phase drug development. In such a situation it is common to take blood samples when it is convenient for all involved and may result in data that are uninformative. This paper proposes an approach to pharmacokinetic study design that allows greater flexibility as to when blood samples can be taken and still result in data that allows satisfactory parameter estimation. The sampling window approach proposed in this paper is based on determining time intervals around the D-optimum pharmacokinetic sampling times. These intervals are determined by allowing the sampling window design to result in a specified level of efficiency when compared to the fixed times D-optimum design. Several approaches are suggested for dealing with this design problem.

Blood Specimen Collection↗