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Placebo therapy for postmenopausal osteoporosis.

Eighteen postmenopausal osteoporotic (PMO) women on placebo therapy were followed for 1 year. Serial measurements of calcium balance and kinetics, bone histomorphometry, photon absorptiometry, and radiogrammetry were obtained. Few significant changes in balance and kinetics or bone histology were seen in these women over time. Photon absorptiometry and radiogrammetry of the femoral cortex showed a significant annual bone loss however. When compared with premenopausal and healthy postmenopausal women, the annual bone loss in those with PMO was significantly greater. The ability of balance studies, photon absorptiometry, and radiogrammetry to predict the magnitude of this bone loss was similar. Finally, there was an illustration of the use of the estimated variance provided by this study for estimating sample size for future studies.

Aged↗

Proprioception, kinesthesia, and balance after total knee arthroplasty with cruciate-retaining and posterior stabilized prostheses.

BACKGROUND: The effect of total knee arthroplasty on proprioception, kinesthesia, and postural control remains controversial. It is argued that retaining the posterior cruciate ligament may help to preserve these sensorimotor functions and improve the longevity of the prosthesis and the functional outcome. We performed a prospective, randomized study to assess proprioception, kinesthesia, and balance following total knee arthroplasty with cruciate-retaining and posterior stabilized prostheses. METHODS: Twenty patients scheduled to undergo total knee arthroplasty were randomly assigned to receive either a cruciate-retaining or a posterior stabilized prosthesis. Joint-position sense, the threshold to detect joint motion, and the subject's ability to balance on an unstable platform were assessed prior to and at least six months after the operation. Paired two-tailed t tests (with a level of significance of p < 0.05) were used to assess the effect of the arthroplasty on the preoperative measures for all subjects. Analysis of covariance was performed to identify the effects of prosthetic design. RESULTS: Following total knee arthroplasty, patients detected motion significantly faster and reproduced joint position with less error. The balance index also improved significantly from the preoperative to the postoperative evaluation. The group treated with the posterior stabilized prosthesis more accurately reproduced joint position when the knee was extended from a flexed position. CONCLUSIONS: Total knee arthroplasty results in mild improvements in proprioception, kinesthesia, and balance. These changes may result from the retensioned capsuloligamentous structures and reduced pain and inflammation. Retention of the posterior cruciate ligament does not appear to significantly improve proprioception and balance compared with those functions in patients with a posterior stabilized total knee design.

Aged↗

A self-referent thinking model: how older adults may talk themselves out of being physically active.

The purpose of this qualitative study was to ground current theory on exercise behavior with authentic voices of older adults as they thought about physical activity. Aged 55 to 92, 41 adults of various activity levels provided interviews with regard to personal experiences, health issues, and motivation for active lifestyles. Key constructs from four contemporary health behaviour theories were integrated into a decisional balance template. Interpretive analysis organized positive and negative thinking on the template and thereby animated important theoretical constructs with the actual voices of older adults. Although generally supporting current theoretical models, the surprising finding was that active people expressed as much negative self-talk as did inactive people. However, they differed in their ability to balance each issue with strong positive thinking based on previous personal succesess and direct experience of benefits. This finding suggests that promoting health through lifestyle change is very difficult to do without positive past-mastery experiences.

Aged↗

Age-related differences in muscle power during single-step balance recovery.

The purpose of this study was to investigate age-related differences in muscle power during a surrogate task of trip recovery. Participants included 10 healthy young men (19-23 years old) and 10 healthy older men (65-83). The task involved releasing participants from a forward-leaning posture. After release, participants attempted to recover their balance using a single step of the right foot. Muscle power at the hip, knee, and ankle of the stepping limb were determined from the product of joint angular velocity and joint torque. Muscle powers during balance recovery followed a relatively consistent pattern in both young and older men, and showed effects of both lean and age. Interestingly, the effects of age did not always involve smaller peak power values in the older men as expected from the well-documented loss of muscle power with aging. Older men exhibited smaller peak muscle power at the knee and larger peak muscle power at the ankle and hip compared to young men. The increases in muscle power at the ankle and hip may result from a neuromuscular adaptation aimed at improving balance recovery ability by compensating for the age-related loss of muscle function.

Adult↗

Frontal lobe dysfunction in pathological gambling patients.

BACKGROUND: Limited data are available about the validity of the diagnosis of pathological gambling (PG) and about the etiology and the efficacy of different treatment strategies of this disorder; however, similarities in decision-making behavior between PG patients and patients with ventromedial prefrontal cortex lesions suggest a possible implication of these areas in the pathophysiology of this disorder, as in obsessive-compulsive disorder, in which the decision-making impairment is significantly associated with response to serotonin reuptake inhibitor treatment. Nevertheless, several studies have shown that decision-making functioning is also impaired in drug-addicted patients who have shown abnormalities in ventromedial prefrontal cortex during functional neuroimaging studies. METHODS: We assessed the decision-making function mediated by the ventromedial prefrontal cortex in 20 PG patients and 40 healthy control (HC) subjects using the Gambling Task, which simulates real-life decision-making, testing the ability to balance immediate rewards against long-term negative consequence. RESULTS: Significant differences were found in Gambling Task performance between HC subjects and PG patients, who showed a specific decision-making profile across the sequence of the game. The dissimilarity does not appear to depend on the basic cognitive function deficit of the PG group. CONCLUSIONS: These data seem to suggest the existence of a link between PG and other disorders (i.e., obsessive-compulsive disorder and drug addiction) all having diminished ability to evaluate future consequences, which may be explained at least in part by an abnormal functioning of the orbitofrontal cortex.

Adult↗

Judo, better than dance, develops sensorimotor adaptabilities involved in balance control.

OBJECTIVES: Training allows sportsmen to acquire new balance control abilities, possibly differing according to the discipline practised. We compared, by means of static and dynamic posturographic tests, the postural skills of high-level judoists, professional dancers and controls, in order to determine whether these sports improved postural control. RESULTS: With eyes open, judoists and dancers performed better than controls, indicating a positive effect of training on sensorimotor adaptabilities. Yet, with eyes closed, only judoists retained a significantly better stance. CONCLUSIONS: These data indicate that the practice of a high-skill activity involving proprioceptive afferences especially improves both performance and balance control.

Adult↗

The prevention of falls in later life. A report of the Kellogg International Work Group on the Prevention of Falls by the Elderly.

Although falls among the elderly carry high costs to individuals and society, the prevention of falls in later life has not received adequate attention from health care professionals. The prevalence of falls appears to involve roughly one-third of persons aged 65 and over, and the risk of falling and suffering serious injury increases substantially up to the eighth decade of life. The proportion of falls which result in fracture is low, but the absolute number of older people who suffer fractures is high and places heavy demands on health care systems. Even falls which result in no physical injury often have serious social and psychological consequences for the elderly, including loss of confidence and restrictions in mobility, and high proportions of older people report fears of falling. There is a need to provide accurate information about the causes and prevention of falls in later life. Falls are not part of the normal aging process. Rather, they are due to underlying physical illnesses, medications, and environmental hazards, often in interaction. This report provides an overview of the elderly population at risk of falling and suffering serious injury, some of the reasons older people fall, and the methods to prevent falls which have been developed in both community and institutional settings. In addition, it suggests some of the practical steps which can be taken by health and social care professionals and by older people and their families in order to prevent falls. Empirical knowledge about the causes of falls by the elderly and the most effective methods of prevention remains limited. Major barriers to research have been the lack of a clear definition of a fall and the fact that falls are not included in medical diagnostic indices. It is recommended that falls be recorded as a disease entity in Index Medicus and in the International Classification of Diseases Xth Revision. To facilitate future comparisons of research findings on falls, a definition of a fall is proposed. The report underscores that the causes of falls are very different for persons of varying ages, health status, and levels of mobility. While the many risk factors for falls are not yet known, poor health status, especially chronic illness, impaired mobility and postural instability, and a history of prior falls have been associated with the risk of falling. Balance, the ability to prevent falls upon displacement, can be impaired by disease or age-related changes in a number of anatomical structures, by medications which reduce their efficient functioning, and by environmental hazards.(ABSTRACT TRUNCATED AT 400 WORDS)

Accident Prevention↗

Effects of polyethylene glycol on water and saline intake in the Mongolian gerbil.

To establish the water balance regulatory ability of gerbils in response to a hypovolemic dipsogen, adult female gerbils (50-70 g) were injected subcutaneously with either a .9% NaCl vehicle or 10% or 30% (wt/vol) polyethylene glycol (mol wt 20,000). At each injection level one-half of the Ss had access to water, the other to .9% NaCl after injection. There was a significant increase in fluid intake associated with injection doses and Ss drank significantly more when allowed saline to drink rather than water. In Experiment II under a similar set of manipulations, hematocrit values were obtained at 12 and 24 hours after injection and showed decreasing blood volume levels which apparently served as the thirst stimulus. The results were discussed in terms of the voluntary dehydration findings of Stricker on rats and thus demonstrated the similarity of gerbils and rats in response to extracellular insult.

Animals↗

Differing risk factors for falls in nursing home and intermediate-care residents who can and cannot stand unaided.

OBJECTIVES: To determine fall risk factors in nursing home and intermediate-care residents who can and cannot stand unaided. DESIGN: Prospective cohort study. SETTING: Residential elderly care facilities in Sydney, Australia. PARTICIPANTS: One thousand people aged 65 to 103 (mean age +/- standard deviation: 85.0 +/- 7.4). MEASUREMENTS: Accidental falls. RESULTS: Fall rates were highest in those with fair standing balance, intermediate in those with the best standing balance, and lowest in those with the worst standing balance. This nonlinear pattern was even more striking when subjects were categorized according to their standing balance and ability to rise from a chair. Using this dual classification, fall rates were highest in those who could rise from a chair but could not stand unaided (81%) and lowest in those who could neither rise from a chair nor stand unaided (48%). In residents who could stand unaided, risk factors included increased age, male sex, higher care classifications, incontinence, psychoactive medication use, previous falls, and slow reaction times. In contrast, quite different risk factors were evident in residents who could not stand unaided, with a number of known fall risk factors (previous stroke, reduced ability to rise from a chair, slow reaction times) being associated with fewer falls. In this group, risk factors were intermediate versus nursing home care, poor health status, psychoactive medication use, Parkinson's disease, previous falls, and being able to get out of a chair. CONCLUSION: The findings indicate that there are different risk factors for falls for people living in residential aged care facilities who can and cannot stand unaided. These findings provide important information for developing fall-prevention strategies and suggest that those who can stand unaided but have multiple falls risk factors constitute the highest priority group for such interventions.

Accidental Falls↗

Nerve growth factor prevents experimental cisplatin neuropathy.

Cisplatin is a widely used antitumor agent, the dose-limiting toxicity of which is predominantly large-fiber sensory neuropathy. Prevention of such a neuropathy would extend the usefulness of this agent, allowing higher doses and longer periods of treatment. We report here that we have successfully established cisplatin neuropathy in mice measured by using behavioral, biochemical, and electrophysiological techniques, and that subcutaneous administration of human recombinant nerve growth factor (NGF) prevents or delays the neuropathy. Cisplatin administration reduced sensory ganglion levels of the peptide transmitter, calcitonin gene-related peptide, slowed nerve conduction in the tail and impaired proprioception as measured by the ability to balance on a rotating dowel. NGF coadministration appeared to prevent all these abnormalities. Treatment of the human toxic neuropathy with its well-established time of onset, simple clinical course, and the accessibility of nerve to NGF administered systemically may provide the best clinical setting for the first human trials of NGF.

Animals↗

Energy balance, insulin-related genes and risk of colon and rectal cancer.

Energy balance, or the ability to maintain body weight by balancing energy intake with energy expenditure, appears to be important in the etiology of colon cancer. One possible mechanism whereby energy balance may be associated with colorectal cancer is through its association with insulin. In our study, we evaluate the interaction between polymorphisms in 4 genes thought to be involved in insulin-related functions and components of energy balance with risk of colorectal cancer. Data from 2 population-based case-control studies of colon and rectal cancer conducted in Utah and Northern California were used to evaluate associations between body mass index (BMI), physical activity, energy intake and sucrose-to-fiber ratio and a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the G972R polymorphism of the IRS1 gene and the G1057D polymorphism of the IRS2 gene. A total of 1,346 incident colon cancer cases and 1,544 population-based controls and 952 incident rectal cancer cases and 1,205 controls were available for analysis. Inconsistent associations were identified between BMI, physical activity, energy intake and insulin-related genes. The 192/192 IGF1 genotype was associated with significant reduction in colon cancer risk among those with high physical activity (odds ratio [OR] 0.57; 95% confidence interval [CI] 0.39-0.83; p interaction 0.01). Although there was no significant pattern of interaction between either BMI or energy intake and polymorphisms assessed, specific sources of energy did appear to be more related to colon cancer risk in the presence of specific IRS2 and IGF1 genotypes. A high sucrose-to-fiber ratio increased risk of colon cancer in men who had the IRS2 DD genotype and among men who did not have the 192/192 IGF1 genotype. In summary, these data support the importance of components of energy balance in risk of colorectal cancer. Obesity, physical activity and energy intake appear to alter risk of colorectal cancer; however, the risk appears to be minimally influenced by genetic variants evaluated.

Adult↗

Practical implications of some recent studies in electrospray ionization fundamentals.

In accomplishing successful electrospray ionization analyses, it is imperative to have an understanding of the effects of variables such as analyte structure, instrumental parameters, and solution composition. Here, we review some fundamental studies of the ESI process that are relevant to these issues. We discuss how analyte chargeability and surface activity are related to ESI response, and how accessible parameters such as nonpolar surface area and reversed phase HPLC retention time can be used to predict relative ESI response. Also presented is a description of how derivitizing agents can be used to maximize or enable ESI response by improving the chargeability or hydrophobicity of ESI analytes. Limiting factors in the ESI calibration curve are discussed. At high concentrations, these factors include droplet surface area and excess charge concentration, whereas at low concentrations ion transmission becomes an issue, and chemical interference can also be limiting. Stable and reproducible non-pneumatic ESI operation depends on the ability to balance a number of parameters, including applied voltage and solution surface tension, flow rate, and conductivity. We discuss how changing these parameters can shift the mode of ESI operation from stable to unstable, and how current-voltage curves can be used to characterize the mode of ESI operation. Finally, the characteristics of the ideal ESI solvent, including surface tension and conductivity requirements, are discussed. Analysis in the positive ion mode can be accomplished with acidified methanol/water solutions, but negative ion mode analysis necessitates special constituents that suppress corona discharge and facilitate the production of stable negative ions.

Solvents↗

Flow-cytometric assessment of in vivo cytokine-producing monocytes in HIV-infected patients.

We have used two-color flow cytometry to study in vivo monocytic cytokine production at the single-cell level in HIV-infected patients. We demonstrated the presence of intracellular IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha in circulating CD14+ monocytes from HIV-infected patients. The specificity of intracellular staining with anti-cytokine antibodies was demonstrated by the suppression of the fluorescent signal when staining was performed in the presence of recombinant cytokines. We did not detect any specific intracellular staining when anti-IL-4 antibodies were used since monocytes do not produce IL-4. In vivo intracellular cytokine production of IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha was higher in monocytes from HIV-infected individuals compared to monocytes from healthy controls; however, only the data concerning IL-1 alpha reached statistical significance. Monocytic cytokines are involved in the regulation of HIV gene expression and may participate in the modulation of the Th1/Th2 balance. The ability to follow the production of a wide range of cytokines by circulating monocytes of HIV-infected patients should allow one to better analyze the role of monocytic cytokines in the pathogenesis of HIV disease.

Cytokines↗

Phenotypic analysis of mice lacking the highly abundant Purkinje cell- and bipolar neuron-specific PCP2 protein.

The Purkinje cell protein-2 (Pcp2, also known as L7) gene is abundantly expressed only in Purkinje cells of the cerebellum and bipolar neurons of the retina. The spatio-temporal expression pattern of this gene suggests a role for PCP2 in Purkinje cell development or normal cell physiology. A PCP2-deficient mouse was created by gene targeting to test the hypothesis that it is required for Purkinje cell development or function. Although normally present in abundance, the absence of PCP2 in null animals caused no observable cerebellar abnormalities. Behavioral analysis reveals normal abilities for balance and coordination. Null cerebellum has normal Purkinje cell numbers, morphology, and ultrastructure. Retinal bipolar neurons appear similarly unaffected. Aged null animals (22 months) were also examined and no deficits were detected using the same behavioral and histologic analyses. Although the null animal does not reveal the function of PCP2, it does rule out an essential role for PCP2 in Purkinje cell development, in Purkinje cell survival, and in at least some aspects of cerebellar function.

Animals↗

Effects of cationic liposome-DNA complexes on pulmonary surfactant function in vitro and in vivo.

Cationic liposome-DNA complexes are being evaluated as potential gene therapy agents for the lung. Cations have strong effects on the biophysical functions of lung surfactant. Therefore, we assessed whether cationic liposomes [composed of N-(1-(2,3-dioleyloxy) propyl)-N,N,N-trimethyl-ammonium chloride and dioleylphosphatidylethanolamine] with or without DNA affect behavior of four types of surfactant in vitro. Experiments were carried out using a modified Wilhelmy surface balance. The ability of surfactants that contain protein and anionic lipids to lower surface tension was inhibited in the presence of cationic liposomes. Inactivation was less when DNA was preincubated with cationic liposomes. Surfactant that contained neither protein nor anionic lipids was not inactivated. Mechanical properties of the lung were studied to assess in vivo surfactant function after intratracheal instillation of a cationic liposome-DNA complex into adult rats. Pressure-volume deflation curves were shifted by 18% compared with those from normal (untreated) animals, but this effect was transient and not different from that observed in animals who received a similar volume of saline. These findings indicate that cationic liposomes alone may have deleterious effects on behavior of some surfactants possibly by disrupting charge interactions between negatively charged phospholipids and surfactant proteins. When DNA is added to liposomes before exposure to surfactants, the adverse charge interactions may be obviated by charge neutralization of liposomes by DNA.

Animals↗

Reduced levels of PGE2 uptake by intact reno-medullary collecting tubule cells isolated from the spontaneously hypertensive rat and the identification of an intracellular PGE2 receptor/binding protein.

Prostaglandin E2 (PGE2) is thought to be involved in the control of NaCl loading in the kidney. Since the ability to balance salt concentrations across the nephron appears to be impaired in the Spontaneously Hypertensive Rat (SHR), the uptakes of PGE by isolated medullary collecting tubule cells (MCT) from both SH and normotensive (NT) rats were compared. A rabbit antiserum directed against PGE2 revealed by flow cytometry the active internalisation of exogenous ligand by a high density fraction of intact MCT cells from NT tissue. Conversely, PGE2 uptake by the same fraction was markedly reduced. The monoclonal antibodies (MoAbs) W2.44 and SH6.6 raised against a 45,000 X g fraction of medullary tissue and which blocked binding of the anti-PGE2 serum, identified by Western blotting, an intracellular PGE2 receptor or binding protein (PGER) of 16 k daltons. No alteration in the structure or level of expression of this antigen could be detected in the MCT fractions isolated from the SHR. It is suggested that an impairment of PGE2 membrane transport in the renal medulla may be a contributory factor to the SH condition.

Animals↗

Stem cell grand SLAM.

Stem cells in both embryonic and adult tissues are defined by their unique ability to balance self-renewal and differentiation such that mature cells necessary for tissue function can be generated and replaced without depletion of the stem cell pool. In this issue of Cell, report a major step forward for studying the mechanisms and regulation of such stem cell fate decisions in the blood-forming (hematopoietic) system by providing a simple and broadly applicable method to isolate these cells and to visualize them in their normal environment.

Animals↗

Long-term heavy marijuana users make costly decisions on a gambling task.

RATIONALE: Chronic marijuana use has been associated with impairments of learning, memory, and executive functions. Little is known, however, about the effects of marijuana use on other cognitive domains, such as decision-making, which are thought to play an important role in addiction and drug abuse. OBJECTIVES: The purpose of the present study was to determine if long-term heavy marijuana users employ different decision-making strategies than individuals with minimal marijuana exposure. METHODS: Volunteers were assigned to a cannabis (n = 10) or control group (n = 10) based upon history of prior marijuana use. Demographic and neuropsychological variables were evaluated, and a decision-making task--the gambling task (GT) was administered. RESULTS: Although few demographic and neuropsychological differences were noted between groups, marijuana users made more decisions that led to larger immediate gains despite more costly losses than controls. CONCLUSIONS: These data suggest that long-term heavy marijuana users may have specific deficits in the ability to balance rewards and punishments that may contribute to continued drug-taking behavior. It is unknown, however, whether the basis for such deficits might be attributed directly to marijuana exposure or pre-existing genetic or behavioral differences.

Adolescent↗