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Biomedical subjects

L E Miller

Publications and source records attributed to L E Miller.

At least 19 recordsLinked to original sources

Verification of good production practices that reduce the risk of exposure of pigs to Trichinella.

Control of Trichinella infection in swine has traditionally been accomplished by inspection of individual carcasses or by post-slaughter processing to inactivate parasites. Recent declines in prevalence of this parasite in domestic swine, coupled with improvements in swine management systems, offer the opportunity to document pork safety during the production phase. We report here on a certification pilot study using an audit to document good production practices for swine relative to the risk of exposure to trichinae. Based on the results, improvements in the program have been made and further studies will be undertaken prior to launching a voluntary trichinae herd certification program in the United States.

Abattoirs↗

Context dependency in the globus pallidus internal segment during targeted arm movements.

Extracellular discharges from single neurons in the internal segment of the globus pallidus (GPi) were recorded and analyzed for rate changes associated with visually guided forearm rotations to four different targets. We sought to examine how GPi neurons contribute to movement preparation and execution. Unit discharge from 108 GPi neurons recorded in 35 electrode penetrations was aligned to the time of various behavioral events, including the onset of cued and return movements. In total, 39 of 108 GPi neurons (36%) were task-modulated, demonstrating statistically significant changes in discharge rate at various times between the presentation of visual cues and movement generation. Most often, strong modulation in discharge rate occurred selectively during either the cued (n = 32) or return (n = 2) phases of the task, although a few neurons (n = 5) were well-modulated during both movement phases. Of the 34 neurons that were modulated exclusively during cued or return movements, 50% (n = 17) were modulated similarly in association with movements to any target. The remaining 17 neurons exhibited considerable diversity in their discharge properties associated with movements to each target. Cued phases of behavior were always rewarded if executed correctly, whereas return phases were never rewarded. Overall, these data reveal that many GPi neurons discharged in a context-dependent manner, being modulated during cued, rewarded movements, but not during similar self-paced, unrewarded movements. When considered in the light of other observations, the context-dependence we have observed seems likely to be influenced by the animal's expectation of reward.

Acoustic Stimulation↗

Cytokines and hormones as possible links between endocrinosenescence and immunosenescence.

Deterioration of the immune system and the endocrine system during aging is thought to contribute to increased morbidity and mortality. Since bidirectional interrelations of both systems are present in the young and in the elderly, endocrinosenescence modulates the immune system and immunosenescence changes the endocrine system. This review focuses on age-related changes of the two systems and provides examples for the interaction of both systems during aging. It is demonstrated that both systems modulate each other in a probably unfavorable way which may be a cofactor in the aging process. Understanding of these bidirectional physiological mechanisms will help to define targets for therapeutical intervention to improve the health of aging people.

Aging↗

Modulation of IL-6 production during the menstrual cycle in vivo and in vitro.

During the menstrual cycle (MC), premenopausal women experience changes in basal temperature and their physical condition and well-being. Premenopausal female patients with chronic inflammatory diseases demonstrate changes in disease activity during the MC. The study was initiated to explore reasons for these phenomena. The sex hormone-modulated lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion in a whole blood assay, serum IL-6 concentration, and serum sex hormone concentrations were studied throughout the MC in five healthy female subjects (median, 28 years; mean, 31.2+/-2.2 years, 26-38 years). Serum IL-6 concentration demonstrated a significant increase in the luteal phase of the MC and was elevated when serum dehydroepiandrosterone (DHEA) was low and vice versa. DHEA decreased LPS-induced IL-6 secretion at six of seven time points during the MC (DHEA, p = .047). In contrast, beta-estradiol and testosterone increased LPS-induced IL-6 secretion in six of seven time points during the MC (significant for testosterone, p = .005). The study demonstrates oscillation of serum IL-6 concentration during the MC and the marked MC-dependent modulation of IL-6 secretion by sex hormones. These mechanisms may be involved in the changes in the basal temperature, the general condition, and, in patients with chronic inflammatory diseases, of disease activity during the MC.

Adult↗

Kinematic properties of rapid hand movements in a knob turning task.

In order to understand how the central nervous system controls the kinematics of rapid finger and hand movements, we studied the motions of subjects turning a knob to light-emitting diode targets, similar to tuning a radio dial. On many trials, subjects turned the knob with a single, smooth, and regular motion as revealed by the angular position and velocity trajectories, but on others, subjects produced irregularities in the kinematics. Like many past studies, we interpreted these irregularities as discrete corrective submovements. Unlike other studies, we used a direct, objective algorithm to identify overlapping submovements, detecting appreciable inflections in the acceleration traces by examining zero crossings in their derivatives, jerk and snap. The movements without overlapping submovements on average had a near symmetric, bell-shaped velocity profile that was independent of speed, and which matched the theoretical minimum jerk velocity very closely. We proposed three plausible mechanisms for altering the shape of movement kinematics, and implemented a mass-spring model with nonlinear damping to explore the possibilities. Although there was relatively little variability in the shape and symmetry of movements across trials, there was a fair amount of variability in their amplitude. We show that subjects attempted to eliminate the need for corrective submovements by making more accurate primary movements with practice, but that the variability inherent in rapid movements dictated the need for corrective submovements. Subjects used corrective submovements to improve final endpoint accuracy while reducing endpoint variability, resulting in higher task success rates.

Adult↗

Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay.

The CNS modulates immune cells by direct synaptic-like contacts in the brain and at peripheral sites, such as lymphoid organs. To study the nerve-macrophage communication, a superfusion method was used to investigate cotransmission of neuropeptide Y (NPY) with norepinephrine (NE), with interleukin (IL)-6 secretion used as the macrophage read-out parameter. Spleen tissue slices spontaneously released NE, NPY, and IL-6 leading to a superfusate concentration at 3-4 h of 1 nM:, 10 pM:, and 120 pg/ml, respectively. Under these conditions, NPY dose-dependently inhibited IL-6 secretion with a maximum effect at 10(-10) M: (p = 0.012) and 10(-9) M: (p < 0.001). Simultaneous addition of NPY at 10(-9) M: and the alpha-2-adrenergic agonist p-aminoclonidine further inhibited IL-6 secretion (p < 0.05). However, simultaneous administration of NPY at 10(-9) M: and the beta-adrenergic agonist isoproterenol at 10(-6) M: or NE at 10(-6) M: significantly increased IL-6 secretion (p < 0.005). To objectify these differential effects of NPY, electrical field stimulation of spleen slices was applied to release endogenous NPY and NE. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the NPY Y1 receptor antagonist BIBP 3226 (10(-7) M, p = 0.039; 10(-8) M, p = 0.035). This indicates that NPY increases the inhibitory effect of endogenous NE, which is mediated at low NE concentrations via alpha-adrenoceptors. Blockade of alpha-adrenoceptors attenuated electrically induced inhibition of IL-6 secretion (p < 0.001), which was dose-dependently abrogated by BIBP 3226. This indicates that under blockade of alpha-adrenoceptors endogenous NPY supports the stimulating effect of endogenous NE via beta-adrenoceptors. These experiments demonstrate the ambiguity of NPY, which functions as a cotransmitter of NE in the nerve-macrophage interplay.

Adrenergic Agonists↗

The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages.

Our objective was to investigate sympathetic and sensory nerve fibers in synovial tissue in rheumatoid arthritis (RA) and osteoarthritis (OA) in relation to histological inflammation and synovial cytokine and norepinephrine (NE) secretion. Immunohistochemistry was used to detect nerve fibers and inflammatory parameters. A superfusion technique of synovial tissue pieces was used to investigate cytokine and NE secretion. In RA, we detected 0.2 +/- 0.04 tyrosine hydroxylase-positive (TH-positive=sympathetic) nerve fibers/mm2 as compared to 4.4 +/- 0. 8 nerve fibers/mm2 in OA (P<0.001). In RA, there was a negative correlation between the number of TH-positive nerve fibers and inflammation index (RRank=-0.705, P=0.002) and synovial IL-6 secretion (RRank=-0.630, P=0.009), which was not found in OA. Substance P-positive (=sensory) nerve fibers were increased in RA as compared to OA (3.5+/-0.2 vs. 2.3+/-0.3/mm2, P=0.009). Despite lower numbers of sympathetic nerve fibers in RA than in OA, NE release was similar at baseline (RA vs. OA: 152+/-36 vs. 106+/-21 pg/ml, n.s.). Basal synovial NE secretions correlate with the number of TH-positive CD 163+ synovial macrophages (RA: RRank=0.622, P=0.031; OA: RRank=0.299, n.s.), and synovial macrophages have been shown to produce NE in vitro. Whereas sympathetic innervation is reduced, sensory innervation is increased in the synovium from patients with longstanding RA when compared to the synovium from OA patients. The differential patterns of innervation are dependent on the severity of the inflammation. However, NE secretion from the synovial tissue is maintained by synovial macrophages. This demonstrates a loss of the influence of the sympathetic nervous system on the inflammation, accompanied by an up-regulation of the sensory inputs into the joint, which may contribute to the maintenance of the disease.

Aged↗

Functional connectivity between cerebellum and primary motor cortex in the awake monkey.

Simultaneous single neuron and local field potential (LFP) recordings were made in arm-related areas of the cerebellar nuclei (CN) and primary motor cortex (M1) of two monkeys during a reaching and button pressing task. Microstimulation of focal sites in CN caused short latency (median = 3.0 ms) increases in discharge in 25% of 210 M1 neurons. Suppressive effects were less common (13%) and observed at longer latencies (median = 9.9 ms). Stimulation in CN also caused reciprocal facilitation and suppression in averages of antagonist muscle electromyograms (EMGs). The latency of these effects was approximately 8-11 ms. In contrast to the selectivity of unit and EMG effects, stimulation-evoked changes in LFP occurred over a broad range of sites. There were no significant short-latency effects detected in cross-correlation histograms between single neurons in CN and M1. However, CN spike-triggered averages of M1 LFPs were observed in a few cases (10% of 126 cases). In one-half of these, there were effects both before and after the CN spikes, which may reflect causal effects from M1 to CN, as well as from CN to M1. Overall, these results demonstrate a spatially specific, short latency, primarily excitatory pathway from CN to M1. The relatively rare effects at the single neuron level may have resulted from the difficulty in achieving optimal alignment between cerebellar and cerebral sites because of the specificity of these connections.

Action Potentials↗

A randomized prospective trial of intrarectal lidocaine for pain control during transrectal prostate biopsy: the Emory University experience.

PURPOSE: We prospectively evaluated the safety and efficacy of intrarectal lidocaine gel as anesthesia during transrectal prostate biopsy. MATERIALS AND METHODS: Of 63 consecutive men undergoing transrectal prostate biopsy 50 who qualified were enrolled in this study. Indications for the procedure were an abnormal prostate on digital rectal examination and/or elevated serum prostate specific antigen. Patients were randomized into group 1-25 who received 10 cc of 2% intrarectal lidocaine 10 minutes before the procedure and group 2-25 controls. No narcotics, sedation or analgesia was given. Pain during biopsy was assessed using a 10-point linear visual analog pain scale. RESULTS: In groups 1 and 2 median patient age was 63 and 66 years (p = 0.139), and median prostate specific antigen was 6.04 (range 1.07 to 263) and 7.24 (range 1.34 to 51.82) ng./ml. (p = 0.337). Digital rectal examination was normal and abnormal in 17 and 15 group 1, and in 8 and 10 group 2 patients, respectively. Ultrasound showed a median prostate volume of 43.6 cc (range 15.3 to 124) in group 1 and 40.3 (range 19.8 to 132) in group 2 (p = 0.710). Final histological results revealed prostate cancer in 7 men (28%) in each group. The median pain score during transrectal prostate biopsy was 2 (range 1 to 5) and 5 (range 1 to 7) in groups 1 and 2, respectively (p = 0.00001). No adverse events were noted. CONCLUSIONS: Intrarectal lidocaine gel is a simple, safe and efficacious method of providing satisfactory anesthesia in men undergoing transrectal prostate biopsy. We recommend its routine administration in all patients during this procedure.

Administration, Rectal↗

Neurotransmitter modulation of interleukin 6 (IL-6) and IL-8 secretion of synovial fibroblasts in patients with rheumatoid arthritis compared to osteoarthritis.

OBJECTIVE: The sensory nervous system with the 2 neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) is proinflammatory in experimental models of arthritis. The role of the sympathetic nervous system with norepinephrine (NE), adenosine, beta-endorphin, and methionine enkephalin (MENK) is not clearly understood. We studied the influence of these neurotransmitters on secretion of interleukin 6 (IL-6) and IL-8 in primary cultures of synovial fibroblasts of patients with rheumatoid arthritis (RA) compared to osteoarthritis (OA). METHODS: Fibroblasts were isolated using fresh synovial tissue of 5 patients with RA and 5 with OA who underwent knee joint replacement surgery. Modulation of spontaneous secretion of IL-6 and IL-8 was investigated in vitro using the neurotransmitters noted above. RESULTS: In RA fibroblasts, CGRP increased IL-6 and IL-8 secretion at 10(-10) to 10(-8) M (p at least < 0.01), which was not observed in OA fibroblasts. SP had no effect on either cytokine in RA fibroblasts but stimulated IL-8 secretion at 10(-8) M in OA fibroblasts (p < 0.01). In RA fibroblasts, adenosine and NE inhibited secretion of both cytokines at low concentrations (10(-8) M; p < 0.01). However, in OA fibroblasts there was a NE induced increase of IL-8 and IL-6 secretion at 10(-7) and 10(-6) M (p < 0.01), but no inhibition at lower concentrations (10(-8) M; p = NS). In RA fibroblasts, beta-endorphin and MENK inhibited IL-8 secretion at 10(-9) to 10(-7) M (p < 0.01), whereas in OA fibroblasts the dose response curve was shifted to lower concentrations (10(-12) M, 10(-11) M; p < 0.01). CONCLUSION: In OA fibroblasts, the sympathetic neurotransmitters were stimulatory at higher concentrations. CGRP was the most potent stimulatory neurotransmitter in RA fibroblasts whereas the sympathetic adenosine, NE, beta-endorphin, and MENK were inhibitory. This indicates a dualism of action of sympathetic and sensory neurotransmitters, with inhibitory and stimulatory effects on cytokine secretion of RA fibroblasts.

Aged↗

In vitro superfusion method to study nerve-immune cell interactions in human synovial membrane in long-standing rheumatoid arthritis or osteoarthritis.

Reports on patients with hemiparalysis indicate the importance of the nervous system for the pathophysiology of rheumatoid arthritis (RA) or osteoarthritis (OA). Norepinephrine (NE) and opioids seem to be more antiinflammatory neurotransmitters whereas substance P is proinflammatory. The study aimed to investigate the direct noradrenergic nerve-immune cell interaction in human synovial membrane. We used a recently developed superfusion technique with electrical stimulation of synovial membrane to elicit local NE from synovial membrane slices. The readout parameter of synovial immune cells was interleukin-6 (IL-6). IL-6 was spontaneously secreted from RA and OA synovial membranes. Electrical field stimulation intensively reduced IL-6 secretion. In patients with OA or RA, this electrically induced reduction of IL-6 secretion was not significantly changed by alpha- or beta-adrenergic antagonists. The study demonstrates that local endogenous NE seem to play a minor role, which may be due to a depletion of NE or loss of noradrenergic fibers during chronic RA and OA.

Aged↗

Prevalence and risk association for Trichinella infection in domestic pigs in the northeastern United States.

To determine Trichinella infection in a selected group of farm raised pigs, 4078 pigs from 156 farms in New England and New Jersey, employing various management styles, were selected based on feed type (grain, regulated waste, non-regulated waste). The number of pigs bled from each farm were based on detecting infection assuming a 0.05 prevalence rate. Serum was tested by enzyme-linked immunoassay for antibodies to Trichinella spiralis. Seropositive pigs were tested by digestion at slaughter (when possible) for the presence of Trichinella larvae. Questionnaires completed at the time of serum collection were used to develop descriptive statistics on farms tested and to determine measures of association for risk factors for the presence of Trichinella-seropositive pigs. A total of 15 seropositive pigs on 10 farms were identified, representing a prevalence rate of 0.37% and a herd prevalence rate of 6.4%. A total of nine seropositive pigs and one suspect pig from six farms were tested by digestion; four pigs (representing three farms) harbored Trichinella larvae at densities of 0.003-0.021 larvae per gram (LPG) of tissue; no larvae were found in six pigs. Risk factors which were significantly associated with seropositivity included access of pigs to live wildlife and wildlife carcasses on the farm; waste feeding had no statistically significant association with seropositivity for Trichinella infection in pigs. The presence of Trichinella infection in pigs in New England and New Jersey has declined during the past 12 years when compared with previous prevalence studies.

Animal Feed↗

Correlation of primate superior colliculus and reticular formation discharge with proximal limb muscle activity.

We studied the discharge of neurons from both the superior colliculus (SC) and the underlying mesencephalic reticular formation (MRF) and its relation to the simultaneously recorded activity of 11 arm muscles. The 242 neurons tested with a center-out reach task yielded 2,586 pairs of neuron/muscle cross-correlations (normalized, such that perfect correlations are +/-1.0). Of these, 43% had peaks with magnitude as large as 0.15, a value that corresponds to the 5% level of significance, and 16% were as large as 0.25. The great majority of peaks in this latter group was positive. The median lag time within this group was 52 ms, indicating that the neuronal discharge tended to precede the correlated muscle activity. We found a small but significantly higher proportion of cells with these relatively strong correlations in the MRF than in the SC. For both areas, these occurred most frequently with muscles of the shoulder girdle and became less frequent for axial as well as for increasingly distal arm musculature. The results support a role for the SC and MRF in guiding the arm during reach movements via the control of proximal limb musculature.

Action Potentials↗

A prospective study of transperineal prostatic block for transurethral needle ablation for benign prostatic hyperplasia: the Emory University Experience.

PURPOSE: We evaluate the feasibility, effectiveness and role of transperineal prostate block in providing anesthesia during minimally invasive radio frequency thermal therapy of the prostate. MATERIALS AND METHODS: A total of 38 consecutive patients undergoing transurethral needle ablation for symptomatic benign prostatic hyperplasia were entered in this prospective study. All patients received transperineal prostatic block as the main method of anesthesia. A mixture of equal volumes of 1% lidocaine and 0.25% bupivacaine, each with epinephrine (1:100,000 concentration ratio) was used. Pain control during the instillation of transperineal prostatic block and transurethral needle ablation was assessed using a 10-point linear analog pain scale and questionnaire. RESULTS: Median patient age was 65.5 years (range 47 to 79), with 21% of men in the eighth decade of life. Median American Urological Association symptom score was 25.0 (range 14 to 35), bother score was 20.0 (11 to 28), quality of life score was 4.0 (3 to 6) and peak urinary flow rate was 8.9 cc per second (3.5 to 15.7). Median sonographic prostate volume was 35.0 cc (range 17 to 129). Median volume of anesthetic agent used was 40.0 cc (range 30 to 60) per case (1.1 cc solution per 1 cc prostate tissue). No adverse events were encountered. Median pain score was 3.3 (range 1 to 6) during instillation of transperineal prostatic block and 1.0 (0 to 6) during transurethral needle ablation. Transperineal prostatic block proved highly effective and was a satisfactory method of anesthesia during transurethral needle ablation as judged by postoperative questionnaire. No sedation, narcotic or analgesia was required. All procedures were performed in the outpatient cystoscopy suite or office setting without support of an anesthesia team or conscious sedation monitoring. CONCLUSIONS: Transperineal prostatic block is a safe, convenient, effective and satisfactory method of minimally invasive anesthesia for transurethral needle ablation of the prostate in an outpatient office setting. Elderly patients and those at high surgical risk can be treated safely using this approach. Considerable cost saving is seen secondary to omission of charges related to anesthesia team support, recovery room facility and conscious sedation monitoring.

Aged↗

A new technique of intraprostatic fiber placement to minimize thermal injury to prostatic urothelium during indigo interstitial laser thermal therapy.

A new technique of cystoscopic insertion of laser fiber into the prostate is described for interstitial laser thermal therapy in the treatment of benign prostatic hyperplasia. The technique uses the inherent physical properties of the fused silica laser fiber with the assistance of a standard cystoscope to insert the laser fiber into the inner region of the prostate gland. Laser thermal therapy is subsequently maintained within the inner prostate at a distance from the prostatic urothelium. The technique described is simple, safe, and minimizes the potential for thermal injury to the prostatic urothelium.

Burns↗

Organization of reaching and grasping movements in the primate cerebellar nuclei as revealed by focal muscimol inactivations.

Two monkeys were trained to point to targets and to retrieve fruit bits from a Kluver board, bottles, and tubes. Once proficient in the tasks, the macaques underwent aseptic surgical implantation of a recording chamber over the cerebellar nuclei on the side of their preferred hand. After recovery from surgery, a series of mapping penetrations were completed to identify task-related areas within the cerebellar nuclei. Muscimol (4- 16 microgram; 1-2 microgram/microliter) was pressure injected at different sites within the forelimb zone, and the resultant deficits were observed as the monkeys performed the behavioral tasks. Quantitative measures of task performance were supplemented by direct observation of live and videotaped performance. The locations of nuclear inactivation sites were reconstructed from marking lesions and tracks visible in histological sections. Injections placed in the cerebellar interpositus nucleus and adjacent regions of dentate caused a variety of deficits in forelimb function. A prominent anteroposterior specialization was apparent within the forelimb zone of this intermediate nuclear region. Injections into the anterior interpositus nucleus and adjacent dentate impaired preshaping of the hand and the manipulation of objects, whereas injections placed more posteriorly in posterior interpositus nucleus and adjacent dentate produced deficits in the aiming of reach and the stability of the arm. During anterior injections, the monkeys failed to adequately extend their fingers in preparation for target contact, as documented for >85% of the reaches in the pointing task of monkey J. Up to 38% of the fruit bits it attempted to retrieve from the Kluver board were dropped. In comparison, during posterior inactivations, 15% were dropped and during control conditions 3% were dropped. The monkeys made significantly greater pointing errors during posterior inactivations (11 times for monkey J and 4 times for monkey C) than during anterior inactivations (8 times for monkey J and 2 times for monkey C). We refer to the region producing hand deficits as the anterior hand zone and the region producing reaching deficits as the posterior reach zone. These results are discussed in relation to the problem of achieving spatiotemporal coordination in the large population of nuclear cells that participate in any given movement. The results do not favor the hypothesis that coordination is achieved through a selection of Purkinje cells along beams of parallel fibers. Instead, it is proposed that distal and proximal musculature is coordinated by the adaptive influences of climbing fiber input to Purkinje cells. We envision a relatively nonspecific recruitment of anterior and posterior nuclear cells due to positive feedback in the limb premotor network, which then is shaped into an appropriate spatiotemporal pattern of discharge through the inhibitory input from Purkinje cells.

Animals↗

Primate red nucleus discharge encodes the dynamics of limb muscle activity.

We studied the dynamical relationship between magnocellular red nucleus (RNm) discharge and electromyographic (EMG) activity of 10-15 limb muscles in two monkeys during voluntary limb movement. Recordings were made from 158 neurons during two different kinds of limb movement tasks. One was a tracking task in which the subjects were required to acquire targets displayed on an oscilloscope by rotating one of six different single degree of freedom manipulanda. During this task, we recorded the angular position of the manipulandum. The monkeys also were trained in several free-form food-retrieval tasks that were much less constrained mechanically. There was generally significantly greater neuronal discharge during the free-form tasks than during the tracking task. During both types of tasks, cross-correlation and impulse response functions calculated between RNm and EMG were predominantly pulse-shaped, indicating that the dynamics of the RNm discharge were very similar to those of the muscle activity. There was no evidence during either task for a substantial dynamical transformation (e.g., integration) between the two signals as had been previously suggested. In only 15% of the cases, did these correlations have step or pulse-step dynamics. There was a relatively broad, unimodal distribution of lag times between RNm and EMG, based on the time of occurrence of the peak correlation. During tracking, the mode of this distribution was approximately 50 ms, with 80% of the lags falling between -100 and 200 ms. During the free-form task, the mode was between 0 and 20 ms, with 65% of the lags between -100 and 200 ms. A positive lag indicates that RNm discharge preceded EMG. The shape and timing of both the cross-correlation and the impulse response functions were consistent with a model in which many RNm neurons contribute mutually correlated signals which are simply summed within the spinal cord to produce a muscle activation signal.

Animals↗