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PubMed2006

Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa.

BACKGROUND: Highly active antiretroviral therapy (HAART) can improve cognitive performance in some patients with HIV-associated cognitive impairment in the United States. The effect of HAART on HIV dementia in sub-Saharan Africa is largely unknown. OBJECTIVE: To evaluate neuropsychological test and functional performance in HIV+ individuals after 3 and 6 months of HAART in Uganda. METHODS: Twenty-three HIV+ individuals receiving HAART also received a detailed clinical history, neuropsychological testing, and a functional assessment. Follow-up evaluations were performed at 3 and 6 months after baseline. Longitudinal changes in the HIV dementia stage, the mean Z score for each neuropsychological test, and the Karnofsky Functional Performance Scale were evaluated at 3 and 6 months. RESULTS: The mean (SD) CD4 cell count improved from 71 (15) at baseline to 161 (30) at 3 months (p = 0.005) and 222 (46) at 6 months (p < 0.001). Improvements were found in the Memorial Sloan Kettering HIV dementia stage and in tests of verbal memory, psychomotor speed, and executive functioning after 3 and 6 months of HAART (p < 0.001 at 6 months for each neuropsychological test). There was also improvement in the Karnofsky Functional Performance Scale at both 3 and 6 months after the initiation of HAART (p < 0.001). CONCLUSION: Highly active antiretroviral therapy (HAART) can be associated with improvement in neurocognitive and functional performance in HIV+ individuals in sub-Saharan Africa. These results suggest that HAART, if available in areas with limited resources in sub-Saharan Africa, should be provided for patients with HIV-associated cognitive impairment.

Adult↗
PubMed1988

Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration.

To explore the nature of the olfactory dysfunction associated with Parkinson's disease (PD), 81 PD patients who scored well on a cognitive screening test were administered the 40-odorant University of Pennsylvania Smell Identification Test; 38 were additionally given a forced-choice phenylethyl alcohol odor detection threshold test. Clinical ratings of 11 neurologic symptoms (three bilateral) were obtained at the time of testing, and odor identification was retested in 24 patients at intervals ranging from 5 to 39 months. Relative to matched controls, the PD patients exhibited consistent and marked decrements on both types of olfactory tests (ps less than 0.0001). The odor identification deficit was not restricted to any subset of odorants and did not evidence longitudinal change. A factor analysis of the intercorrelations among the variables yielded six easily interpretable factors: general motor, oral motor, olfactory function, cognitive function, tremor, and gender. Olfactory test scores were independent of all other measures, including disease stage and duration. Seventy-two percent of the PD patients were unaware of a smell disorder before testing; those who were aware had significantly lower test scores. A statistical comparison of PD patients' olfactory test scores to those obtained from Alzheimer's disease patients found the olfactory disorders of these diseases to be indistinguishable. The data support the hypothesis that the olfactory deficit of PD is a general and stable one which likely occurs early in the disease process.

Aged↗
PubMed1996

Hippocampal formation size predicts declining memory performance in normal aging.

Hippocampal formation (HF) atrophy, although common in normal aging, has unknown clinical consequences. We used MRI to derive HF size measurements at baseline on 44 cognitively normal older adults entering a longitudinal study of memory function (mean age = 68.4 years, mean follow-up = 3.8 years). Only one subject became demented at follow-up. Multiple regression analyses controlling for age, gender, education, and diffuse cerebral atrophy revealed that HF size significantly predicted longitudinal change on memory tests previously found sensitive to decline in normal aging. These results indicate HF atrophy may be a risk factor for accelerated memory dysfunction in normal aging.

Aged↗
PubMed2001

Prevalence and correlates of parkinsonism in patients with primary depression.

The authors examined the prevalence, clinical correlates, and longitudinal changes of parkinsonism in 94 patients with primary depression and 20 healthy control subjects. Parkinsonism was present in 20% of patients with primary depression. This syndrome was significantly associated with older age, more severe depression, and more severe cognitive impairment. In a subgroup of depressed patients, parkinsonism was reversible upon recovery from the mood disorder.

Aged↗
PubMed2001

Clinical markers of early disease in persons near onset of Huntington's disease.

OBJECTIVE: There is increasing evidence that neuron loss precedes the phenotypic expression of Huntington's disease (HD). As genes for late-onset neurodegenerative diseases are identified, the need for accurate assessment of phenoconversion (i.e., the transition from health to the disease phenotype) will be important. METHODS: Prospective longitudinal evaluation using the Unified Huntington's Disease Rating Scale (UHDRS) was conducted by Huntington Study Group members from 36 sites. There were 260 persons considered "at risk" for HD who initially did not have manifest disease and had at least one subsequent evaluation. Repeat UHDRS data, obtained an average of 2 years later, showed that 70 persons were given a diagnosis of definite HD based on the quantified neurologic examination. RESULTS: Baseline cognitive performances were consistently worse for the at-risk group who demonstrated conversion to a definitive diagnosis compared with those who did not. Longitudinal change scores showed that the at-risk group who did not demonstrate manifest disease during the follow-up study period demonstrated improvements in all cognitive tests, whereas performances in the at-risk group demonstrating conversion to disease during the study declined across cognitive domains. CONCLUSIONS: Neuropsychological measures show impairment 2 years before the development of more manifest motor disease. Findings suggest that these brief cognitive measures administered over time may capture early striatal neural loss in HD.

Adult↗
PubMed1992

Standardized lateral oblique projection of the mandible for digital subtraction radiography.

A special apparatus was developed for standardization of the lateral oblique projection of the mandible (LOPM) in order to apply the digital subtraction method. Geometric reproducibility was examined over an 8-week period using a dry skull. Angulation errors were determined by the relation to image noise in the subtraction image. It was found that the relation between image noise and angulation error was approximated by a second-order polynomial. Geometric reproducibility was within 1 degree over the experimental period. These results suggest that this standardized LOPM is satisfactory for clinical application of digital subtraction. Two cases are presented where this technique was used to demonstrate longitudinal changes in bone density.

Adult↗
PubMed2004

Geometric alignment and chromatic calibration of serial radiographic images.

OBJECTIVE: To develop software for automated registration and intensity calibration of serial dental radiographs for the analysis of longitudinal changes in bone density. METHODS: Serial dental radiographs were acquired using a positioning device designed to minimize projection divergence. Each radiograph included an image of a standardized aluminium wedge. The radiographs were scanned on a flatbed scanner (AGFA Duo Scan) with a spatial resolution of 300 dpi, and pixel intensity coded in 16-bit grey scale. The intensity was calibrated using serial images of selected areas with defined thickness of the aluminium wedge. A robust B-splines multiresolution registration algorithm was implemented to overcome the acquisition misalignment. Radiographs, taken before and after periodontal therapy, were subtracted to assess bone density evolution. RESULTS: The intensity calibration decreased the maximum intensity variations between serial radiographs from 30+/-17% to 1+/-1% (mean+/-standard deviation), and improved the visual comparison between the radiographs. The registration stage allowed correcting the misalignment of the radiographs on the scanner screen and superimposing the radiography contents. The observed residual motion was about 0.02+/-0.01 mm. CONCLUSION: Very user-friendly software was developed. The manipulator needs to scan the radiographs only one time. The software performs all subsequent processing steps.

Absorptiometry, Photon↗
PubMedDate not supplied

Lipid profile during pregnancy in HIV-infected women.

PURPOSE: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. METHOD: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (PIs) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. RESULTS: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p < .001), 60.8 mg/dL for total cholesterol (p < .001), 13.7 mg/dL for HDL cholesterol (p < .001), and 17.8 mg/dL for LDL cholesterol (p = .001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on PIs. The effect of PIs on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. CONCLUSION: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV.

Adult↗
PubMed2000

Optimal scaling of a longitudinal choice variable with time-varying representation of individuals.

A new method of homogeneity analysis is proposed for analysing the repeated measurements of n individuals' choices among m categories. In this method, time-varying scores are assigned to each individual, while time-invariant ones are assigned to each category. For obtaining such scores, a requirement of homogeneity for time-varying individual scores is introduced in addition to the individual-category homogeneity requirement underlying the existing homogeneity analysis. The loss function based on these two requirements is minimized under a suitable normalization condition. This minimization is explicitly attained through eigen-value decomposition, and the graphical representation of the resulting scores allows us to easily find the longitudinal changes in individuals and the relationships among categories.

Choice Behavior↗
PubMed1997

High-impact exercise promotes bone gain in well-trained female athletes.

Maximizing peak bone mass, as well as reducing its loss after menopause, is important for the prevention of osteoporosis. One mode of activity, gymnastics training, invokes high impact loading strains on the skeleton which may have powerful osteogenic effects. To examine the role of athletic activity, specifically gymnastics, on bone mineral density (BMD) accretion, we monitored longitudinal changes in regional and whole body BMD in collegiate women gymnasts and competitive athletes whose skeletons are exposed to differential loading patterns: runners and swimmers. Two cohorts were studied. Cohort I = 26 gymnasts (19.7 +/- 1.2 years), 36 runners (21.1 +/- 2.7 years) and 14 nonathletic women (19.3 +/- 1.7 years) followed over an 8-month period. Cohort II = 8 gymnasts (18.9 +/- 1.1 years), 11 swimmers (20.0 +/- 2.3 years) and 11 nonathletic women (19.0 +/- 1.2 years) followed over a 12-month period. Lumbar spine (L2-4), femoral neck, and whole body BMD (g/cm2) were assessed by dual-energy X-ray absorptiometry. For cohort I, the percent change in lumbar spine BMD after 8 months was significantly greater (p = 0.0001) in the gymnasts (2.8 +/- 2.4%) than in the runners (-0.2 +/- 2.0%) or controls (0.7 +/- 1.3%). An increase in femoral neck BMD of 1.6 +/- 3.6% in gymnasts was also greater (p < 0.05) than runners (-1.2 +/- 3.0%) and approached significance compared with controls (-0.9 +/- 2.2%, p = 0.06). For cohort II, gymnasts gained 2.3 +/- 1.6% at the lumbar spine which differed significantly (p < 0.01) from changes in swimmers (-0.3 +/- 1.5%) and controls (-0.4 +/- 1.7%). Similarly, the change at the femoral neck was greater (p < 0.001) in gymnasts (5.0 +/- 3.4%) than swimmers (-0.6 +/- 2.8%) or controls (2.0 +/- 2.3%). The percent change in BMD at any site did not differ between eumenorrheic and irregularly menstruating athletes. These results indicate that bone mineral at clinically relevant sites, the lumbar spine and femoral neck, can respond dramatically to mechanical loading characteristic of gymnastics training in college-aged women. This occurred despite high initial BMD values and was independent of reproductive hormone status. The results provide evidence to support the view that high impact loading, rather than selection bias, underlies high BMD values characteristic of women gymnasts. Because all athletes underwent resistance training throughout the year of study, muscle strengthening activity did not appear to be a significant factor in the skeletal response observed in gymnasts. We conclude that activities resulting in high skeletal impacts may be particularly osteotropic for young women.

Absorptiometry, Photon↗
PubMed2004

Lung function decline in cystic fibrosis patients and timing for lung transplantation referral.

STUDY OBJECTIVES: To determine risk factors associated with an accelerated decline in lung function in cystic fibrosis (CF), and whether longitudinal changes in FEV(1) would be a better predictor of the need for referral for lung transplantation than any single value for FEV(1.) DESIGN: The rate of decline in pulmonary function was determined by standard linear regression from each patient's calendar year's best percentage of predicted FEV(1) (%FEV(1)) over at least 4 years, and patients were classified into three cohorts based on their rate of decline. Differences between groups in age, weight-for-age z score, gender, genotype, pancreatic status, diabetes, and the presence of various lung microbial isolates were analyzed. A subset of 30 patients referred for lung transplantation were further analyzed, and a prediction model for lung transplantation referral was created using the patient's rate of decline in lung function, the mean waiting time for donor organs, and the average level of lung function of patients prior to lung transplantation. PATIENTS: One hundred fifty-three patients with CF followed up at the Washington University Adult Cystic Fibrosis Center. RESULTS: Younger age, malnutrition, and concurrent infection with both Pseudomonas aeruginosa and Staphylococcus aureus were significant (p < 0.05) risk factors for rapidly declining lung function. Among patients with rapidly declining lung function, referral for lung transplantation would have occurred 8.4 months earlier than actual referral age (p < 0.05) if the prediction model had been used, possibly resulting in additional patient salvage in several cases. CONCLUSIONS: Rate of decline in lung function should be routinely evaluated in patients with CF, and a prediction model utilizing the rate of decline in %FEV(1), and the median regional waiting period for donor lungs for patients with CF may assist in the timing of referral for lung transplantation and more rapidly declining lung function.

Adult↗
PubMed2000

Familial studies on the genetics of cardiovascular diseases: the Stanislas cohort.

In a given individual, the level of cardiovascular risk results from the combination of and interactions between genetic and environmental components. We choose to investigate segregation analysis of intermediate phenotypes in healthy nuclear families, belonging to the Stanislas cohort, a large familial cohort composed of 1006 families, which will be followed for 10 years. We developed a panel of 35 genetic markers including genes involved in lipid metabolism, regulation of blood pressure, thrombosis, platelet function, and endothelial cell adhesion. The allele frequencies of the studied polymorphisms were in agreement with those reported in other Caucasian populations. As an example of segregation analysis, we investigated carotid intima-media thickness (CIMT) variability in a subset sample of the Stanislas cohort. We found that about 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in apo CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase, and fibrinogen genes were observed and explained about 20% of CIMT variability in men. Furthermore, as another example of association studies, we investigated the relations between E-selectin polymorphisms and blood pressure interindividual variability and longitudinal changes in unrelated adults of this familial population. The E-selectin Phe554 allele was found associated with lower systolic blood pressure and diastolic blood pressure.

Adult↗
PubMed2006

Transient neonatal hyperparathyroidism: a presenting feature of mucolipidosis type II.

The phenotype of mucolipidosis type II (ML II), a disorder of lysosomal enzyme transport, includes mucopolysaccharidosis type I (Hurler syndrome)-like features and dysostosis multiplex, usually apparent after 6 months of age. We describe here the natural history of neonatal hyperparathyroidism, a recently described presentation of ML II. A female neonate presented with multiple fractures and radiological features of osteopenia and 'rickets-like' changes. Longitudinal evaluation, while the patient was treated with vitamin D 800-3,000 IU/day orally, indicated secondary hyperparathyroidism which resolved, biochemically and radiologically, by age 4 months. Neonatal hyperparathyroidism in ML II is severe, transient, and probably secondary to impaired placental calcium transport, simulating a condition observed in the offspring of chronically hypocalcemic mothers.

Bone Diseases, Metabolic↗
PubMed1975

Alcohol consumption and personal resources. A general hypothesis and some implications.

A general hypothesis is formulated in which alcohol consumption is largely determined by the resources available for drinking, the activities competing for those resources, and the costs associated with drinking in the context of a particular social status. Implications in terms of drinking patterns of occupational subgroups, longitudinal changes in alcohol consumption, and vulnerability to the development of pathological drinking are suggested.

Age Factors↗
PubMed1985

Post-natal thyroid function in low birth weight infants; a longitudinal assessment of free thyroxine and thyroid hormone binding globulin.

Because the concentrations of serum free thyroxine (FT4) and thyroid hormone binding globulin (TBG) have not been fully evaluated in preterm infants at the immediate post-natal period, we studied the longitudinal changes of serum FT4 and TBG, along with thyroxine (T4) and thyroid stimulating hormone (TSH), at birth (cord blood), 2 days, 1 week and 2 weeks of age in 7 infants with birth body weight less than or equal to 1000 g, 7 infants with body weight 1001 to 1350 g, 11 infants with body weight 1351 to 2499 g, and 11 full-term infants. Free T4 concentrations were measured by Corning Medical radioimmunoassay (RIA) kit. The infants with extremely low birth weight (ELBW) (body weight less than or equal to 1000 g) showed precipitous declines of total T4 and, to a lesser extent, of FT4 concentrations at 1 and 2 weeks of age. These post-natal T4 and FT4 decreases in ELBW neonates have not previously been reported. The clinical significance of this finding remains, speculative, but it may be due to metabolic or nutritional problems related to extreme prematurity itself. This study suggests that measurement of FT4 is a useful adjunct to the assessment of ELBW infants with very low T4 values, if done between 1 to 2 weeks of age, and could be used as a primary hypothyroid screening tool instead of T4 measurements, provided that an FT4 assay is developed that uses the elute of blood spotted on filter paper.

Age Factors↗
PubMed2003

Pathophysiology and functional consequences of human partial epilepsy: lessons from positron emission tomography studies.

Positron emission tomography (PET) is a powerful clinical and research tool that, in the past two decades, has provided a great amount of novel data on the pathophysiology and functional consequences of human epilepsy. PET studies revealed cortical and subcortical brain dysfunction of a widespread brain circuitry, providing an unprecedented insight in the complex functional abnormalities of the epileptic brain. Correlation of metabolic and neuroreceptor PET abnormalities with electroclinical variables helped identify parts of this circuitry, some of which are directly related to primary epileptogenesis, while others, adjacent to or remote from the primary epileptic focus, may be secondary to longstanding epilepsy. PET studies have also provided detailed data on the functional anatomy of cognitive and behavioral abnormalities associated with epilepsy. PET, along with other neuroimaging modalities, can measure longitudinal changes in brain function attributed to chronic seizures as well as therapeutic interventions. This review demonstrates how development of more specific PET tracers and application of multimodality imaging by combining structural and functional neuroimaging with electrophysiological data can further improve our understanding of human partial epilepsy, and helps more effective application of PET in presurgical evaluation of patients with intractable seizures.

Epilepsies, Partial↗
PubMed2002

Species composition and spatial distribution of a stream fish assemblage in the east coast of Brazil: comparison of two field study methodologies.

The species composition and spatial distribution of a fish assemblage were studied in three reaches of a river in the east coast of Brazil: a section of rapids (upper), another of water flowing on plain terrain (lowland) and the other of a mangrove environment. Two methods were employed with the purpose of estimating their effectiveness in naturalistic studies of tropical fish assemblages. One method consisted of underwater observations and the other was characterized by catches using gears such as fish traps, sieves and fishing rods. Both methods showed that their effectiveness is dependent upon the characteristics of the environment and the biology of the species. In areas of high water transparency and flow speed rocky substrate and no submerged marginal vegetation (upper reach), the employment of the traditional gears was quite inefficient, despite the excellent conditions for underwater observations. In areas of clear water and high flow speed with abundant submerged marginal vegetation (lowland and mangrove), the gears were rather efficient yielding excellent results when coupled with direct observation methods. Since the abiotic characteristics of a stream change longitudinally, it is appropriate to employ different methods in the study of the ichthyofauna composition and distribution in order to reduce the constraints imposed by sampling methods in running waters.

Analysis of Variance↗
PubMed2005

Imaging of multiple sclerosis: role in neurotherapeutics.

Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normal-appearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

Animals↗