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Biomedical subjects

A Beard

Publications and source records attributed to A Beard.

9 recordsLinked to original sources
PubMed2005

Safety, pharmacokinetics, and efficacy of (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine with efavirenz and stavudine in antiretroviral-naïve human immunodeficiency virus-infected patients.

Racivir [RCV; (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine], a 50:50 racemic mixture of the two beta nucleoside enantiomers, is currently in development for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. RCV was administered once a day orally for 14 days at doses of 200, 400, or 600 mg in combination with stavudine and efavirenz to HIV-1-infected treatment-naïve male volunteers in a phase Ib/IIa study. Six volunteers at each dose were monitored for a total of 35 days for tolerance, pharmacokinetics, and plasma HIV RNA levels. RCV in combination with stavudine and efavirenz was well tolerated at all doses tested. Pharmacokinetic parameters were dose proportional, and the maximum concentration of drug in serum at all doses exceeded the 90% effective concentration for wild-type HIV-1. Viral loads dropped as expected in all dosage groups, with mean reductions from 1.13 to 1.42 log10 by day 4 and 2.02 to 2.43 log10 by day 14. HIV RNA levels remained suppressed for more than 2 weeks in the absence of any additional therapy, with mean viral loads ranging from 2.1 to 2.6 log10 below baseline through day 28. By day 35, HIV RNA levels began to increase but still remained >1 log10 below baseline levels.

Administration, Oral↗
PubMed2001

Intermittent short courses of cyclosporine microemulsion for the long-term management of psoriasis: a 2-year cohort study.

BACKGROUND: Cyclosporine is effective in psoriasis, but long-term continuous therapy may be limited by renal impairment and hypertension. Intermittent short courses of treatment should minimize side effects and improve the risk-benefit ratio. OBJECTIVE: Our purpose was to assess the long-term efficacy and safety of intermittent short courses of the microemulsion formulation of cyclosporine (Neoral) in the management of chronic plaque psoriasis unresponsive to topical therapies. METHODS: In a multicenter open cohort study, 76 subjects were treated intermittently over a 2-year period. Patients with chronic plaque psoriasis were treated with cyclosporine until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomized into two groups. Group A stopped cyclosporine abruptly, whereas group B had the dose reduced by 1 mg/kg per day each week until cessation, which was within 4 weeks. On relapsing, patients received further courses of cyclosporine. Intermittent treatment was continued in this way for 2 years. RESULTS: There was no statistically significant difference in the percentage of time in remission during the 2-year period between patients randomized to stop cyclosporine abruptly (56.2%) and patients randomized to taper cyclosporine within 4 weeks (61.8%). The mean percentage of time that patients received treatment during the study was 40.5% for randomization group A, 46.2% for randomization group B, and 42.8% overall. The median time to relapse was 115.5 days after the first treatment course but became progressively shorter after multiple treatment courses. Mean blood pressure and serum creatinine levels did not show any clinically significant changes over time. CONCLUSIONS: This study indicates that intermittent short courses of cyclosporine are effective in patients with moderate to severe psoriasis for up to 2 years while improving the safety profile relative to continuous cyclosporine monotherapy.

Adult↗
PubMed2000

A nurse-coordinated educational initiative addressing primary care professionals' attitudes to and problem-solving in depression in older people--a pilot study.

This study assessed the feasibility and efficacy of an intervention focusing on primary care professionals' attitudes to, problem-solving in and practice relating to depression in old age before and after a nurse-implemented educational intervention. One hundred and twenty-one practices were approached, in which 297 doctors worked. Most practices did not want to be involved in this study. Evidence from previous studies and this one suggests that GPs are more amenable to interventions which are implemented by doctors rather than other health personnel. In addition, the lack of interest in this intervention may be a reflection of the therapeutic nihilism of primary care physicians regarding depression in older people. Sixteen surgeries expressed an interest in the study, of whom 14 participated in the study comprising 40 GPs. Thirty-one GPs and 24 nurses completed the baseline questionnaires. Only six GPs and no nurses returned completed questionnaires post-intervention. The only statistically significant before versus after change in the attitude questionnaire was found in 'I need more training to be able to deal effectively with depression in the elderly'. Mean scores were 0.73 and 0.47 respectively (p<0.05; 95%CI 3.2-47.1). Significant improvements post-intervention were, however, found in the answers to three questions (all p<0.05) addressing whether patients with depression complicated by or presenting with physical illness were referred appropriately and/or followed up. The results of our study do not indicate that the evaluation of nurse-led educational interventions in primary care is feasible in the field of depression in old age. The belief that all that is needed is the provision of accessible education of professionals by experts in the field to change attitudes and practice has not been reinforced. The high refusal rate suggests that such interventions are unlikely in any case to be generally acceptable.

Aged↗
PubMed1997

Endocrine and ultrasound evaluation of the response to PGF 2alpha and GnRH given at different stages of the luteal phase in cyclic ewes.

To investigate the effects of prostaglandin (PGF 2alpha) plus GnRH at different stages of the luteal phase 13 ewes received PGF 2alpha on Day 9 of the synchronized cycle, followed 36 h later by GnRH. This control regimen resulted in ovulation and normal corpus luteum (CL) function. In the next cycle, the ewes were treated simultaneously with PGF 2alpha and GnRH either on Day 4 (early, n = 7) or Day 9 (late, n = 6). Ovarian activity was monitored daily by ultrasonography, and blood samples were obtained to monitor hormonal patterns. Size of the largest follicle present when GnRH was administered was similar in all groups, but the preceding growth rate was greatest for the early group. In the 36 h after injection of PGF 2alpha, serum progesterone (P4) had declined to basal levels in the control cycles when GnRH was administered, but P4 concentrations were higher in the early group and were highest in the late group when the GnRH was administered with PGF 2alpha. The LH surges induced by GnRH were highest in the control cycles, and were lower in the 2 treated groups. In the early group, 6 of 7 ewes demonstrated ovulation within 48 h of GnRH, resulting in the formation of normal CL. In the late group, ovulation was delayed for about 5 d in 4 of 6 ewes, and subsequent luteal function was normal; no ovulation was detected in the other 2 ewes of this group, but the follicles became luteinized, resulting in a normal P4 profile in one and subnormal in the other. These results suggest that follicles present during the early luteal phase are capable of ovulating and forming fully functional CL in response to exogenous GnRH. In contrast, follicles present during the late luteal phase fail to ovulate in response to GnRH while P4 levels are high, even though the LH stimulus is adequate; however, these follicles persist and subsequently ovulate after P4 levels have decreased. Therefore, the endocrine milieu to which a follicle was exposed may be more important than its size in determining its ability to undergo ovulation and development into a normal CL.

Journal Article↗
PubMed1997

Concentrations of progesterone and the 5 alpha-reduced progestins, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, in luteal tissue and circulating blood and their relationship to luteal function in the African elephant, Loxodonta africana.

The 5 alpha-reduced metabolites 5 alpha-pregnane-3,20-dione (5 alpha-DHP) and 3 alpha-hydroxy-5 alpha-pregnan-20-one (5 alpha-P-3 alpha-OH) are the principal progestins biosynthesized by the African elephant corpus luteum. The aim of the present study was to determine luteal and circulating concentrations of these 5 alpha-reduced progestins in relation to progesterone (P4) and to examine whether their measurement reflects corpus luteum function. Ovarian (luteal) tissue (30 corpora lutea and 3 corpora rubra from 8 animals) and plasma samples (30 animals) were collected from pregnant and nonpregnant adult elephants shot in the Kruger National Park. Specific immunological measurement for both 5 alpha-reduced progestins and P4 was achieved by enzymeimmunoassay of tissue and plasma extracts following purification by HPLC. Mean (+/- SEM) luteal concentrations of 5 alpha-DHP and 5 alpha-P-3 alpha-OH were 79.5 +/- 9.4 micrograms/g and 196.5 +/- 24.8 micrograms/g, respectively, approximately 2-3 orders of magnitude higher than those of P4 (mean +/- SEM, 0.16 +/- 0.01 microgram/g). Whereas 5 alpha-reduced progestin concentrations tended to be lower in corpora lutea from late pregnancy compared with earlier stages and were lowest in corpora rubra, P4 levels were similar in all tissues/stages examined. The 5 alpha-reduced progestins also predominated over P4 in plasma (mean 5 alpha-DHP:P4 and 5 alpha-P-3 alpha-OH:P4 ratios 20.3 and 13.4, respectively). Similar to results for luteal tissue, plasma concentrations of 5 alpha-reduced progestins, but not of P4, were lower in late pregnancy than in earlier gestation stages and in nonpregnant animals. Moreover, plasma levels of both 5 alpha-reduced metabolites were negatively correlated with gestation age, whereas those of P4 were not. Levels of 5 alpha-reduced metabolites (without chromatography) were also measured in weekly blood samples throughout two complete ovarian cycles in one captive female. Both measurements showed a cyclic profile (similar to that of P4) with a luteal-phase elevation of 10- to 15-fold. The results indicate that 5 alpha-reduced compounds are the predominant progestins contained within and secreted by the corpus luteum of the African elephant, both during the ovarian cycle and throughout pregnancy. They also provide preliminary evidence to suggest that measurements of 5 alpha-reduced metabolites may reflect corpus luteum function more closely than those of P4.

5-alpha-Dihydroprogesterone↗
PubMed1991

An angular velocity profile in cycling derived from mechanical energy analysis.

The contributions of this article are twofold. One is procedure for determining the angular velocity profile in seated cycling that maintains the total mechanical energy of both legs constant. A five-bar linkage model (thigh, shank, foot, crank and frame) of seated (fixed hip) cycling served for the derivation of the equations to compute potential and kinetic energies of the leg segments over a complete crank cycle. With experimentally collected pedal angle data as input, these equations were used to compute the total combined mechanical energy (sum of potential and kinetic energies of the segments of both legs) for constant angular velocity pedalling at 90 rpm. Total energy varied indicating the presence of internal work. Motivated by a desire to test the hypothesis that reducing internal work in cycling will reduce energy expenditure, a procedure was developed for determining the angular velocity profile that eliminated any change in total energy. Using data recorded from five subjects, this procedure was used to determine a reference profile for an average equivalent cadence of 90 rpm. The phase of this profile is such that highest and lowest angular velocities occur when the cranks are near vertical and horizontal respectively. The second contribution is the testing of the hypothesis that the reference angular velocity profile serves to effectively reduce internal work for the subjects whose data were used to develop this profile over the range of pedalling rates (80-100 rpm) naturally preferred. In this range, the internal work was decreased a minimum of 48% relative to the internal work associated with constant angular velocity pedalling. The acceptance of this hypothesis has relevance to the protocol for future experiments which explore the effect of reduced internal work on energy expenditure in cycling.

Anthropometry↗
PubMed1990

Goniometric measurement of hip motion in cycling while standing.

The purpose of this study was to develop an instrument for quantifying the motion of the hip relative to the bicycle while cycling in the standing position. Because of the need to measure hip motion on the road as well as in the laboratory, a goniometer which locates the hip using spherical coordinates was designed. The goniometer is presented first, followed by the development of the equations that enable the distance from the joint center to the pedal spindle to be determined. The orientation of this line segment is specified by calculating two angles referenced to the frame. Also outlined are the procedures used to both calibrate the goniometer and perform an accuracy check. The results of this check indicate that the attachment point of the goniometer to the rider can be located to within 2.5 mm of the true position. The goniometer was used to record the hip movement patterns of six subjects who cycled in the standing position on a treadmill. Representative results from one test subject who cycled at 6% grade and 25 km h-1 are presented. Results indicate that the bicycle is leaned from side to side with the frequency of leaning equal to the frequency of pedalling. Extreme lean angles are +/- 6 degrees. The distance from the hip to the pedal varies approximately sinusoidally with frequency equal to pedalling rate and amplitude somewhat less than crank arm length. The absolute elevation of the hip, however, exhibits two cycles for each crank cycle. Asymmetry in the plot of elevation over a single crank cycle indicates that the pelvis rocks from side to side and that the elevation of the pelvis midpoint changes. Extreme values of the pelvis rocking angle are +/- 12 degrees. Highest pelvis midpoint elevations, however, do not occur at the same crank angles as those angles at which the pelvis rocking is extreme. It appears that the vertical motion of the hips affects pedalling mechanics when cycling in the standing position.

Anthropometry↗