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Biomedical subjects

R A Swain

Publications and source records attributed to R A Swain.

At least 19 recordsLinked to original sources

Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat.

Plastic changes in motor cortex capillary structure and function were examined in three separate experiments in adult rats following prolonged exercise. The first two experiments employed T-two-star (T(2)*)-weighted and flow-alternating inversion recovery (FAIR) functional magnetic resonance imaging to assess chronic changes in blood volume and flow as a result of exercise. The third experiment used an antibody against the CD61 integrin expressed on developing capillaries to determine if motor cortex capillaries undergo structural modifications. In experiment 1, T(2)*-weighted images of forelimb regions of motor cortex were obtained following 30 days of either repetitive activity on a running wheel or relative inactivity. The proton signal intensity was markedly reduced in the motor cortex of exercised animals compared with that of controls. This reduction was not attributable to alterations of vascular iron levels. These results are therefore most consistent with increased capillary perfusion or blood volume of forelimb regions of motor cortex. FAIR images acquired during experiment 2 under normocapnic and hypercapnic conditions indicated that resting cerebral blood flow was not altered under normal conditions but was elevated in response to high levels of CO(2), suggesting that prolonged exercise increases the size of a capillary reserve. Finally, the immunohistological data indicated that exercise induces robust growth of capillaries (angiogenesis) within 30 days from the onset of the exercise regimen. Analysis of other regions failed to find any changes in perfusion or capillary structure suggesting that this motor activity-induced plasticity may be specific to motor cortex.These data indicate that capillary growth occurs in motor areas of the cerebral cortex as a robust adaptation to prolonged motor activity. In addition to capillary growth, the vascular system also experiences heightened flow under conditions of activation. These changes are chronic and observable even in the anesthetized animal and are measurable using noninvasive techniques.

Aging↗

Localization of protein Ser/Thr phosphatase 5 in rat brain.

Protein phosphatase 5 is a recently discovered Ser/Thr phosphatase that is structurally related to calcineurin and protein phosphatases 1 and 2. Northern blot and in situ hybridization studies have shown that protein phosphatase 5 mRNA is present at high levels in brain and is localized to discrete regions. In the present study, we used immunocytochemistry and immunoblot analyses to examine the regional and subcellular distribution of this enzyme in brain. Our work demonstrates that protein phosphatase 5 is widely expressed throughout brain, but is not uniformly distributed. The most intense staining occurred in neurons of the cerebellum, cerebral cortex, and the supraoptic nucleus of the hypothalamus. Other areas also contained immunoreactive cell bodies, including the globus pallidus, hippocampus, thalamus, lateral preoptic area of the hypothalamus, substantia nigra and other brainstem nuclei. Staining in these cells was observed primarily in perikarya and proximal processes.

Animals↗

Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination.

Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile-X patients exhibit abnormal dendritic spine lengths and shapes on parieto-occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile-X knockout mice, that have been engineered to lack the fragile-X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi-Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile-X syndrome and normal age-matched controls. Fragile-X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile-X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile-X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile-X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood.

Adult↗

Evidence for altered Fragile-X mental retardation protein expression in response to behavioral stimulation.

The Fragile-X mental retardation protein, the protein absent in Fragile-X syndrome, is synthesized near synapses upon neurotransmitter activation. Humans and mice lacking this protein exhibit abnormal dendritic spine lengths and numbers. Here we investigated Fragile-X protein levels in animals exposed to behavioral paradigms that induce neuronal morphological change. Fragile-X protein immunoreactivity was examined in visual cortices of rats reared in a complex environment for 10 or 20 days, motor cortices of rats trained on motor-skill tasks for 3 or 7 days, and either visual or motor cortices of inactive controls. Rats exposed to a complex environment for 20 days or trained for 7 days on motor-skill tasks exhibited increased Fragile-X protein immunoreactivity in visual or motor cortices, respectively. These results provide the first evidence for a behaviorally induced alteration of Fragile-X protein expression and are compatible with previous findings suggesting synaptic regulation of its expression. These results also strengthen the association of Fragile-X mental retardation protein expression with the alteration of synaptic structure.

Animals↗

Evidence for altered Fragile-X mental retardation protein expression in response to behavioral stimulation.

The Fragile-X mental retardation protein, the protein absent in Fragile-X syndrome, is synthesized near synapses upon neurotransmitter activation. Humans and mice lacking this protein exhibit abnormal dendritic spine lengths and numbers. Here we investigated Fragile-X protein levels in animals exposed to behavioral paradigms that induce neuronal morphological change. Fragile-X protein immunoreactivity was examined in visual cortices of rats reared in a complex environment for 10 or 20 days, motor cortices of rats trained on motor-skill tasks for 3 or 7 days, and either visual or motor cortices of inactive controls. Rats exposed to a complex environment for 20 days or trained for 7 days on motor-skill tasks exhibited increased Fragile-X protein immunoreactivity in visual or motor cortices, respectively. These results provide the first evidence for a behaviorally induced alteration of Fragile-X protein expression and are compatible with previous findings suggesting synaptic regulation of its expression. These results also strengthen the association of Fragile-X mental retardation protein expression with the alteration of synaptic structure.

Animals↗

Essential neuronal pathways for reflex and conditioned response initiation in an intracerebellar stimulation paradigm and the impact of unconditioned stimulus preexposure on learning rate.

It has been demonstrated previously that pairing of tone CS and intracerebellar stimulation of lobule HVI white matter as the US produces conditioning that is robust and in many ways similar to that obtained with an airpuff US. The first study in this report addressed the effect of interpositus lesions on conditioned performance in rabbits trained with white matter stimulation as the US. It was found that interpositus lesions effectively eliminated the CR irrespective of the behavioral response measured. In addition, it was shown that the interpositus lesions also abolished the UR, providing strong evidence that the effects of the electrical stimulation were confined to the cerebellum and did not require the activation of brainstem structures. The second experiment examined performance on US-alone trials of varying durations. Response initiation within 100 ms of the US onset, regardless of US duration, indicated that reflex generation could not be due to rebound excitation of the interpositus following termination of Purkinje cell inhibition of that structure but instead likely reflects orthodromic activation of interpositus neurons via climbing fiber and/or mossy fiber collaterals. The impact of US preexposure on associative conditioning in this paradigm was also determined. Animals which received only 108 US-alone trials were massively impaired during subsequent training compared to rabbits that received fewer than 12 US-alone trials.

Animals↗

Therapeutic uses of vitamin E in prevention of atherosclerosis.

UNLABELLED: The purpose of this review is to present the evidence-based pharmacotherapeutic properties of vitamin E and provide clinical recommendations for use in the arena of atherosclerosis. METHODS: A literature search was conducted from 1966 through March 1999. All usable papers were retrieved, with large, randomized, double-blinded, clinical trials and epidemiological trials receiving emphasis. RESULTS: Vitamin E, a lipid soluble vitamin, is a potent antioxidant. Several epidemiological studies have demonstrated positive relationships between vitamin E intake and the prevention of atherosclerotic heart disease; however, only one, large randomized clinical trial (The CHAOS Trial) has been conducted using more than 400 IU per day of vitamin E. Positive outcomes included a 77-percent reduction in nonfatal myocardial infarction (MI), but no corresponding reduction in mortality. Several large clinical trials are ongoing, investigating vitamin E for the prevention of atherosclerosis. Much less work has been undertaken studying vitamin E for prevention of cerebro- and peripheral vascular disease, but there appears to be promise in these areas as well. CONCLUSIONS: On the basis of the literature search, the authors recommend 400 IU or more per day of vitamin E to patients at high risk or already diagnosed with coronary artery disease. Vitamin E supplementation may also be beneficial in the prevention of cerebro- and peripheral vascular diseases.

Antioxidants↗

Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats . I. Behavioral results.

The effects of complex motor task learning on subsequent motor performance of adult rats exposed to alcohol on postnatal days 4 through 9 were studied. Male and female Long-Evans rats were assigned to one of three treatments: (1) alcohol exposure (AE) via artificial rearing to 4.5.g kg-1 day-1 of ethanol in a binge-like manner (two consecutive feedings), (2) gastrostomy control (GC) fed isocaloric milk formula via artificial rearing, and (3) suckling control (SC), where pups remained with lactating dams. After completion of the treatments, the pups were fostered back to lactating dams, and after weaning they were raised in standard cages (two-three animals per cage) until they were 6 months old. Rats from each of the postnatal treatments then spent 20 days in one of three conditions: (1) inactive condition (IC), (2) motor control condition (MC) (running on a flat oval track), or (3) rehabilitation condition (RC) (learning to traverse a set of 10 elevated obstacles). After that all the animals were tested on three tasks, sensitive to balance and coordination deficits (parallel bars, rope climbing and traversing a rotating rod). On parallel bars, both male and female rats demonstrated the same pattern of outcomes: AE-IC rats made significantly more mistakes (slips and falls) than IC rats from both control groups. After 20 days of training in the RC condition, there were no differences between AE and both SC and GC animals in their ability to perform on the parallel bars test. On rope climbing, female animals showed a similar pattern of abilities: AE-IC rats were the worst group; exercising did not significantly improve the AE rats' ability to climb, whereas the RC groups (SC, GC and AE) all performed near asymptote and there were no significant differences among three neonatal treatment groups. There was a substantial effect of the male rats' heavier body weight on climbing ability, and this may have prevented the deficits in AE rats behavior from being detected. Nevertheless, male animals from all three postnatal treatments (SC, GC and AE) were significantly better on this task after RC. Female and male rats from all three postnatal groups demonstrated significantly better performance on the rotarod task after 20 days of 'rehabilitation'. These results suggest that complex motor skill learning improves some of the motor performance deficits produced by postnatal exposure to alcohol and can potentially serve as a model for rehabilitative intervention.

Aging↗

Selective synaptic plasticity within the cerebellar cortex following complex motor skill learning.

Complex motor skill learning, but not mere motor activity, leads to an increase in synapse number within the cerebellar cortex. The present experiment used quantitative electron microscopy to determine which synapse types were altered in number. Adult female rats were allocated to either an acrobatic condition (AC), a voluntary exercise condition (VX), or an inactive condition (IC). AC animals were trained to traverse an elevated obstacle course requiring substantial motor coordination to complete. VX animals were housed with unlimited access to running wheels and IC animals received no motor training but were handled briefly each day. Results showed the AC animals to have significantly more parallel fiber to Purkinje cell synapses than both the VX and IC animals. No other synapse type was significantly altered. Thus, the learning-dependent increase in synapse number observed within the cerebellar cortex is accomplished primarily through the addition of parallel fiber synapses.

Analysis of Variance↗

Learning-dependent dendritic hypertrophy of cerebellar stellate cells: plasticity of local circuit neurons.

Recent work has shown that motor learning, but not mere motor activity, changes the morphology of Purkinje cells, the major projection neurons of the cerebellar cortex. In the present study we examined how motor skill learning affects the dendritic morphology of the stellate local circuit neurons. Adult female rats were either trained to complete a complex motor learning task or forced to traverse a flat, obstacle-free runway. Golgi impregnated stellate cells were then traced via camera lucida and their dendritic arborizations examined with a concentric ring analysis. Results showed the motor learning animals to have significantly greater stellate cell dendritic arborizations than the activity controls. Thus these local circuit neurons exhibit morphological plasticity.

Animals↗

Diagnosis, prophylaxis, and treatment of headaches in the athlete.

BACKGROUND: Headaches are a common entity in the ambulatory population. Physicians involved in sports medicine must be able to accurately diagnose headaches in athletes and whether they are exacerbated by exertion. Many medications have proven or theoretical negative effects on athletic performance. Thus, we should consider all aspects of medical management and determine which therapy is least intrusive to the athlete's performance. We planned this review because of the small number of papers available on the effects of various medications on athletic performance. METHODS: We used MEDLINE to search from 1992 to current citations, using the medical subject headings of headache, prophylaxis, treatment, review, athletes, and exercise, alone or in combination. RESULTS: Fifty-two articles were identified and deemed appropriate for inclusion in this review. CONCLUSIONS: Acute therapy for tension headaches in the athletic population is best done with nonsteroidal anti-inflammatory drugs. Prophylaxis of chronic, recurrent tension headaches is best accomplished by night-time tricyclic antidepressants (especially nortriptyline) or selective serotonin reuptake inhibitors. Acute therapy for athletes with migraines is best managed with sumatriptan or DHE 45 and prophylaxis can be accomplished with verapamil, antidepressants, or valproate. Exertional, cluster, and structural/infectious headaches are also discussed briefly.

Analgesics, Non-Narcotic↗

Do pseudoephedrine or phenylpropanolamine improve maximum oxygen uptake and time to exhaustion?

OBJECTIVE: To study the effects of over-the-counter dosages of the pure alpha 1-agonists pseudoephedrine (PSE) and phenylpropanolamine (PPA) on selected parameters of exercise performance, and to establish a range of corresponding drug levels in the urine of the athletes who use these drugs. DESIGN: Placebo-controlled, randomized, double-blinded, multiple-dose trial. SETTING: The National Institute of Fitness and Sport, the Department of Family Medicine, Indiana University, and the Sports Medicine Lab, Department of Pathology, Indiana University, Indianapolis, Indiana. PARTICIPANTS: A convenience sample of 20 male cyclists, aged 18-35, from the local cycling community. Inclusion criteria required cycling at least 50 miles a week, no chronic medical problems, and not taking any medications. Subjects were recruited by local ads and word of mouth. INTERVENTION: Patients were randomized to one of two groups of 10 subjects. Each subject in both groups performed three separate bicycle ergometer tests after ingestion of varying dosages of alpha 1-agonists. One group performed tests after receiving placebo, 0.33 mg/kg PPA, and 0.66 mg/kg PPA, whereas the other group received placebo, 1 mg/kg PSE, and 2 mg/kg PSE. A minimum 1-week washout period was required between tests. Urine for drug testing was collected 1 h before, immediately afterward, and the next morning after testing. Drug testing was performed by gas GC/MCD at a facility approved by the International Olympic Committee. MAIN OUTCOME MEASURES: Maximum oxygen uptake (VO2max), time to exhaustion, urine drug levels of PSE and PPA, peak blood pressures (BPs), peak pulse, and Borg scale (rating of perceived exertion or RPE). MAIN RESULTS: In the PPA group, the 0.33-mg/kg dose resulted in insignificant changes in peak systolic BP (+5.4 mm Hg, p = 0.260), peak diastolic BP (-1.6 mm Hg, p = 0.622), peak pulse (-2.2 beats/min, p = 0.12), peak Borg (RPE = -0.10 (p = 0.823), time to exhaustion (-16.9 s, p = 0.287), and VO2max (+0.50 ml/kg/min, p = 0.71). No significant change was noted in any study variable at the 0.66-mg/kg PPA dose, and some effects were dissimilar to the lower PPA dose effects. Peak systolic BP increased 2.8 mm Hg (p = 0.617), diastolic BP decreased 1.6 mm Hg (p = 0.634), peak pulse increased 1.4 beats/min (p = 0.504), peak Borg RPE decreased 0.80 (p = 0.210), time to exhaustion decreased 2.6 s (p = 0.861), and VO2max decreased 2.92 ml/kg/min (p = 0.14). In the 1-mg/kg PSE group, there was a significant increase in peak systolic BP (+10.6 mm Hg, p = 0.029). No significant changes occurred in peak diastolic BP (+2.4 mm Hg, p = 0.333), peak pulse (+2.2 beats/min, p = 0.306), peak RPE (+0.2, p = 0.62), time to exhaustion (+21.4 s, p = 0.289), and VO2max (+2.29 ml/kg/min, p = 0.31). In the 2-mg/kg PSE dose trial, there were insignificant changes in peak systolic BP of +2.4 mm Hg (p = 0.559), +3.8 mm Hg in peak diastolic BP (p = 0.106), +1.6 beats/min in peak pulse (p = 0.586), -0.1 in peak Borg RPE scales (p = 0.76), -10.4 s in time to exhaustion (p = 0.41), and +1.79 ml/kg/min in VO2max (p = 0.43). Urine drug levels in those subjects receiving 1 mg/kg PSE ranged from 7-55 micrograms/ml before performance and 30-128 micrograms/ ml after performance to 7-35 micrograms/ml the next morning. Levels in those receiving 2 mg/kg ranged from 5-160 micrograms/ml before performance and 44-200 micrograms/ml after performance to 8-44 micrograms/ ml the next day. In the PPA 0.33-mg/kg dose trials, the levels ranged 1-36 micrograms/ml before performance and 9-50 micrograms/ml after performance to < 1-14 micrograms/ml the next morning. In the PPA 0.66-mg/kg dose trials, the levels were 4-52 micrograms/ml before performance, 8-80 micrograms/ml after performance, and 6-74 micrograms/ml the next day. CONCLUSIONS: We found no significant differences between trials in maximum oxygen uptake (VO2max), peak or progression of Borg Scale (RPE), maximum systolic and diastolic BPs, peak pulse, or t

Adolescent↗

The role of folic acid in deficiency states and prevention of disease.

Folic acid, a water-soluble vitamin, has been used since the 1940s to treat some cases of macrocytic anemia without neurologic disease. Folate deficiency is best diagnosed with red blood cell folate levels along with macrocytosis and/or megaloblastic anemia. In addition to reversing overt deficiency, the vitamin may reduce the incidence of neural tube defects by 45% in women who receive 400 micrograms per day. It is recommended that all women of childbearing age take 400 micrograms of folate per day. Elevations in homocysteine levels, a metabolite intimately associated with folate, are also being found with increasing regularity in those with cardiovascular diseases. Homocysteine levels are reduced by folic acid administration. Therefore, there is some biologic plausibility, but not currently direct proof, for the assumption that folate supplements may prevent heart disease, stroke, and peripheral arterial disease. Controlled trials should take place before widespread food supplementation with folate is carried out on a large scale because of the possibility of outbreaks of permanent B12-related neurologic damage in those with undiagnosed pernicious anemia. However, if a patient has a premature cardiovascular event and has minimal risk factors, ordering a test to determine homocysteine level may be advisable, and if elevated, treating with folic acid supplement as long as B12 deficiency does not coexist.

Anemia, Macrocytic↗

Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus.

Stimulating electrodes were implanted in rabbit cerebellum, providing an electrical conditioned stimulus (CS) activating cortical parallel fibers and thence Purkinje and other cells, and an electrical unconditioned stimulus (US) activating underlying white matter and eliciting unconditioned responses. Paired CS-US presentations led to the development of conditioned responses, which showed extinction following CS-alone trials and reacquisition with significant savings on reinstatement of paired trials. Increased local excitability as a result of paired training (but not following unpaired stimulus presentations) was observed in cerebellar cortex, as manifested in substantial decreases in CS threshold for response elicitation in all subjects. This preparation offers a model for the study of plastic neuronal interactions within cerebellar networks critically involved in associative learning.

Animals↗

The os acromiale: another cause of impingement.

Impingement of the shoulder is a relatively common clinical entity. The os acromiale anomaly is an uncommon one (1-8%) but can be an important cause of the impingement syndrome. The most common place of nonfusion is between the meso- and meta-acromion. The key to diagnosis is a history and physical examination compatible with the impingement syndrome and appropriate radiologic studies (i.e., an axillary view or profile view or computed tomographic scan if necessary). After diagnosis, the initial treatment is conservative with rest, ice, nonsteroidal anti-inflammatory drugs (NSAIDs), injections of corticosteroids in the subacromial space, and most importantly, an appropriate rehabilitation program. If unsuccessful, treatment should be planned based on the size of the unfused fragments. Small fragments (< 4 cm) may be removed by either arthroscopic or open means. Larger fragments may require an attempt at bone grafting and fixation since their removal may result in loss of strength of the deltoid.

Acromion↗

Natural variability and diurnal fluctuations within the bacteriophage population of the rumen.

To investigate the impact of nutritional and environmental factors on bacteriophage activity in the rumen, it is first valuable to determine the extent of natural variations and fluctuations in phage populations from different animal species, and from animals located together and separately, and variation in animals over time. Differences in phage populations between sheep on different diets, between sheep and goats, and within the rumen over time were investigated by using pulsed-field gel electrophoresis and comparing total phage DNA in ruminal fluid. It was found that no two individuals had similar DNA banding patterns, even when similarly fed and penned together, indicating there is considerable individual diversity in phage populations between animals. Despite these individual differences, the quantities, but not the banding patterns, of phage DNA were similar for animals within groups but varied between groups, suggesting that nutritional factors may influence overall phage activity in the rumen. In sheep fed once daily, a distinct diurnal variation in the phage population was observed. Two hours postfeeding, total phage DNA dropped to its lowest level. The phage population then increased, reaching a maximal level 8 to 10 h postfeeding before declining over the next 4 h to reach a stable concentration for the rest of the cycle. The general trend in phage DNA concentration appeared similar to previously recorded diurnal fluctuations in ruminal bacterial populations in cattle fed once daily.

Animals↗

Iron deficiency anemia. When is parenteral therapy warranted?

Iron deficiency anemia is a common problem encountered in primary care practice. Once the diagnosis is confirmed and the possible causes are identified, replacement of iron stores is indicated. Most patients respond favorably to oral iron preparations. However, therapy with intravenous iron dextran (InFeD) may be warranted in some cases. Side effects, which are usually mild, occur in 25% of patients. Test doses of undiluted iron dextran occasionally elicit anaphylactic reactions. However, affected patients still may be successfully treated intravenously with the use of prophylactic antihistamines, corticosteroids, and histamine2 blockers. Treatment of iron deficiency anemia almost always brings symptomatic improvement.

Adult↗

Training room evaluation of chest pain in the adolescent athlete.

A physician or athletic trainer will often be faced with an athlete complaining of chest pain during or after an event. Chest pain in children and adolescents is usually of a noncardiac origin; only 5% of cases are due to cardiac problems. With a properly documented history and physical evaluation, one can usually identify the etiology of the chest discomfort or at least rule out any serious difficulties. The various diagnostic possibilities include cardiac, musculoskeletal, pulmonary, gastrointestinal, and psychiatric causes of pain. We discuss several specific conditions, as well as the signs, symptoms, and basic management.

Adolescent↗