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At least 1,261 records · Page 70Linked to original sources

PubMed2003

Intraocular microablation of choroidal tissue by a 308 nm AIDA excimer laser for RPE-transplantation in patients with age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the western nations beyond 50 years of age. The most frequent cause for severe visual loss is the growth of neovascular membrances from the choroid into the subretinal space. This usually results in irreversible degeneration of the overlying retina. Surgical removal of the membrane is feasible, however, usually results in functional loss of apposing retinal photoreceptors since retinal pigment epithelial (RPE) cells are removed concurrently due to their tight adherence to the neovascular complex. Therefore, various attempts have been undertaken to fill the resulting RPE cell defect with either heterologous or autologous RPE cell transplants. So far cell survival, function and subsequent visual function has been disappointing. To minimize trauma and resulting dedifferentiation harvesting in the eye and transplantation in whole sheets and without temporary removal from the eyes would be desirable. This may be achieved by isolating grafts consisting of choroid, Bruch's membrance and RPE cells from the peripheral retina and transplantation of this graft under the neurosensory retina after removal of the choroidal neovascularization. However, the choroidal component of such a graft would be expected to interfere with diffusion of metabolites to and from the retina. Therefore, outcome would be expected to be better if the choroidal tissue would be removed before translocation. In preclinical experiments we used a 308 nm UV AIDA excimer laser to microablate choroidal tissue from such a graft in human donor eyes.

Choroid↗

PubMed1994

A morphological and functional assessment of Mycobacterium leprae-induced nerve damage in a guinea-pig model of leprous neuritis.

Nerve damage, resembling that caused by Mycobacterium leprae in man, was created by the injection of cobalt-irradiated M. leprae organisms into the tibial nerve of guinea-pigs. Assessment of nerve damage was made by clinical, electrophysiological and morphometric means at intervals up to 13 weeks after injection. Quantitative immunohistochemical analysis of neuropeptide-containing fibres in the skin of the foot was also carried out. Significant nerve damage occurred 3 weeks after injection of M. leprae organisms. Motor and sensory functional loss peaked at 5 weeks after injection, and there was a significant decrease of peptide-immunoreactive nerves in all skin compartments. The nerve damage was self-limiting and functional recovery had occurred by 13 weeks. The model shows many of the features found in the nerve damage of treated leprosy patients.

Animals↗

PubMed1976

Axonal excitability and motor propagation velocity of peripheral nerves in patients with acute vascular lesions of the brain.

From measurements of maximum and minimum motor nerve propagation velocity and neuronal excitability we conclude that there is a functional loss of motor units and distal nerve "dying back" in persons affected with unilateral acute cerebral vascular lesions. The study also suggests that transynaptic degeneration affects the lower motor neurone function on both sides.

Acute Disease↗

PubMed2004

Evolving therapeutic strategies for Duchenne muscular dystrophy: targeting downstream events.

Duchenne muscular dystrophy (DMD) is a progressive, lethal, muscle wasting disease that affects 1 of 3500 boys born worldwide. The disease results from mutation of the dystrophin gene that encodes a cytoskeletal protein associated with the muscle cell membrane. Although gene therapy will likely provide the cure for DMD, it remains on the distant horizon, emphasizing the need for more rapid development of palliative treatments that build on improved understanding of the complex pathology of dystrophin deficiency. In this review, we have focused on therapeutic strategies that target downstream events in the pathologic progression of DMD. Much of this work has been developed initially using the dystrophin-deficient mdx mouse to explore basic features of the pathophysiology of dystrophin deficiency and to test potential therapeutic interventions to slow, reverse, or compensate for functional losses that occur in muscular dystrophy. In some cases, the initial findings in the mdx model have led to clinical treatments for DMD boys that have produced improvements in muscle function and quality of life. Many of these investigations have concerned interventions that can affect protein balance in muscle, by inhibiting specific proteases implicated in the DMD pathology, or by providing anabolic factors or depleting catabolic factors that can contribute to muscle wasting. Other investigations have exploited the use of anti-inflammatory agents that can reduce the contribution of leukocytes to promoting secondary damage to dystrophic muscle. A third general strategy is designed to increase the regenerative capacity of dystrophic muscle and thereby help retain functional muscle mass. Each of these general approaches to slowing the pathology of dystrophin deficiency has yielded encouragement and suggests that targeting downstream events in dystrophinopathy can yield worthwhile, functional improvements in DMD.

Animals↗

PubMed2005

Strategies to create a regenerating environment for the injured spinal cord.

Spine cord injury (SCI) leads to devastating functional loss below the level of injury. Partially explained by the presence of a non-permissive environment, the injured spinal cord does not mount adequate regeneration to re-establish functional connections. Therefore, it is important to identify the cellular and molecular factors and their interactions that affect axonal regeneration within the changed environment. This review will discuss the current understanding of the neuronal and glial factors and the extracellular matrix in the spinal cord that inhibit axonal growth, and it will summarize some major approaches for facilitation of regeneration. The strategies are classified into the following categories: penetration of the blood-brain barrier; modulation of caspase activity to reduce apoptosis; stem cells and tissue implantation; administration of neurotrophic factors, including viral vector-mediated delivery; and modulation of the extracellular matrix. Although recent studies on genomic regulation and apoptosis have identified particularly important molecular targets, more is necessary to achieve long-term regeneration. A combination of the approaches targeting various aspects in the regenerating environment would be more effective than a single strategy. Overall, insights arising from the experimental results may eventually lead to better therapeutic intervention so as to lessen the functional disability and enhance the quality of life in patients with SCI.

Animals↗

PubMed1990

Implication of altered pulmonary function in pneumonectomy for tuberculous destroyed lung.

Twelve patients undergoing pneumonectomy for tuberculous destroyed lung were studied to determine the value of preoperative spirometry in the assessment of their pulmonary reserve, and prediction of their post-operative morbidity. Preoperatively, the functional losses were evidenced by mean values of FVC of 56.4%, FEV1 of 48.9% and PEFR of 65.8%--all expressed as percentage of predicted normals. No significant alteration occurred in pulmonary function post-pneumonectomy. All patients were in Class 1 (HYHA) pre- and post-operatively. It is concluded that operability in these patients cannot be based on spirometry alone but must include the preoperative assessment of clinical (symptomatic) stage and cardiovascular status.

Adolescent↗

PubMed2002

Elbow extension.

Reconstruction of elbow extension is an established treatment with a high degree of patient satisfaction. The D-T transfer is the most common method and has the advantage of inducing no serious complications; however, it necessitates a long period of healing and recovery. The Bi-T transfer is used much less frequently and, in the author's opinion, has few advantages compared with the D-T transfer. It is somewhat less time consuming to perform, and the rehabilitation period is a few weeks shorter. This method, however, has several drawbacks, including difficulties in learning to use the muscle as an extensor and a reduction of elbow flexion strength, which might result in a subjective functional loss. What is the best treatment for patients with a posterior deltoid that has a strength grade of 2 or 3: a D-T or Bi-T transfer or functional electrical stimulation? Today, this question is impossible to answer. The author is convinced that the optimal postoperative regimen for a reconstructed elbow extension has not been found yet.

Activities of Daily Living↗

PubMed1999

Interactions of HIV-1 with antigen-presenting cells.

There is currently much interest in the numerical and functional loss of antigen-presenting cells (APC) in HIV-1 disease and the contribution that this may make to HIV-1 pathology. The HIV-1 virus can interfere with the normal function of APC in a number of ways involving inappropriate signalling. These include changes in cytokine balance, cell-surface molecule expression and intracellular signalling pathways. This review examines how HIV-1 is able to disregulate APC function and discusses possible outcomes for the function of the immune system.

Antigen-Presenting Cells↗

PubMed2000

The patterns of late deterioration in patients with transitional lipomyelomeningocele.

INTRODUCTION: Tethering is assumed to be the primary cause of deterioration seen in children with transitional lipomyelomeningocele as they age. The inevitability of deterioration has led to recommendations for prophylactic interventions to stabilize or prevent further clinical deterioration. OBJECTIVE: Determine the frequency and patterns of functional deterioration observed after successful untethering in patients with transitional lipomyelomeningocele and compare functional outcomes with what is known regarding untreated patients. METHODS: Fifty patients having transitional LMMC, treated at a single institution and followed in a multidisciplinary clinic were retrospectively reviewed to determine their clinical status prior to untethering, and the time to development of new symptoms or signs following untethering. RESULTS: 82% of patients were diagnosed and 78% underwent untethering prior to one year of age. All patients had a cutaneous lumbosacral lipoma, 22 patients were considered normal at presentation and 28 showed abnormalities on clinical examination. Forty-nine patients were untethered successfully and all were available for follow-up ranging from 2 to 138 months (mean 39 months). Acute morbidity was limited to transient neurogenic bladder dysfunction and minor wound complications. Late clinical deterioration occurred in the majority of patients. Orthopedic and neurological deterioration occurred over the first 60 months following untethering and urological deterioration occurred thereafter. CONCLUSIONS: Functional loss after untethering is common and the pattern of loss is likely a reflection of the ability to detect abnormalities in this infant population. Untethering does not usually result in permanent acute morbidity, and does not prevent longer-term functional deterioration. The ratio of asymptomatic to symptomatic patients at follow-up in this operative series is similar to age-matched historical series of untreated patients.

British Columbia↗

PubMed2004

Local estimation of posterior class probabilities to minimize classification errors.

Decision theory shows that the optimal decision is a function of the posterior class probabilities. More specifically, in binary classification, the optimal decision is based on the comparison of the posterior probabilities with some threshold. Therefore, the most accurate estimates of the posterior probabilities are required near these decision thresholds. This paper discusses the design of objective functions that provide more accurate estimates of the probability values, taking into account the characteristics of each decision problem. We propose learning algorithms based on the stochastic gradient minimization of these loss functions. We show that the performance of the classifier is improved when these algorithms behave like sample selectors: samples near the decision boundary are the most relevant during learning.

Probability↗

PubMed1990

Measurement and prediction of functional capacity in Alzheimer's disease.

Functional loss in Alzheimer's disease is difficult to measure or predict. The Blessed Dementia Rating Scale (Part 1) correlates well with postmortem changes but is not an effective antemortem index of functional change since disparate behavioral domains are assessed. We performed a factor analysis of the Blessed items in 187 patients with clinically diagnosed Alzheimer's disease and identified 4 independent factors: (I) cognitive, (II) personality, (III) apathy, and (IV) basic self-care. An endpoint, consisting of a score indicative of moderate disability, was determined for each factor. We then used life table analyses to compare the probability of reaching these endpoints over time in longitudinally followed patients. Patients with extrapyramidal signs at their initial visit reached the factor IV endpoint sooner, and those with psychosis or no family history of dementia also reached the factor I endpoint faster. These data illustrate the utility of a multifactorial approach to the assessment of functional capacity in Alzheimer's disease, and also indicate that extrapyramidal symptoms and psychosis are powerful predictors of the rate of decline in basic self-care activities and cognition.

Aged↗

PubMed1981

Ureteropelvic junction obstruction in infants and children: functional evaluation of the obstructed kidney preoperatively and postoperatively.

We evaluated 14 children with primary ureteropelvic junction obstruction, using preoperative excretory urography and renal imaging with the renal cortical labeling agent 99mtechnetium dimercaptosuccinic acid. All children with a reduction in function of 10 per cent or more in the obstructed kidney had severe calicectasis; others with severe calicectasis had minimal functional loss. Renal scanning with dimercaptosuccinic acid discourages surgery in the questionably obstructed kidney and encourages repair in the severely obstructed kidney. In 10 children who had followup renal imaging after repair relative function was not significantly different.

Adolescent↗

PubMed2001

Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity.

Deficits in a variety of different neurochemical species are consistent with a loss of cortical gamma-aminobutyric acid (GABA)ergic interneurons in schizophrenia. As well as neurochemical markers that indicate all neurons using GABA as a transmitter, and which include GABA uptake sites and glutamate decarboxylase, deficits of certain neuropeptides and calcium binding proteins coexisting with GABA have been reported. These abnormalities are indicative of losses specific to certain subtypes of GABAergic neurons. The calcium binding proteins in particular demonstrate selective deficits; we find losses of parvalbumin- and calbindin-, but not calretinin-immunoreactive cells in the prefrontal cortex in schizophrenia. These selective reductions in the density of parvalbumin- and calbindin-containing neurons could reflect functional loss of expression in intact cells or alternatively a deficit in the density of certain GABAergic neuronal subtypes. The latter interpretation is consistent with a neurodevelopmental pathogenesis involving neuronal damage at a time prior to the expression of these protective calcium-binding proteins. In this review we discuss the evidence for altered GABAergic transmission in schizophrenia.

Biomarkers↗

PubMed2003

Does late-life physical activity or exercise prevent or minimize disablement? A critical review of the scientific evidence.

Physical activity and exercise are widely purported to enhance health and minimize or prevent functional loss and disability. Yet, do the benefits of late-life physical activity or exercise extend beyond disease and impairment-level factors? Does late-life physical activity minimize or prevent functional limitations and disability? To address these questions, a best-evidence framework was used to examine the effects of late-life physical activity on disablement outcomes. This review shows that exercise-particularly walking-increases muscle strength and aerobic capacity and reduces functional limitations. It is less clear, however, whether physical activity or exercise prevents or minimizes physical disability. Furthermore, this review shows a discrepancy between prospective and experimental studies: several well-conducted prospective studies show a beneficial effect of physical activity on minimizing disability, whereas the majority of experimental studies that have examined disability as an outcome do not show improvements in disability. Three research priorities are identified that would advance the science in this field: (1). development of a clear conceptual and theoretical framework of late-life physical activity and assessment; (2). use of a disablement outcomes framework to examine the outcomes of late-life physical activity; and (3). development of a mechanism of action explaining the relationship between physical activity and exercise and disablement outcomes.

Activities of Daily Living↗

PubMedDate not supplied

Age and physical work capacity.

Aging is associated with a progressive decrement in various components of physical work capacity, including aerobic power and capacity, muscular strength and endurance, and the tolerance of thermal stress. A part of the functional loss can be countered by regular physical activity, control of body mass, and avoidance of cigarette smoking. Nevertheless, athletes who continue to train regularly still show a substantial aging of both physiological function and competitive performance, reflecting a deterioration of cardiac pump function, a decrease of muscle strength, and a progressive impairment of heat tolerance. These various changes are of concern to the occupational physician, because of the rising average age of the labor force. In theory, an over-taxing of the heart and skeletal muscles might be thought to lead to a decrease of productivity, manifestations of worker fatigue such as absenteeism, accidents, and industrial disputes, and an increased susceptibility to musculoskeletal injuries, heart attacks, and strokes. However, in practice, the productivity, health, and safety of the older worker pose relatively few problems. Reasons for this paradox are discussed, and it is stressed that in general there is no longer need to push workers to their physical limits because of automation-related changes in methods of production.

Aging↗

PubMed2005

Decision-theoretic views on simultaneous testing of superiority and noninferiority.

In a simultaneous testing of noninferiority and superiority in clinical trials, there is no multiplicity penalty. Ng (2003), however, argues that even though there is no inflation of the Type I error rate, this type of simultaneous testing is problematic because it may lead to loss of power in the subsequent confirmatory trial. And he recommends to conduct only one test chosen on the basis of the sponsor's preliminary assessment. We view the question of whether one should simultaneously test for noninferiority and superiority from a decision-theoretic view point. We develop the loss function approach implicit in Ng's research and compare his recommendation to simultaneous testing procedures indexed by a variety of design parameters. We find that the simultaneous testing procedure generally provides smaller loss than Ng's method, except when the prior distribution allocates a large probability to equivalence of the two treatments.

Clinical Trials as Topic↗

PubMed1989

Coverage of acute vascular injuries of the axilla and groin with transposition muscle flaps: case reports.

Acute axillary or groin vascular injuries caused by farm machinery or shotgun blasts are often associated with extensive soft-tissue loss. Coverage of the repaired blood vessels with healthy tissue is necessary to avoid infection, desiccation, pseudoaneurysm, and rupture. Adjacent muscles are not always available to rotate for coverage, due to unacceptable functional loss, or injury to the principal vascular pedicle. We used proximally based trunk musculature with vascular pedicles out of the areas of injury to achieve coverage of four extensive axillary wounds and one extensive groin wound. Arterial repair only was performed in three axillary wounds. Combined arterial and venous repair were performed in one groin wound and one axillary wound. Followup ranging from 9 months to 5 years revealed no vascular failure or soft-tissue complications. We conclude that coverage of vascular repairs and soft-tissue defects with viable muscle is necessary in cases of extensive injury. Adjacent muscle is preferred for coverage, but when this is unavailable, coverage can still be achieved using more proximally pedicled muscles of the trunk.

Adolescent↗

PubMed2006

Simple and multiple P-splines regression with shape constraints.

In many research areas, especially within social and behavioural sciences, the relationship between predictor and criterion variables is often assumed to have a particular shape, such as monotone, single-peaked or U-shaped. Such assumptions can be transformed into (local or global) constraints on the sign of the nth-order derivative of the functional form. To check for such assumptions, we present a non-parametric regression method, P-splines regression, with additional asymmetric discrete penalties enforcing the constraints. We show that the corresponding loss function is convex and present a Newton-Raphson algorithm to optimize. Constrained P-splines are illustrated with an application on monotonicity-constrained regression with both one and two predictor variables, using data from research on the cognitive development of children.

Algorithms↗