Biomedical subjects

T R Scott

Publications and source records attributed to T R Scott.

At least 37 records · Page 2Linked to original sources

PubMed1999

Safety and efficacy of atovaquone and proguanil hydrochloride for the prophylaxis of Plasmodium falciparum malaria in South Africa.

The objective of this study was to determine the safety and efficacy of atovaquone and proguanil hydrochloride combination therapy for the prophylaxis of Plasmodium falciparum malaria in at-risk nonimmune subjects in South Africa. This open-label trial was conducted at research sites in South Africa during the main malaria transmission season, February through July. The study volunteers were temporarily living in, or traveling to, a malaria-endemic area. They received I tablet of 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for up to 10 weeks. Subjects were monitored using sequential clinical and laboratory assessments. Thick blood smears were stained and evaluated by a central laboratory. An immunochromatographic test for P. falciparum was also used for on-site patient management. Prophylactic success was summarized using a 95% confidence interval for the proportion of subjects who did not develop parasitemia or who withdrew due to a treatment-related adverse event. A total of 175 subjects (15% women) were enrolled in the trial. The mean duration of drug exposure was 8.9 weeks. The combination of atovaquone and proguanil hydrochloride was well tolerated. The most frequently reported adverse events considered possibly related to study treatment were headache (7%), abdominal pain (2%), increased cough (2%), and skin disorder (2%). No serious adverse events were reported, and no treatment-emergent effects were noted for any laboratory variables. One subject who was noncompliant with therapy developed parasitemia, and 3 subjects withdrew due to a treatment-related adverse event (2 subjects with headache and 1 with nausea and dizziness). The prophylaxis success rate was 97%. In this study, atovaquone and proguanil hydrochloride combination therapy had an excellent safety and efficacy profile for prophylaxis of P. falciparum malaria in nonimmune subjects.

Adult↗

PubMed1999

Gustatory neural coding in the cortex of the alert cynomolgus macaque: the quality of bitterness.

We sought to define the gustatory neural representation in primates for stimuli that humans describe as predominantly bitter. Thus we analyzed the responses of single neurons from the insular cortex of two alert, male cynomolgus macaques in response to the oral application of four basic taste stimuli (glucose, NaCl, HCl, and quinine HCl) and fruit juice, and to a series of 15 other chemicals to which humans ascribe a bitter component. Gustatory neurons occupied a volume of 109 mm3 across an area of 4.0 mm in the anterposterior plane, 4.4 mm in the mediolateral, and 6.2 mm in the dorsoventral. Taste cells represented 161 (8.6%) of the 1881 neurons tested for chemical sensitivity. Fifty of these could be monitored throughout the delivery of the entire stimulus series, and their responses constitute the data of this study. The mean spontaneous discharge rate of the cortical gustatory cells was 3.2 +/- 3.3 spikes/s (range = 0.2-17.7 spikes/s). The mean breadth-of-tuning coefficient was a moderate 0.77 +/- 0.15 (range = 0.25-0.99). Forty-eight neurons responded to taste stimuli with excitation, and two responded with inhibition. Forty-one of the 50 neurons were able to be classified into one of four functional types based on their responses to the four basic stimuli used here. These were sugar (n = 22), salt (n = 7), acid (n = 7), and quinine (n = 5). A two-dimensional space was generated from correlations among the response profiles elicited by the stimuli array. The 16 bitter chemicals formed a coherent group that was most closely related to HCl, moderately to NaCl, and bore no relationship with glucose. Within the bitter stimuli, six formed a subgroup that was most separated from all nonbitter chemicals: quinine HCl, phenlythiocarbamide, propylthiouracil, caffeine, theophylline, and phenylalanine. Humans describe these stimuli as rather purely bitter. Of the remaining 10 bitter compounds, 4 were on the fringe of the bitter group leading to NaCl: MgCl2, CaCl2, NH4Cl, and arginine. Humans characterize these as bitter-salty. Three were on the fringe leading to HCl: urea, cysteine and vitamin B1. Humans call these bitter-sour. The remaining three (nicotine, histidine, and vitamin B2) occupied the center of the bitter group. Taste quality, inferred from the position of each stimulus in the space, correlated well with human descriptions of the same stimuli, reinforcing the value of the macaque as a neural model for human gustation.

Action Potentials↗

PubMed1999

A randomized, double-blind, placebo-controlled field trial to determine the efficacy and safety of Malarone (atovaquone/proguanil) for the prophylaxis of malaria in Zambia.

Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas. A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone (250 mg of atovaquone/100 mg of proguanil hydrochloride per tablet) for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. Adult volunteers received a three-day treatment course of Malarone to eliminate pre-existing parasitemia and were then immediately randomized to treatment with either one Malarone tablet daily (n = 136), or one placebo tablet daily (n = 138) for at least 10 weeks. Malaria blood smears were prepared on a weekly basis and a failure of chemoprophylaxis was defined as any subject who had a positive blood smear, or who withdrew from the study due to a treatment-related adverse event. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively (P < 0.001). The most commonly reported adverse events with at least a possible causal relationship to study medication were headache and abdominal pain, which occurred with a higher incidence in the placebo group. No subjects were withdrawn from the study due to a treatment-related adverse event. Thus, Malarone appears to have an excellent safety and efficacy profile for the chemoprophylaxis of P. falciparum infection.

Adolescent↗

PubMed1998

Complex functional attributes of amygdaloid gustatory neurons in the rhesus monkey.

To reveal specific functions of glucose-sensitive (GS) and glucose-insensitive (GIS) cells in chemical information processing, single neuron activity was recorded in the amygdaloid body (AMY) of macaques during: 1) gustatory stimulations and 2) micro-electrophoretic administration of chemicals. Of the 629 neurons tested, 56 (8.9%) responded to, usually two or more, taste qualities. Hedonically distinct tastants usually elicited opposite firing rate changes of the gustatory cells. Seventy percent of the gustatory responses were recorded from GS neurons (17% of all AMY cells). Catecholamines (CAs) induced discharge rate changes in a majority of taste-responsive neurons: The GS gustatory cells were suppressed by norepinephrine (in the form of noradrenaline HCl, NA), whereas the GIS taste-responsive neurons were facilitated by dopamine (DA). Furthermore, NA- and/or DA-antagonists were able to attenuate or suppress taste-elicited responses of several of these cells. These and previous data indicate a specific functional organization of AMY gustatory cells: The GS and GIS taste neurons appear to be involved in differential integration of feeding-associated humoral-metabolic, motivational and exogenous chemical information.

Amygdala↗

PubMed1998

Electrophysiological responses to bitter stimuli in primate cortex.

Studies investigating fine details of gustatory coding in the domain of each basic taste quality have been completed for sweet, salt, and sour stimuli. In the present experiment, we used chemicals that humans describe as predominantly bitter. We recorded the activity of 50 taste neurons in insular cortex of two cynomolgus macaques. Stimuli were water, fruit juice, glucose, NaCl, HCl, and 16 bitter solutions. In a multidimensional taste space the 16 bitter stimuli formed a coherent cluster composed of three main subgroups: (1) QHCl, phenylalanine, theophylline, caffeine, propyl-thiouracil (PROP), and phenylthiocarbamide (PTC), all of which humans describe as rather purely bitter, (2) MgCl2, CaCl2, NH4Cl, and arginine, which humans describe as salty-bitter, and (3) urea, cysteine, and vitamin B1, which are described as sour-bitter. Vitamin B2, histidine and nicotine were in the center of the bitter cluster. Human descriptions of taste qualities conformed well to the presumed quality of each stimulus as inferred from its position in the multidimensional space (MDS), reinforcing the use of the macaque as a neural model for human gustation.

Animals↗

PubMed1998

The taste of sodium.

Sodium is crucial to physiological function. The responsibility for detecting it is assumed by the taste system, which devotes perhaps one quarter of its resources to the task. Sodium is transduced by passage into a subset of receptor cells, whose activity is relayed to the brain through a discrete gustatory channel. Responses in hindbrain, thalamus, and gustatory cortex identify the quality and concentration of sodium on the tongue. Coding of reinforcement may begin with the pons and ventral forebrain, particularly the lateral and medial hypothalamic nuclei. When body stores are sufficient, behavioral preference for sodium is mild, encompassing low concentrations and marked by weak avidity. This languid response disappears during sodium shortages. Avidity increases, and hypertonic concentrations are most preferred. This behavioral change may result from altered responsiveness in sodium-specific neurons that offer the sodium signal access to mechanisms of reinforcement. Thus, the taste system detects and recognizes sodium, and accords it a reward value commensurate with the needs of the animal.

Animals↗

PubMed1998

Efficacy and safety of atovaquone/proguanil as suppressive prophylaxis for Plasmodium falciparum malaria.

Currently recommended prophylactic regimens for Plasmodium falciparum malaria are associated with a high incidence of adverse events and/or suboptimal efficacy. In a double-blind, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of atovaquone/proguanil hydrochloride (250 mg/100 mg per tablet) to eliminate preexisting infection. Immediately thereafter, subjects were randomized to one of the three prophylactic regimens to receive one atovaquone/proguanil tablet daily (n = 68), two atovaquone/proguanil tablets daily (n = 65), or placebo (n = 65) for 10 weeks. The study endpoint for any subject was the development of parasitemia, evident on blood smear, during prophylaxis. Of the evaluable subjects, all in the low-dose (54 of 54) and high-dose (54 of 54) atovaquone/proguanil groups remained malaria-free during the 10-week prophylaxis period, in contrast to only 48% (26 of 54) in the placebo group (P < .001). Both atovaquone/proguanil prophylactic regimens were as well tolerated as placebo. Thus, atovaquone/proguanil appears to be highly efficacious and safe as prophylaxis for P. falciparum malaria.

Adolescent↗

PubMed1998

Effects of varying aeration treatment on fertilizing capacity of semen diluted with perfluorochemical emulsion and stored for twenty-four hours.

The effects of perfluorochemical (PFC) oxygen carriers in turkey semen diluents on fertility and hatchability was measured for a 10-wk period. Semen was diluted (1:1) with Beltsville Poultry Semen Extender (BPSE) or BPSE:FC-75, an emulsified mixture of BPSE and perfluorobutyltetrahydrofuran (technical grade) (FC-75) and stored for 24 h at 5 C with agitation (150 rpm) and aeration with either air, nitrogen (100%), or oxygen (100%). Sperm concentration and percentage of dead sperm were determined prior to and after storage. Sperm concentration (8.35 to 9.21 x 10(9) per milliliter) was not significantly affected by the type of diluent or aeration gas, and only stored semen diluted with BPSE: FC-75 and aerated with nitrogen had increased percentage of dead sperm. Diluent type did not affect the percentage of fertilized eggs; however, fertility and hatchability for both diluent treatments with nitrogen aeration was significantly lower (P < or = 0.05) than for the semen treatments with air or oxygen aeration. Hatchability for semen diluted with BPSE:FC-75 and aerated with oxygen (63.7%) was significantly higher (P < or = 0.05) than that for BPSE-diluted semen aerated with oxygen (43.2%). Although use of oxygen carrying fluorocarbon emulsified with BPSE did not further improve fertility when the semen was stored for 24 h while oxygenated and mechanically agitated, a beneficial effect was noted for hatchability. The fact that nitrogen severely depressed fertility confirms that the beneficial effects of agitation are due to oxygenation of the spermatozoa. Therefore, further studies of oxygen carriers in semen are warranted.

Air↗

PubMed1998

Mode of action of OB protein (leptin) on feeding.

OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56-3.5 microg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 microg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 microg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.

Animals↗

PubMed1997

Extinction of a conditioned taste aversion in rats: I. Behavioral effects.

The literature is divided over whether a conditioned taste aversion (CTA) can be fully extinguished. In Experiment 1, we created a powerful aversion in 54 rats by pairing the taste of 0.0025 M NaSaccharin (CS) with intraperitoneal injections of 127 mg/kg LiCl (US) on 3 occasions. We then offered 23-h deprived rats NaSaccharin for 10 min/day to observe the course of recovery. Extinction occurred in three phases: static, dynamic, and asymptotic. During the static phase (mean = 9.6 days), rats consumed the CS at < 10% of their preconditioned rate. With dynamic recovery (6.0 days), they increased acceptance to > 80% of preconditioning levels. Finally, they achieved asymptote (3.1 days) at 100% acceptance. In Experiment 2, we used 8 additional conditioned rats and 8 unconditioned controls. We followed the same 1-bottle extinction procedure and, again, obtained 100% acceptance. Then we offered both NaSaccharin and water for 8 days at 23 h/day and monitored lick patterns every 6 s to determine taste preferences. The conditioned animals consumed less NaSaccharin than controls on Day 1, and less NaSaccharin as a percentage of total fluid as late as Day 3. For the last 5 days of 2-bottle preference testing, there were no significant differences between the groups with regard to 1. volume of NaSaccharin or water consumed, 2. percentage of total fluid taken as NaSaccharin, 3. consumption of each fluid associated with a meal or taken spontaneously, 4. intake during the light or dark periods, or 5. the characteristics of ingestion, including number of drinking bouts, duration of bouts, number of licks/bout, and rate of licking. Therefore, a robust CTA is subject to complete behavioral extinction.

Animals↗

PubMed1997

Extinction of a conditioned taste aversion in rats: II. Neural effects in the nucleus of the solitary tract.

The formation of a conditioned taste aversion (CTA) in rats results in neural changes at several levels of the gustatory system. In the nucleus of the solitary tract (NTS), the outstanding feature of the response to a CS is a brief burst of activity that is absent in unconditioned animals. The burst occurs about 1 s after stimulus onset and is seen only in neurons that respond well to sugars and the CS (0.0025 M NaSaccharin). We recorded single neuron activity in response to 12 stimuli from taste cells in the NTS of 8 rats, in which a CTA to NaSaccharin had been created and fully extinguished, and in 8 unconditioned controls. The issue was if the neural effects of the CTA in NTS were reversed with extinction. We recorded the activity of 41 neurons in controls and 55 in CTA-extinguished rats. Responses measured across all neurons were not significantly different in spontaneous activity, breadth of tuning, overall response magnitude to each of the 12 stimuli, relationship among stimuli in taste spaces, or time-course. However, cells in the sugar-sensitive subgroup showed a clear vestige of the conditioning experience. They gave a well-defined burst of activity to the CS, though of reduced amplitude and slightly longer latency than in fully conditioned rats. This burst was no longer associated with the conditioned behavior-which was fully extinguished-though it may be a permanent marker for the once-salient CS that can influence subsequent reacquisition of the aversion.

Animals↗

PubMed1997

The monitoring of tendon tension with an implantable intratendon probe and its use in the control of neuroprostheses.

The use of a probe measuring tendon tension for the purpose of controlling a neuroprosthesis suited to spinal cord injured persons is investigated. The implanted probe detected inwardly directed radial force exerted by the tendon as the result of longitudinal tension. Varying types of load were applied to the tendon in order to measure static and dynamic parameters of the probe within the tendon. The results are discussed with respect to the potential use of the probe, within an active muscle's tendon, as a hand grasp neuroprosthesis controller. In addition, use of the probe to monitor electrically stimulated paralyzed muscle for the augmentation of closed loop control schemes is discussed.

Achilles Tendon↗

PubMed1997

Preference conditioning alters taste responses in the nucleus of the solitary tract of the rat.

Aversive conditioning has an impact on the neural signal for the gustatory conditioned stimulus (CS). Here, we determined whether the code is also affected by preference conditioning. We paired the taste of MgCl2 (CS+) with intragastric nutrients in some rats (MG), and citric acid (CS+) with nutrients in others (CI). A control group (Control) experienced both tastants without nutrients. Preferences (>90%) developed for each CS+. We recorded responses to 16 taste stimuli in the nucleus of the solitary tract. Responsiveness of acid-oriented neurons to MgCl2 in MG rats was lower than in Controls, and its profile was more distinct from those of acidic and bitter stimuli. Total activity to citric acid was unchanged in CI rats. However, its temporal profile showed a decreased phasic component, making citric acid temporally distinct from nonsugars. Therefore, the responses to both CS+ were modified, each in its own manner, to be more distinct from those of aversive stimuli. The effects of preference conditioning, however, were weaker than those of aversive conditioning.

Animals↗

PubMed1996

The effect of satiety on responses of gustatory neurons in the amygdala of alert cynomolgus macaques.

An alert cynomolgus macaque was fed a sweet solution to satiety as the activity of a gustatory neuron in the amygdala was recorded to that solution and to four other taste stimuli. This experiment was conducted a total of 14 times in two monkeys. The responses of individual neurons to the satiety stimuli were suppressed by as little as 1%, and as much as 100% by the induction of satiety (mean suppression = 58%). Nine of the 14 cells responded to the satiety solution with excitation, and their responses were suppressed by a mean of 62% by satiety. Five neurons responded with inhibition, and their responses were suppressed by a mean of 50%. Responses to other taste stimuli, not associated with satiety, were affected to a lesser extent. The amygdala is a taste relay between the primary gustatory cortex, where satiety has no influence on responses to taste stimuli, and the lateral hypothalamic area where the effect of satiety is total. The data presented here indicate that the amygdala is a functional as well as anatomical intermediary between these two areas, and serves as a stage in the process through which sensory stimuli are imbued with motivational significance.

Amygdala↗

PubMed1996

Immune cell proliferation in the harderian gland: an avian model.

Experimentation has been carried out to study proliferation of plasma cells in the chicken Harderian gland (HG) and to determine if a HG factor influences immune cell (i.e., B cell) proliferation. In young chickens, flow cytometric analysis of propidium iodide (PI)-stained plasma cells revealed that the percentages of cells in both the synthetic (S) and mitotic (G2M) phases of the cell cycle were highest between 6 and 9 weeks of age. A pattern of plasma cell depletion and repopulation in the HG was observed following administration of emetine dihydrochloride. At 3 and 5 days posttreatment the plasma cell population decreased, and by 7 days posttreatment repopulation of the gland with plasma cells occurred. This repopulation appeared as a result of plasma cell proliferation within the HG. Anti-5-bromo-2'-deoxyuridine (BrdUrd) staining of frozen sections showed that the numbers of plasma cells incorporating BrdUrd were low at 3 days posttreatment but were as high, or higher than, controls at 5 and 7 days posttreatment. These results were verified with flow cytometric data of PI-stained plasma cells. Data from bursal cell bioassays revealed proliferative activity influenced by a HG factor. Coculture of bursal cells with phorbol dibutyrate and diluted HG supernatants resulted in prolonged and increased proliferation of these cells. It is possible that the HG of chickens supports plasma cell proliferation through the elaboration of a factor which acts like a lymphokine.

Aging↗

PubMed1996

Activity in rat nucleus tractus solitarius after recovery from sodium deprivation.

Sodium depletion has powerful effects on ingestive behavior. Depleted rats consume NaCl avidly at first, but decrease their intake to normal levels as they restore their sodium balance. However, vestiges of the depletion experience are expressed as a more rapidly induced and robust sodium consumption when the rat is challenged with a second depletion. Thus, the salience of sodium to the rat is modified in a lasting manner by severe deprivation. Sodium depletion also causes changes in the responses of taste cells in the nucleus tractus solitarius (NTS). In the present study, we examined whether gustatory-evoked responses in rat NTS continue to reflect the condition induced by sodium deprivation after sodium balance is restored. Single-unit recordings were made in response to 13 taste stimuli in two groups of rats: an experimental group that underwent 10-16 days of sodium deprivation followed by a 2-week recovery period, and a control group that never experienced deprivation. Experimental animals were tested for daily intake of 0.5 M NaCl before and after deprivation; they demonstrated a clear salt appetite only on the first day of the recovery period. Electrophysiological recordings revealed no significant differences between the two groups in response to any single stimulus. Neurons from each group of rats were categorized into three subtypes: sugar-sensitive, salt-sensitive, and nonsugar cells. A comparison of responses in these three subtypes offered no significant differences across groups. Thus, as rats restore depleted sodium levels following deprivation, the responsiveness of cells in the NTS also returns to a predeprivation state.

Action Potentials↗

PubMed1996

Taste responses in the nucleus of the solitary tract in saccharin-preferring and saccharin-averse rats.

A minority of rats consistently reject the taste of sodium saccharin at concentrations that the majority find palatable. We chose rats that selected either water (WP), or 0.03 M NaSaccharin (SP) in two-bottle preference tests and monitored single unit responses to a range of taste qualities in the nucleus of the solitary tract. WP rats gave significantly greater responses to Na/Li salts and QHCl. Their responses to sugars were equal to those from SP rats. Total activity to NaSaccharin did not differ between the two groups, but its distribution across the three identified neuron types did. The response was skewed from one in which sugar (S) and sodium salt (N) participated nearly equally (SP) to one dominated by the activity of N cells and nearly devoid of an S cell contribution (WP rats). Accordingly, the response profile for NaSaccharin was correlated nearly as well with those of the sugars (+ 0.60) as with the Na/Li salts (+ 0.73) in SP rats, but was reshaped in WP rats to be nearly identical with those of the salts (+ 0.85) and unlike sugars (+ 0.30). In their heightened sensitivity to stimuli that humans call salty and bitter, and in their rejection of the complex taste of NaSaccharin, WP rats showed many of the characteristics of human tasters of PTC/PROP.

Animals↗

PubMed1996

Tri-state myoelectric control of bilateral upper extremity neuroprostheses for tetraplegic individuals.

For the purpose of bimanual control of tetraplegic hands that have useful movement restored by a neuroprosthetic device, the use of myoelectric signals from bilateral sternoclei-domastoid muscles is proposed. Three state control has been proposed where each sternocleidomastoid controls its ipsilateral hand. Demonstration was made with spinal-cord-injured and nonspinal-cord-injured subjects providing three levels of activation that can be repeatably made with each of these muscles. The agonist and antagonist sternocleidomastoids during this command control were differentiated so that the desired hand will respond to a command. Neither normal head movements nor head position within its comfortable range of motion were shown to interfere with the proposed command. The provision of feedback was shown as important to provide robustness in the operation for the users selection of the right or left hand. The performance of spinal cord injured and noninjured persons using this controller was quantitatively measured through the completion of precision tracking tasks by the manipulation of on-screen virtual hands. All subjects were able to operate the controller with a degree of skill acceptable for completion of functional tasks with bilateral stimulated hand grasps. The sensitivity of the subjects performance to variation in controller parameters was also measured.

Arm↗