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Longitudinal assessment of deficit unawareness in Alzheimer's disease.

Longitudinal progression of impaired deficit awareness across varied functional domains was evaluated in 28 patients diagnosed with probable Alzheimer's disease (AD). Unawareness, as measured by patient-caregiver rating discordance, was first assessed in reference to patient memory, health status, self-care skills, anxiety, depression and irritability. The identical protocol was then repeated an average of 16.4 months later. Results indicated that, compared with caregiver ratings, patients tended to underestimate their deficits across functional domains. Patient-caregiver rating discrepancies were most pronounced in judgment of memory and self-care decline, indicating domain-specific differences in degree of unawareness. However, patient-caregiver rating discrepancies increased on most measures from time 1 to time 2 with no differences in the magnitude of these increases, suggesting a nonspecific longitudinal progression of unawareness. Although unawareness of deficits increased with time, longitudinal change in unawareness was not related to other disease and demographic variables such as age, education, age at onset, or duration of illness.

Activities of Daily Living↗

Mixed effects logistic regression models for longitudinal binary response data with informative drop-out.

A shared parameter model with logistic link is presented for longitudinal binary response data to accommodate informative drop-out. The model consists of observed longitudinal and missing response components that share random effects parameters. To our knowledge, this is the first presentation of such a model for longitudinal binary response data. Comparisons are made to an approximate conditional logit model in terms of a clinical trial dataset and simulations. The naive mixed effects logit model that does not account for informative drop-out is also compared. The simulation-based differences among the models with respect to coverage of confidence intervals, bias, and mean squared error (MSE) depend on at least two factors: whether an effect is a between- or within-subject effect and the amount of between-subject variation as exhibited by variance components of the random effects distributions. When the shared parameter model holds, the approximate conditional model provides confidence intervals with good coverage for within-cluster factors but not for between-cluster factors. The converse is true for the naive model. Under a different drop-out mechanism, when the probability of drop-out is dependent only on the current unobserved observation, all three models behave similarly by providing between-subject confidence intervals with good coverage and comparable MSE and bias but poor within-subject confidence intervals, MSE, and bias. The naive model does more poorly with respect to the within-subject effects than do the shared parameter and approximate conditional models. The data analysis, which entails a comparison of two pain relievers and a placebo with respect to pain relief, conforms to the simulation results based on the shared parameter model but not on the simulation based on the outcome-driven drop-out process. This comparison between the data analysis and simulation results may provide evidence that the shared parameter model holds for the pain data.

Analgesics↗

On the analysis of mixed longitudinal growth data.

Mixed longitudinal growth data consists of several observations on a characteristic over a limited age range for each individual in a study. This data is then combined to model growth over the total age range of all individuals in the study. The limited data collected on each individual precludes a subject-specific approach to modelling so that a population-based approach must be used. Here we propose a method for the analysis of mixed longitudinal data using linear models constructed from cubic splines to model both the mean and variance curves of an observed characteristic. The method is illustrated on growth in height and head circumference for children in a recently collected mixed longitudinal data set concerning the growth of Victorian schoolchildren, where particular concern was the timing of growth spurts and increases in variability.

Adolescent↗

Longitudinal cohort analysis of lethal prostate cancer progression in transgenic mice.

PURPOSE: Human prostate cancer is variably lethal, shows heterogeneous progression, and exhibits a spectrum of histopathology. Traditional rodent models of prostate cancer lack these characteristics. An alternative, autochthonous model of prostate cancer consists of transgenic mice which develop prostate cancer due to prostatic expression of SV40 T antigen. Lethal progression of such cancers in individual mice has not been previously characterized. Studies were undertaken to characterize the longitudinal progression of prostate cancers in these transgenic mice. METHODS: A prospective longitudinal cohort study was undertaken to characterize prostate cancer volume, progression, lethality, and histological heterogeneity in a transgenic mouse model of prostatic adenocarcinoma. Fifty-one transgenic mice were followed prospectively to determine the age at onset of palpable tumor and age at cancer-related death. Tumor volume was followed longitudinally by magnetic resonance imaging (MRI) in a subset of these mice and lethal cancers were evaluated by histopathology. RESULTS: Primary tumors became palpable at 10-38 weeks of age. Palpable tumors always preceded lethal progression. Cancer death followed 2-9 weeks later, and age at cancer death varied from 24 to 39 weeks of age. The histopathological changes were heterogeneous. Primary tumors were detectable by MRI before they became detectable by palpation. MRI showed that, analogous to human prostate cancers, volume of early stage primary tumors did not necessarily predict age at cancer death. CONCLUSION: Prostate cancer in transgenic mice mimics heterogeneic tumor progression in human prostate cancer, providing a uniquely relevant pre-clinical model. Tumor detection by MRI and palpation are valid surrogate measures of tumor progression in this model.

Animals↗

Strategies to enhance internal validity in multi-center longitudinal research.

Lack of standardized data collection procedures in multi-center longitudinal research poses potential threats to the internal validity of the study. This article addresses several key issues in data collection that can affect the results of longitudinal research. The authors describe these issues in relation to the study currently in progress and cite specific strategies used during data collection to reduce or eliminate data collection inconsistencies. Use of these strategies is not limited to longitudinal, nonexperimental causal models. Outcomes managers and clinical nursing researchers may find some of the strategies useful to enhance the internal consistency of experimental and nonexperimental cross-sectional research.

Bias↗

The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men.

BACKGROUND: The observation that dehydroepiandrosterone (DHEA) concentrations decrease markedly with age has led to the hypothesis that declining DHEA concentrations may contribute to age-related changes in cognition. In the United States, DHEA is widely available as an over-the-counter supplement that individuals are using in an effort to ameliorate age-related cognitive and physical changes. OBJECTIVE: To investigate the relationship between age-associated decreases in endogenous DHEA sulfate (DHEA-S) concentrations and declines in neuropsychological performance in a prospective, longitudinal study. METHODS: The subjects were 883 men from a community-dwelling volunteer sample in the Baltimore Longitudinal Study of Aging. The men were aged 22 to 91 years at the initial visit, and they were followed up for as long as 31 years (mean, 11. 55 years), with biennial reassessments of multiple cognitive domains and contemporaneous measurement of serum DHEA-S concentrations. Outcome measures were the results of cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency tests, and measures of visuomotor scanning and attention. Serum DHEA-S concentrations were determined by standard radioimmunoassay. RESULTS: Neither the rates of decline in mean DHEA-S concentrations nor the mean DHEA-S concentrations within individuals were related to cognitive status or cognitive decline. A comparison between the highest and lowest DHEA-S quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA-S concentration by more than a factor of 4 for a mean duration of 12 years. CONCLUSION: Our longitudinal results augment those of previous prospective studies by suggesting that the decline in endogenous DHEA-S concentration is independent of cognitive status and cognitive decline in healthy aging men.

Adult↗

Longitudinal muscle of muscularis externa in human and nonhuman primate colon.

The idea that the longitudinal muscle of the muscularis externa of the colon is confined to the colonic teniae in the monkey and human is a common conceptual error. Forty-six colon specimens taken from human and nonhuman primates were reviewed histologically and the distribution and structure of the longitudinal muscle were evaluated. We found that the longitudinal muscle forms a complete coat around the colon although it is considerably thicker in the region of the teniae coli. In addition to its anatomic importance, this observation has implications for the physiology of colon muscle and for certain current hypotheses concerning the etiology of diverticulitis.

Animals↗

The inferior longitudinal fasciculus: a reexamination in humans and monkeys.

The inferior longitudinal fasciculus is commonly considered to be a long association fiber bundle interconnecting the occipital and temporal lobes. Based on blunt dissections of human and monkey brains, we have found that the only long fiber bundle common to both the occipital and temporal lobes is the geniculostriate pathway (i.e., optic radiations), located within the external sagittal stratum. In addition, our autoradiographic experiments indicate that the pathway from the occipital to the temporal cortex in monkeys consists of a series of U fibers that course beneath the cortical mantle to connect adjacent regions in striate, prestriate, and inferior temporal cortex. We suggest that the occipital and temporal lobes in human beings are similarly connected by a series of U fibers and that the term inferior longitudinal fasciculus be replaced with the term occipitotemporal projection system. Different clinical syndromes attributed to lesions of the inferior longitudinal fasciculus, including visual agnosia, prosopagnosia, and impaired visual recent memory, are probably due to interruption of fibers at different points along this projection system.

Animals↗

Comment on the use of self-reporting instruments to assess patients with rheumatoid arthritis: the longitudinal association between the DAS28 and the VAS general health.

OBJECTIVE: Recently, the use of patient self-reporting instruments instead of clinical, objective measurements to assess rheumatoid arthritis (RA) patients was proposed. This assumes a constant association between disease activity and the self-reporting instruments. The objective was to explore the association (in time) between disease activity and patient perception of general health, disease activity, pain, and functional disability in patients with RA. METHODS: Data of 624 newly diagnosed RA patients who completed 3 years of followup were analyzed. Cross-sectional linear regression models and longitudinal regression models were estimated, with a visual analog scale (VAS) measuring general health (VAS-GH; 0 = best, 100 = worst) as a dependent variable and the Disease Activity Score (DAS28) without the VAS-GH as an independent variable. Other dependent variables were VAS disease activity, pain, and the Health Assessment Questionnaire. RESULTS: The DAS28 and VAS-GH were significantly associated in RA patients (P < 0.001). However, the explained variance was low (6.7%). From diagnosis to 3 years after the diagnosis, the intercept decreased given the same regression coefficient. The longitudinal regression model showed that the VAS-GH improved during disease course independent of a change in DAS28. Analyses on the other outcome parameters showed similar results. CONCLUSION: Patients' perception of health can be different with equal disease activity, depending on the moment in the disease course. Furthermore, our results indicate that self-reported measures on functionality, disease activity, and general health cannot substitute for objective measures of disease activity in RA in longitudinal studies; subsequently, both need to be measured.

Adult↗

Imaging longitudinal cardiac strain on short-axis images using strain-encoded MRI.

This article presents a new method for measuring longitudinal strain in a short-axis section of the heart using harmonic phase magnetic resonance imaging (HARP-MRI). The heart is tagged using 1-1 SPAMM at end-diastole with tag surfaces parallel to a short-axis imaging plane. Two or more images are acquired such that the images have different phase encodings in a direction orthogonal to the image plane. A dense map of the longitudinal strain can be computed from these images using a simple, fast computation. Simulations are conducted to study the effect of noise and the choice of out-of-plane phase encoding values. Longitudinal strains acquired from a normal human male are shown.

Adult↗

Evolution of the longitudinal magnetization for pulse sequences using a fast spin-echo readout: application to fluid-attenuated inversion-recovery and double inversion-recovery sequences.

The fast spin-echo (FSE) sequence is frequently used as a fast data-readout technique in conjunction with other pulse sequence elements, such as in fluid-attenuated inversion-recovery (FLAIR) and double inversion-recovery (DIR) sequences. In order to implement those pulse sequences, an understanding is required of how the longitudinal magnetization evolves during the FSE part of the sequence. This evolution has been addressed to a certain extent by previous publications, but the DIR literature in particular appears to be replete with approximations to the exact expression for the longitudinal magnetization, and several papers contain errors. Equations are therefore presented here for the evolution of the longitudinal magnetization for a FSE readout. These are then applied to calculate the magnetization available immediately prior to the 90 degrees imaging pulse for the FLAIR-FSE and DIR-FSE pulse sequences.

Animals↗

Effects of Jaoga-Yukmiwon(R), a Korean herbal medicine, on chondrocyte proliferation and longitudinal bone growth in adolescent male rats.

Externally visible growth of the body is the result of proliferation of chondrocytes and longitudinal bone growth. The effects of the Korean herbal medicine, Jaoga-Yukmiwon((R)), on the growth of adolescent rats were investigated in the present study. The proliferation ratio of chondrocytes was calculated from 5-bromo-2'-deoxyuridine incorporation during DNA synthesis. The 5-bromo-2'-deoxyuridine incorporation ratio of the control group was 21.1 +/- 3.5%, and Jaoga-Yukmiwon((R)) administration markedly increased the ratio to 34.5 +/- 4.6% (p < 0.05). The bone formation rate of longitudinal bone was estimated by labelling with tetracycline, which binds to newly formed bone. The bone formation rate in the tibia of Jaoga-Yukmiwon((R))-administered rats was increased to 405.1 +/- 4.3 micro m (p < 0.05) from 292.2 +/- 11.8 micrometer (control value). The height of the growth plate in the administrated rats was increased to 614.6 +/- 10.0 micro m (p < 0.05) from 552.3 +/- 17.1 micro m. The bone morphogenetic protein-2 immunostaining in the growth plate was also increased. These results suggest that Jaoga-Yukmiwon((R)) may promote longitudinal bone growth during the developmental period.

Animals↗

Quantitative measurement of longitudinal and transverse cross-relaxation rates: an application to the analysis of the internal dynamics of ranalexin in water and trifluoroethanol.

We describe a quantitative processing method which gives access to the longitudinal and transverse cross-relaxation rates from off-resonance ROESY intensities. This method takes advantage of the dependence of the off-resonance ROESY experiments at any mixing time and any spin-lock angle &theta; on two relaxation matrices, the longitudinal and the transverse ones. This allows one to take into account multistep magnetization transfers even if the measurements are performed only at one or two mixing times. The ratio of the longitudinal to transverse cross-relaxation rates can then be used as a local indicator of the internal dynamics, without assuming a structure or a model of motion. After validation of this processing method by numerical simulations, it is applied to the analysis of the dynamics of the peptide ranalexin dissolved in pure water and in water/TFE.

Anti-Infective Agents↗

An iterative fitting procedure for the determination of longitudinal NMR cross-correlation rates.

We present a method to measure (15)N-(1)H dipolar/(15)N CSA longitudinal cross-correlation rates in protonated proteins. The method depends on the measurement of four observables: the cumulative proton-proton cross relaxation rates, the (15)N R(1) relaxation rate, the multiexponential decay of 2N(Z)H(N)(Z) spin-order, and multiexponential buildup of 2N(Z)H(N)(Z) spin-order. The (15)N-(1)H dipolar/(15)N CSA longitudinal cross-correlation rate is extracted from these measurements by an iterative fitting procedure to the solution of differential equations describing the coupled relaxation dynamics of the z-magnetization of the (15)N nucleus, the two-spin-order 2N(Z)H(N)(Z), and a two-spin-order term 2N(Z)H(Q)(Z) describing the interaction with remote protons. The method is applied to the microbial ribonuclease binase. The method can also extract longitudinal cross-correlation rates for those amide protons that are involved in rapid solvent exchange. The experiment that serves for extracting proton-proton cross-relaxation rates is a modification of 3D (15)N-resolved NOESY-HSQC. The experiment restores the solvent magnetization to its equilibrium state during data detection for all phase cycling steps and all values of NOE mixing times and is recommended for use in standard applications as well.

Hydrogen↗

Cross correlations in the longitudinal relaxation of strongly coupled spins

A generalized set of magnetization modes for quantifying cross-correlation contributions to longitudinal relaxation in strongly coupled spin systems is described in this paper. Such a set of modes (called longitudinal multiple-quantum modes) is used to unravel cross-correlation information in strongly coupled systems, where the strength of the J coupling tends to obscure such effects. The applicability of such methods is demonstrated for a small molecule which exhibits some strong coupling effects even at high magnetic field strengths. The contribution of "remote" cross correlations to the longitudinal relaxation of strongly coupled spins is detailed. Copyright 2000 Academic Press.

Journal Article↗

Longitudinally detected EPR: improved instrumentation and new pulse schemes.

A new setup for longitudinal detection (LOD) of EPR signals based on a commercial pulse EPR spectrometer equipped with an ENDOR probehead is presented. The design is suited for pulse LOD EPR and amplitude-modulated cw LOD EPR experiments. The sensitivity is substantially increased compared with earlier designs. Two new pulse schemes that take full advantage of the special properties of the setup are invented. In transient-nutation longitudinally detected EPR (TN-LOD EPR), the nutation of magnetization during a microwave pulse is used to measure the EPR signal. In pulse-train excited longitudinally detected EPR (PT-LOD EPR), a train of microwave pulses that periodically inverts the magnetization is applied. First experimental results on radicals and metal complexes at room temperature are presented.

Journal Article↗

Microcirculatory perfusion of the canine esophagus before and after blind longitudinal dissection and thoracoscopic distal transsection.

In the treatment of distal esophageal pathology, surgical mobilization and exteriorization of the thoracic esophagus can be necessary. This may threaten its vascularization. We investigated the effect of longitudinal dissection and distal transsection on the microcirculatory perfusion of the canine esophagus. Esophageal perfusion and muscular oxygenation were investigated in 11 dogs using laser Doppler fluxmetry and oxygen pressure measurements before and up to 2 weeks after longitudinal dissection with and without distal thoracoscopic transsection. Histological examination was performed at the end of the follow-up period. Distal esophageal perfusion was higher than proximal. Longitudinal dissection caused an insignificant reduction, whereas additional transsection significantly lowered esophageal perfusion, which was restored only partially during follow-up. After transsection distal muscular oxygen pressure was also significantly lower than proximal. Histologically, no significant ischemic cell damage was observed. Laser Doppler perfusion measurement is a feasible technique to measure (changes in) microcirculatory circulation of the esophageal wall. This may be useful in clinical settings to monitor the viability of the esophagus after surgical interventions. Distal transsection substantially reduces esophageal perfusion without apparent short-term histological damage.

Animals↗

Inhibition of the contraction of the isolated longitudinal muscle of the guinea-pig ileum by botulinum C2 toxin: evidence for a role of G/F-actin transition in smooth muscle contraction.

The effect of botulinum C2 toxin was studied on the contractions of the guinea pig ileum myenteric plexus longitudinal muscle preparation. Botulinum C2 toxin inhibited the muscle contraction induced by electrical stimulation (60 V; 0.5 ms; 0.33 Hz) in a time and concentration dependent manner. The inhibitory effect occurred with a time lag of about 1 h, and depended on the presence of both toxin components. After 4 h of incubation with 1.7 micrograms/ml of component I and 6.7 micrograms/ml of component II of botulinum C2 toxin, the smooth muscle contraction was inhibited by about 60%. At these toxin concentrations, about 55% of the modifiable smooth muscle actin was ADP-ribosylated. Smooth muscle contraction induced by bradykinin and bethanechol were similarly inhibited. Moreover, the C2 toxin inhibited muscle contraction induced by Ba2+, and by direct muscle membrane depolarization (60 V; 10 ms; 0.33 Hz) after suppression of acetylcholine release by normorphine. Also cytochalasin D inhibited the electrically evoked contraction of the ileum longitudinal muscle. In contrast to botulinum C2 toxin, inhibition of contractility by cytochalasin D occurred without a lag phase, and was reversed by washing off the toxin. In contrast of guinea pig ileum longitudinal muscle, botulinum C2 toxin did not reduce the contraction of the rabbit aortic smooth muscle stimulated by K+-depolarization or noradrenaline.

Actins↗