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Biomedical subjects

E Dean

Publications and source records attributed to E Dean.

At least 19 recordsLinked to original sources
PubMed1997

Oxygen transport deficits in systemic disease and implications for physical therapy.

The purposes of this article are to discuss the effects of some common systemic diseases on cardiopulmonary function and oxygen transport and to describe the implications for physical therapists. Pathology of every major organ system can manifest secondary effects on cardiopulmonary function and oxygen transport. Such effects are of considerable clinical significance given that they can be life threatening and that physical therapy usually stresses the oxygen transport system. This article reviews the cardiopulmonary effects of hematologic, neuromuscular, musculoskeletal, gastrointestinal, hepatic, renal, collagen vascular and connective tissue, endocrine, and immunologic conditions. The cardiopulmonary manifestations of some common nutritional disorders (eg, obesity, anorexia nervosa) are also discussed. Physical therapists need to be able to anticipate, detect, and manage the cardiopulmonary manifestations of systemic disease given medical advances and the increasing number of patients with multisystem problems, the aging of the population, the expanding scope of physical therapy practice, and the increased professional and ethical responsibility associated with direct patient access.

Aged↗
PubMed1996

Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus.

The excitatory, glutamatergic granule cells of the hippocampal dentate gyrus are presumed to play central roles in normal learning and memory, and in the genesis of spontaneous seizure discharges that originate within the temporal lobe. In localizing the two GABA-producing forms of glutamate decarboxylase (GAD65 and GAD67) in the normal hippocampus as a prelude to experimental epilepsy studies, we unexpectedly discovered that, in addition to its presence in hippocampal nonprincipal cells, GAD67-like immunoreactivity (LI) was present in the excitatory axons (the mossy fibers) of normal dentate granule cells of rats, mice, and the monkey Macaca nemestrina. Using improved immunocytochemical methods, we were also able to detect GABA-LI in normal granule cell somata and processes. Conversely, GAD65-LI was undetectable in normal granule cells. Perforant pathway stimulation for 24 hours, which evoked population spikes and epileptiform discharges in both dentate granule cells and hippocampal pyramidal neurons, induced GAD65-, GAD67-, and GABA-LI only in granule cells. Despite prolonged excitation, normally GAD- and GABA-negative dentate hilar neurons and hippocampal pyramidal cells remained immunonegative. Induced granule cell GAD65-, GAD67-, and GABA-LI remained elevated above control immunoreactivity for at least 4 days after the end of stimulation. Pre-embedding immunocytochemical electron microscopy confirmed that GAD67- and GABA-LI were induced selectively within granule cells; granule cell layer glia and endothelial cells were GAD- and GABA-immunonegative. In situ hybridization after stimulation revealed a similarly selective induction of GAD65 and GAD67 mRNA in dentate granule cells. Neurochemical analysis of the microdissected dentate gyrus and area CA1 determined whether changes in GAD- and GABA-LI reflect changes in the concentrations of chemically identified GAD and GABA. Stimulation for 24 hours increased GAD67 and GABA concentrations sixfold in the dentate gyrus, and decreased the concentrations of the GABA precursors glutamate and glutamine. No significant change in GAD65 concentration was detected in the microdissected dentate gyrus despite the induction of GAD65-LI. The concentrations of GAD65, GAD67, GABA, glutamate and glutamine in area CA1 were not significantly different from control concentrations. These results indicate that dentate granule cells normally contain two "fast-acting" amino acid neurotransmitters, one excitatory and one inhibitory, and may therefore produce both excitatory and inhibitory effects. Although the physiological role of granule cell GABA is unknown, the discovery of both basal and activity-dependent GAD and GABA expression in glutamatergic dentate granule cells may have fundamental implications for physiological plasticity presumed to underlie normal learning and memory. Furthermore, the induction of granule cell GAD and GABA by afferent excitation may constitute a mechanism by which epileptic seizures trigger compensatory interictal network inhibition or GABA-mediated neurotrophic effects.

Animals↗
PubMed1996

Apoptosis and necrosis induced in different hippocampal neuron populations by repetitive perforant path stimulation in the rat.

Patients experiencing spontaneous seizures of temporal lobe origin often exhibit a shrunken hippocampus, which results from the loss of dentate granule cells, hilar neurons, and hippocampal pyramidal cells. Although experimental attempts to replicate the human pattern of hippocampal sclerosis in animals indicate that prolonged seizures cause prominent injury to dentate hilar neurons and hippocampal pyramidal cells, dentate granule cells of animals are generally regarded as relatively resistant to seizure-induced injury. By evaluating pathology shortly after hippocampal seizure discharges were induced electrically, we discovered that some granule cells are highly vulnerable to prolonged excitation and that they exhibit acute degenerative features distinct from those of other vulnerable cell populations. Intermittent perforant path stimulation for 24 hours induced acute degeneration of dentate granule cells, dentate hilar neurons, and hippocampal pyramidal cells. However, stimulation for 8 hours, which was insufficient to injure hilar neurons and hippocampal pyramidal cells, was nonetheless sufficient to induce bilateral granule cell degeneration. Degenerating granule cells were consistently more numerous in the infrapyramidal than the suprapyramidal blade, and were consistently more numerous in the rostral than caudal dentate gyrus. Depending on the nature of the insult, acutely degenerating neurons exhibit distinct morphological features that are classifiable as either apoptosis or necrosis, although the degree of possible overlap is unknown. Light and electron microscopic analysis of the acute pathology caused by prolonged afferent stimulation revealed that degenerating hilar neurons and pyramidal cells exhibited the morphological features of necrosis, which is characterized in part by early cytoplasmic vacuolization before nuclear changes occur. However, acutely degenerating granule cells exhibited the clearly distinct morphological features of apoptosis, which include an early coalescence of nuclear chromatin into multiple nuclear bodies, compaction of the cytoplasm, cell shrinkage, and budding-off of 'apoptotic bodies' that are engulfed by glia. Whereas pyramidal cell debris persisted for months, granule cell debris disappeared rapidly. This observation may explain why significant granule cell vulnerability has not been described previously. These data document for the first time that dentate granule cells are among the cell types most vulnerable to seizure-induced injury, and demonstrate that whereas hilar neurons and pyramidal cells undergo a typically necrotic degenerative process, granule cells simultaneously exhibit morphological features that more closely resemble the degenerative process of apoptosis. This finding implies that the type of cell death induced by excessive excitation may be determined postsynaptically by the way in which different target cells 'interpret' an excitatory insult. This experimental model may be useful for identifying the biochemical mechanisms that initiate and mediate neuronal apoptosis and necrosis, and for developing strategies to prevent or induce these presumably distinct forms of neuronal death.

Afferent Pathways↗
PubMed1993

Adrenalectomy-induced granule cell degeneration in the rat hippocampal dentate gyrus: characterization of an in vivo model of controlled neuronal death.

The recent discovery that adrenalectomy results in hippocampal granule cell loss suggested that this phenomenon might be useful as a model of selective, experimentally controlled neuronal death possibly relevant to neurodegenerative disorders. This study was designed to provide a detailed qualitative anatomical description of the phenomenon and to determine whether adrenalectomy-induced dentate granule cell degeneration constitutes a reliable model of selective neuronal death. Silver impregnation staining revealed that granule cell degeneration begins immediately after adrenalectomy and continues for months in both sexes, in young and older adults, and in all strains tested. In one group of 77 adrenalectomized rats, 82% exhibited silver-impregnated granule cells. This phenomenon is extraordinarily selective in that no neurons other than dentate granule cells degenerated after adrenalectomy. There was considerable variability among animals in the number of cells degenerating at a given time-point or in the degree of ultimate cell loss. In the most extreme cases, virtually complete granule cell loss was present throughout approximately 80% of the dentate gyrus. Nissl staining revealed that degenerating granule cells exhibited coalescing of nuclear chromatin into multiple nuclear bodies and pyknosis without accompanying glial swelling. This morphology is distinct from the necrosis caused by other neurotoxic insults and is the subject of the ultrastructural companion paper identifying this type of cell death as apoptosis. Taken together, these results indicate that adrenalectomy reliably initiates an immediate, highly selective, and long-continuing process of hippocampal granule cell degeneration that exhibits morphological features characteristic of apoptosis, rather than necrosis. The possibility that this apoptotic cell death involves a biochemical cascade relevant to programmed cell death and/or neurodegenerative diseases suggests that this model may be valuable for studies of neuronal death and its prevention. Some practical guidelines for use of this model are described.

Adrenalectomy↗
PubMed1993

Electron microscopic analysis of adrenalectomy-induced hippocampal granule cell degeneration in the rat: apoptosis in the adult central nervous system.

As described in the preceding paper, adrenalectomy triggers hippocampal granule cell degeneration that begins within days after adrenalectomy, continues for months, and is the only apparent cell death anywhere within the brain. At the light microscopic level, granule cell degeneration is characterized by coalescing of nuclear chromatin into numerous spherical bodies. Since the morphology at the light microscopic level resembled the nuclear morphology characteristic of "apoptosis" rather than "necrosis," we undertook this ultrastructural study to determine if adrenalectomy induces the morphological features characteristic of apoptosis. Electron microscopy revealed coalescing of nuclear chromatin, compaction of cytoplasm, and the budding-off of cytoplasmic bodies that were engulfed by glia. Mitochondria, the Golgi apparatus, and rough endoplasmic reticulum appeared relatively normal early in the process of granule cell degeneration when nuclear changes were prominent. Presynaptic terminals innervating degenerating granule cells appeared normal. Electron-dense degeneration of granule cell axon terminals in association with normal postsynaptic elements of CA3 pyramidal cells highlighted the extraordinary selectivity of adrenalectomy-induced granule cell death. Ten weeks after adrenalectomy, astrocytes were filled with abnormally abundant glial fibrils and neuronal debris. This "apoptotic" morphology produced by adrenalectomy was clearly distinct from the "necrotic" granule cell morphology produced by intrahippocampal injection of the neurotoxin volkensin. These results indicate that, in a manner possibly analogous to castration-induced prostate cell death, loss of adrenal hormone triggers a process in dentate granule cells that causes the morphological changes characteristic of "apoptosis." Thus, adrenal steroids may be obligatory growth factors for dentate granule cells and their loss may initiate a selective process in the mature brain that is unique or that may normally occur only in the developing brain.

Adrenalectomy↗
PubMed1993

Calbindin-D28k immunoreactivity and selective vulnerability to ischemia in the dentate gyrus of the developing rat.

Hippocampal dentate granule cells normally express the calcium-binding protein calbindin-D28k and, in the adult, are the hippocampal neurons least vulnerable to an ischemic insult. We evaluated hippocampal structure 2-3 days after hypoxic/ischemic insult at postnatal day 7-10, and discovered that, unlike adult granule cells, developing granule cells were irreversibly injured. Localization of calbindin-D28k-like immunoreactivity (LI) revealed that the vulnerable cells were the immature granule cells at the base of the cell layer that were not yet calbindin-immunoreactive. Adjacent granule cells that did not die in response to the hypoxic/ischemic insult were calbindin-immunoreactive. Whether the lack of calbindin-LI in immature granule cells is causally related to their vulnerability, or is a coincidental reflection of cellular immaturity, remains to be determined.

Animals↗
PubMed1993

Movement energetics of individuals with a history of poliomyelitis.

Principles for evaluating the functional capacity of, and, therefore, exercise testing, chronically-disabled populations such as individuals with a history of poliomyelitis are considerably less well established than those for able-bodied persons. Therefore, we examined the use of indexes of movement economy and cardiorespiratory conditioning based on the results of a submaximal exercise test and oxygen consumption studies in individuals with a history of poliomyelitis. Subjects (n = 48) were categorized into four distinct groups, ie, having normal movement economy and either normal (n = 12) or reduced cardiorespiratory conditioning (n = 11), or having reduced movement economy and either normal (n = 10) or reduced cardiorespiratory conditioning (n = 15). There was no relationship between the indexes of movement economy and cardiorespiratory conditioning (p > 0.05) supporting that these indexes reflected physiologically-distinct entities. Irrespective of movement economy, deconditioned subjects had a reduced forced vital capacity (% predicted) (p < 0.05) and a higher resting heart rate (HR) (p < 0.01) compared to conditioned subjects. The difference in resting HR was attributed to conditioning level rather than initial arousal because resting HR and VO2 were comparable on repeated tests (p > 0.05). Although there was no difference in steady-state HR (% predicted maximum) among the four groups (p > 0.05), VO2 (% pred max) was significantly lower for the deconditioned than the conditioned subjects (p < 0.01). We concluded that determining movement economy and cardiorespiratory conditioning with a submaximal exercise test may enhance assessment and treatment outcome evaluation, hence provide a rational basis for rehabilitation interventions in individuals with a history of poliomyelitis.

Adult↗
PubMed1993

Relationships among cane fitting, function, and falls.

BACKGROUND AND PURPOSE: Although canes are among the most commonly used mobility aids, little is known about the relationship between cane prescription and effectiveness. The purpose of this study was to examine the relationships among cane fitting (ie, cane fitter, cane band, and cane length), reported improvements in function, and reduction in falls. SUBJECTS AND METHODS: Cane users living in the community (86 women and 58 men with a median age distribution of 61 to 80 years) and sampled from seven urban shopping centers in British Columbia, Canada, participated in the study. The primary reasons cited for using a cane were joint problems (39%), general balance difficulties (30%), and a combination of joint and balance problems (15%). Measures included appropriateness of cane length and responses to closed-ended questions related to qualifications of the cane fitter, cane band, functional ability with a cane, and falling frequency. RESULTS: Overall, cane use was associated with improved confidence and functional ability. Canes fitted by health care workers approximated the clinically recommended length compared with canes fitted by non-health care workers, which tended to be greater than this length. There was no relationship, however, between cane fitting (cane fitter, cane hand, and appropriateness of cane length) and functional ability with a cane and falling frequency [corrected]. CONCLUSION AND DISCUSSION: We concluded that health care workers may need to reconsider the variables for optimal cane prescription and their specifications for a given individual. The notion of a correct length and cane hand, for example, may be less important than factors such as the indications for cane use, comfort, and enhanced confidence.

Accidental Falls↗
PubMed1992

The effect of postural drainage positioning on ventilation homogeneity in healthy subjects.

Body position is known to have significant effects on oxygen transport. These effects, however, are seldom considered during postural drainage (PD). The purpose of this study was to examine the effect of modified PD positions on ventilation homogeneity (the evenness of the distribution of ventilation), which is a key component of oxygen transport. The single-breath nitrogen washout test was used to obtain an index of ventilation homogeneity (slope of phase 3 [SBN2/L%]). Seventeen healthy individuals, ranging from 22 to 40 years of age ( mean = 28.4, SD = 5.6), performed the single-breath nitrogen test while sitting, lying supine with the bed tipped head down, right side lying, and right side lying with the bed tipped head down. Within-subject one-way analyses of variance and Tukey's post hoc analyses were used to compare differences in SBN2/L% across the four positions. The distribution of ventilation was significantly less homogeneous in the side-lying positions compared with the supine and sitting positions. Although these results reflect a position-induced change in pleural pressure gradient, they also reflect the effect of gravity-independent, intraregional changes on ventilation distribution. Thus, modified PD positioning has a significant effect on ventilation homogeneity, which may predispose a patient to arterial desaturation. Given the complexity of the factors involved, patients considered for PD positioning should be monitored for arterial saturation.

Adult↗
PubMed1992

Discordance of airflow limitation and ventilatory inhomogeneity in asthma and cystic fibrosis.

Although it is known that both airflow rates and gas distribution are impaired in asthma and cystic fibrosis (CF), the concordance of the change in these defects between two points in time has not been studied. On two separate occasions, the FEV1, FVC and slope of Phase III (SBN2/L%) of the single breath nitrogen test were determined, as well as the concordance between the change in these indices in 14 healthy subjects, 14 subjects with asthma, and seven subjects with CF. The coefficient of variation within a test session averaged less than 5% for the FEV1 and less than 10% for the SBN2/L% within each group. The change in FEV1 correlated with the change in FVC in all three groups, but did not correlate with the change in SBN2/L% in any group. In seven of the 14 cases of asthma and six of the seven cases of CF (outliers), the differences in the indices (expressed as the change in percent predicted) were greater than the differences observed in the control group. In three of the asthmatic and four of the CF outliers, the changes were as predicted, that is, both tests returned toward normal, or both became more abnormal. In two of the asthmatic and CF outliers both the FEV1 and SBN2/L% increased, while both decreased in the other two asthmatic outliers. Although some of the same factors will affect both indices, a worsening of ventilation inhomogeneity, which will affect the SBN2/L%, could occur with an improvement in ventilatory flow rate. Alternatively, airflow limitation could worsen but be accompanied by an improvement in ventilation homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Clinical decision making in the management of the late sequelae of poliomyelitis.

Years after the initial onset of poliomyelitis, patients often report new problems, including fatigue, weakness, pain, breathing difficulty, decreased endurance, problems with swallowing, choking, increased sensitivity to cold, and psychological problems. The premise of this article is that underlying pathophysiology of these problems can be assessed on the basis of a detailed history, a multisystem physical examination, and supplemental information provided by investigative tests. The indications for treatment of the late sequelae of poliomyelitis based on the underlying pathophysiology and the rationale for treatment prescription are explored. Possible outcomes of the assessment include no intervention; prescription of a balance between activity and rest, a reduction in activity, or an increase in activity; interventions to improve postural alignment, prescription of orthoses, and weight control; prescription of walking aids and mobility devices; respiratory care; lifestyle modification; or some combination of these outcomes. If treatment can be directed at the underlying causes of the late sequelae, the possibility of reducing further deterioration and of optimizing function in these patients will likely be enhanced.

Diagnosis, Differential↗
PubMed1991

Pulmonary function in individuals with a history of poliomyelitis.

We examined the relationship between the lung function of 74 individuals with a history of poliomyelitis and reports of shortness of breath during activities of daily living, and the presence of post-polio sequelae risk factors. First, we studied the spirometry of 60 individuals (group 1) and second, we studied the relationship between the spirometry of an additional 14 individuals (group 2) and their respiratory muscle strength (Pimax and Pemax). In both groups, we examined the relationship between factors associated with post-polio sequelae including ventilation at polio-onset, having contracted polio after the age of 10, and having had polio for over 35 years; and lung function. In group 1, the FEV1 and FVC were lower for individuals with shortness of breath than individuals without (p less than 0.01). With respect to risk factors, FEV1 and FVC were lower in individuals who were ventilated at polio-onset, in individuals who contracted polio over 10 years of age, and in individuals who had had polio for less, rather than more than 35 years (p less than 0.05). The results for group 2 were comparable to group 1. In addition, the observed Pimax and Pemax were significantly lower than predicted values (p less than 0.05). Although FEV1 and FVC were positively correlated with both Pimax and Pemax (p less than 0.05), Pemax was disproportionately impaired compared to Pimax (40 +/- 12.1 and 82 +/- 38.8 percent predicted respectively). We conclude that individuals with a history of poliomyelitis can have compromised lung function irrespective of shortness of breath, that risk factors such as ventilation at polio-onset and polio-onset after 10 years of age can help predict those at risk of respiratory compromise, and that the measurement of respiratory muscle strength and of Pemax in particular, can augment the assessment of lung function of these individuals. Such assessment may avert respiratory complications in the post poliomyelitis population including those secondary to health care interventions.

Adult↗
PubMed1991

Effect of modified aerobic training on movement energetics in polio survivors.

Given that individuals with disabilities may be unable to achieve maximal oxygen uptake in an exercise test and that maximal exercise testing may cause increased fatigue, pain, and muscle weakness, we examined the role of submaximal exercise testing and training based on objective as well as subjective parameters in polio survivors. Experimental (N = 7) and control subjects (N = 13) were tested before and after a 6-week period. The experimental subjects participated in a 6-week exercise training program for 30 to 40 minutes, three times a week. The program consisted of treadmill walking at 55% to 70% of age-predicted maximum heart rates; however, exercise intensity was modified to minimize discomfort/pain and fatigue. Neither objective nor subjective exercise responses were significantly different in the control group over the 6 weeks. No change was observed in cardiorespiratory conditioning in the experimental group. However, movement economy, which is related to the energy cost of walking, was significantly improved; and walking duration was significantly increased at the end of training. Modified aerobic training may have a role in enhancing endurance and reducing fatigue during activities of daily living in polio survivors.

Adult↗
PubMed1990

Semitendinosus repair augmentation of acute anterior cruciate ligament rupture.

The semitendinosus tendon has been used since 1980 by the senior author (J.P.M) to augment anterior cruciate ligament repair surgery in cases of acute rupture. There are two major criticisms of this technique: first, the semitendinosus tendon lacks adequate tensile strength functionally to replace the normal anterior cruciate ligament; and second, the semitendinosus is an important hamstring muscle, the loss of which has the potential to weaken the dynamic control of the knee. Objective measurement of success or failure of this procedure is provided by KT1000 arthrometer laxity testing for static recovery of stability, and by Cybex isokinetic dynamometer testing of peak torque and fatigue index to evaluate muscular rehabilitation. Thirty-seven patients were examined using these techniques in a standardized protocol at least two years after surgery. Results show excellent return of static stability and near-normal recovery of strength and endurance of quadriceps and hamstring muscles.

Adult↗
PubMed1989

Downhill walking induces rapid shallow breathing.

To examine the effect of downhill walking a form of negative work on ventilation, we studied the exercise responses of 13 healthy subjects during uphill and downhill walking on a treadmill. Each test lasted 16 min and the peak work rate was 5.6 kph with either a positive or negative 14% grade. Throughout each test we recorded VO2, VE, f, VT, HR, systolic BP and Borg's rating of perceived exertion. At the target work rates of 5.6 kph +/- 14% grade, VO2 and VE were three times greater in uphill compared with downhill walking. However, in downhill walking, f was greater compared with uphill walking wherein VT approximated baseline values, reflecting rapid shallow breathing, and VT appeared to increase after reaching some critically-low level. These trends persisted when VO2 was held constant (p less than 0.01). HR and systolic BP increased and decreased with the positive and negative grade respectively. At a constant VO2 however, HR was significantly higher during downhill compared with horizontal walking (p less than 0.01) whereas systolic BP was not significantly different (p greater than 0.05). We conclude that there is a significant difference in the ventilatory responses between the two types of work performed on a treadmill. Specifically, downhill walking is associated with rapid shallow breathing which may be countered by a protective feedback mechanism at critically-low levels of VT.

Adult↗
PubMed1989

Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity.

Benzimidazole anti-microtubule drugs, such as benomyl, induce paralysis and slow the growth of the nematode Caenorhabditis elegans. We have identified 28 mutations in C. elegans that confer resistance to benzimidazoles. All resistant mutations map to a single locus, ben-1. Virtually all these mutations are genetically dominant. Molecular cloning and DNA sequence analysis established that ben-1 encodes a beta-tubulin. Some resistant mutants are completely deleted for the ben-1 gene. Since the deletion strains appear to be fully resistant to the drugs, the ben-1 product appears to be the only benzimidazole-sensitive beta-tubulin in C. elegans. Furthermore, since animals lacking ben-1 are viable and coordinated, the ben-1 beta-tubulin appears to be nonessential for growth and movement. The ben-1 function is likely to be redundant in the nematode genome.

Alleles↗
PubMed1989

Pathophysiology and cardiorespiratory consequences of interstitial lung disease--review and clinical implications: a special communication.

The purpose of this special communication is to review the pathophysiology of interstitial lung disease (ILD) and its cardiorespiratory consequences at rest and during exercise. Patients with ILD tend to have a resting and disproportionate exercise tachycardia; resting or exercise-induced arterial desaturation; a rapid shallow breathing pattern; and in more severe cases an increase in pulmonary arterial pressure with an associated increase in right ventricular work. Although the acute exercise responses of patients with ILD have been documented, studies on their responses to exercise training are lacking. We, therefore, discuss some of the physiologic consequences of ILD and the clinical measures available to assess these patients at rest and during exercise. We present the implications of these changes for functional ability and propose that modified endurance training is important to the patient with ILD. Potential directions for clinical research in exercise training of patients with ILD are presented.

Exercise↗