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Effects of previous grazing nutrition and management on feedlot performance of cattle.

Management strategies designed to improve grazing animal performance can influence feedlot performance and carcass traits both positively and negatively. In spite of the economic relevance of potential interactions between grazing and finishing performance, controlled experiments evaluating integrated production systems are limited in number. Effects of grazing treatments can result from, or be overshadowed by, changes in gut fill, thus making it difficult to assign precise costs to different phases of production. Published reports have considered the effects of stocking rate, duration of grazing, forage characteristics, supplementation, and growth-promoting implants on subsequent finishing performance. Improvements in cattle performance attributed to changes in stocking rate generally have been neutral to positive with respect to effects on finishing performance. Comparisons among forages have led to the suggestion that forage species may contribute to differences in gastrointestinal fill of grazing cattle, thereby influencing gain and efficiency during the subsequent finishing phase. Creep-feeding suckling calves generally has increased preweaning performance but has had relatively little influence on performance during the subsequent finishing phase. Grain supplementation of stocker cattle during the grazing period has improved grazing performance, but effects on subsequent feedlot performance have been inconsistent. Potential carryover effects from protein and mineral supplementation also have been inconclusive. Lack of congruence among studies is puzzling but may be the consequence of highly varied production systems, differences in experimental procedures, and changes in gut fill or mass of internal organs. Based on the studies reviewed, the expression or absence of compensatory growth during the finishing phase appears to be related to the nutritional quality of forages utilized in the grazing period, with higher quality forages tending to yield greater compensatory effects. The bulk of evidence with suckling cattle and stocker implants suggests that effects on subsequent finishing performance are minimal. Attention is drawn to the noticeable lack of research pertaining to integrated production systems. A more thorough understanding of the interactions among grazing nutrition and management, finishing performance, and carcass traits is needed to facilitate greater economic exploitation of these relationships.

Animal Feed↗

Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial.

OBJECTIVE: To compare the treatment potential of glucosamine sulfate (GS) and ibuprofen in patients diagnosed with temporomandibular joint (TMJ) osteoarthritis (OA). METHODS: Forty women and 5 men received either GS (500 mg tid) or ibuprofen (400 mg tid) for 90 days in a randomized double blind study. ASSESSMENT: TMJ pain with function, pain-free, and voluntary maximum mouth opening, Brief Pain Inventory (BPI) questionnaire and masticatory muscle tenderness were performed after a one week washout and at Day 90. Acetaminophen (500 mg) dispensed for breakthrough pain was counted every 30 days to Day 120. RESULTS: In total, 176 adults were interviewed, 45 (26%) qualified, 39 (87%) completed the study (21 GS, 18 ibuprofen). Four discontinued due to stomach upset (3 ibuprofen, one GS), one due to dizziness (GS), one due to inadequate pain control (ibuprofen). Within-group analysis revealed significant improvement compared to baseline of all variables in both treatment groups but no change in acetaminophen used. Fifteen GS (71%) and 11 ibuprofen (61%) improved, with positive clinical response taken as a 20% decrease in primary outcome (TMJ pain with function). The number of patients with positive clinical response was not statistically different between groups (p = 0.73). Between-group comparison revealed that patients taking GS had a significantly greater decrease in TMJ pain with function, effect of pain, and acetaminophen used between Day 90 and 120 compared with patients taking ibuprofen. CONCLUSION: GS and ibuprofen reduce pain levels in patients with TMJ degenerative joint disease. In the subgroup that met the initial efficacy criteria, GS had a significantly greater influence in reducing pain produced during function and effect of pain with daily activities. GS has a carryover effect.

Adult↗

Carryover and the two-period crossover clinical trial.

The use of the two-period crossover trial for comparing two noncurative treatments in patients with a chronic disease is appealing since it eliminates the between-subject variability. However, the possibility of the existence of carryover effect leads many authors to advise that a parallel design be used whenever carryover is suspected. We examine this advice and quantify the degree of carryover required to make the parallel design preferable in terms of the power of the test of treatment effect and precision of the estimate of treatment difference. We conclude that in many situations this amount of carryover is substantial and unlikely to exist.

Analysis of Variance↗

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial.

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

Adolescent↗

The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women.

Results of recent clinical studies have lead to the hypothesis that isoflavones are cardioprotective. The aims of this trial were to determine the effect of supplementation with isoflavonoid phytoestrogens on plasma cholesterol concentrations and its distribution among lipoproteins and whether supplementation with isoflavones influences oxidisability of low density lipoprotein (LDL) ex vivo. Fourteen healthy premenopausal women participated in a randomised cross-over trial lasting four menstrual cycles (approximately 4 months). The subjects were asked to consume 86 mg of isoflavones daily for the duration of two menstrual cycles followed by placebo for an equivalent period, or vice versa. Venous blood samples were collected initially and at the end of the second and fourth menstrual cycles for the determination of plasma lipid concentrations and the resistance of LDL to copper-induced oxidation ex vivo. Accustomed dietary intake of isoflavones and lignans during the placebo period were 6.87+/-3.0 and 1.80+/-0.22 mg/day (mean+/-S.E.M.), respectively, and these did not change during the supplementation period. The intake of other dietary components remained constant during the trial. Supplementation resulted in a 5-fold increase in urinary isoflavone excretion (12.2+/-14.2 versus 70.1+/-10.3 micromol/24 h, placebo and isoflavone periods, respectively, P=0.0001). No changes in the oxidisability of LDL (lag time of 32.9+/-3.1 versus 30.4+/-2.9 min) or the plasma concentrations of total cholesterol (4.03+/-0.21 versus 4.11+/-0.18 mmol/l) or triacylglycerol (0.67+/-0.04 versus 0.73+/-0.06 mmol/l) were observed following supplementation. However a significant period effect (P=0.024) was observed and a trend towards a carryover effect (P=0.086) was noted for the concentration of HDL(3) cholesterol. Further studies are required to clarify the potential effect of isoflavones on HDL metabolism and the interaction with plasma steroid hormones during the menstrual cycle.

Adolescent↗

Omega-3 fatty acid supplementation in clinical and experimental lupus nephritis.

Nutrients rich in omega-3 fatty acids (fish oil and flaxseed) have the potential to abrogate inflammatory and atherosclerotic mechanisms known to be involved in the pathogenesis of vascular damage of systemic lupus erythematosus nephritis. Fish oil dietary supplementation decreases proteinuria and preserves renal morphology in the NZB/NZW, BXSB, and MRL/lpr mouse models of lupus nephritis and decreases mortality in the NZB/NZW and BXSB models. The anti-inflammatory and anti-atherosclerotic potential, coupled with the animal experimental data, encouraged us to carry out a dosing study of low (6 g) and higher (18 g) doses of fish oil (MaxEPA) therapy in human lupus nephritis. At the lower dose, the fish oil inhibited inflammatory mechanisms; at the higher dose, it altered both the inflammatory and atherosclerotic mechanisms. This led to a double-blind cross-over study of fish oil therapy in 26 patients with lupus nephritis followed for 2 years 10 weeks. The fish oil dietary supplementation had no significant effect on proteinuria, isotope glomerular filration rate, disease activity index, or steroid consumption. However, it did have a significant effect on lipid levels. The cross-over design suffered carryover effects (even with a 10-week wash-out period) and placebo effects of the olive oil, which created a risk of type II error. Our interest in omega-3 fatty acids led us to assess the effects of dietary supplementation with flaxseed. Not only is the flaxseed a major source of alpha-linolenic acid but it is also the richest natural source of lignan, a natural platelet-activating factor receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of part versus whole instructional strategies on skill acquisition and excess behavior.

The relative effectiveness of part versus whole teaching strategies for students with moderate and severe handicaps was investigated. Students were taught two functional tasks using the two methods, with outcome assessed by measures of acquisition, initiation, problem solving, and inappropriate behavior. Although trends in the data suggest the superiority of the part method for acquisition by students with the more severe handicaps, these effects were not significant. The whole method had a significant carryover effect on task preparation and termination. A significant effect of method was found for excess behavior: students taught by the part method exhibited less excess behavior than did students taught by the whole method.

Achievement↗

Best practice methods to apply to measurement of resting metabolic rate in adults: a systematic review.

Several factors may alter apparent resting metabolic rate (RMR) during measurement with indirect calorimetry. Likewise, numerous indirect calorimetry measurement protocols have been developed over the years, and the methodology employed could influence test results. As part of a larger project to determine the role of indirect calorimetry in clinical practice, a systematic review of the literature was undertaken to determine the ideal subject condition and test methodology for obtaining reliable measurement of RMR with indirect calorimetry. Food, ethanol, caffeine, and nicotine affect RMR for a variable number of hours after consumption; therefore, intake of these items must be controlled before measurement. Activities of daily living increase metabolic rate, but a short rest (< or =20 minutes) before testing is sufficient for the effect to dissipate. Moderate or vigorous physical activity has a longer carryover effect and therefore must be controlled in the hours before a measurement of RMR is attempted. Limited data were found regarding ideal ambient conditions for RMR testing. Measurement duration of 10 minutes with the first 5 minutes deleted and the remaining 5 minutes having a coefficient of variation <10% gave accurate readings of RMR. Individuals preparing for RMR measurement via indirect calorimetry should refrain from eating, consuming ethanol and nicotine, smoking, and engaging in physical activity for varying times before measurement. The test site should be physically comfortable and the individual should have 10 to 20 minutes to rest before measurement commences. A 10-minute test duration with the first 5 minutes discarded and the remaining 5 minutes having a coefficient of variation of <10% will give an accurate measure of RMR.

Adult↗

Quazepam: hypnotic efficacy and side effects.

Quazepam is a benzodiazepine hypnotic that can be useful in the adjunctive pharmacologic treatment of insomnia. It is slowly eliminated due to the long elimination half-lives of the parent compound and its two active metabolites, 2-oxoquazepam and N-desalkyl-2-oxoquazepam. This drug is recommended in doses of 15 mg for adults and 7.5 mg for geriatric patients. Sleep laboratory studies and clinical trials have shown that the 15 mg dose is quite efficacious for inducing and maintaining sleep not only with initial and short-term use but also with continued use. The 7.5 mg dose which has been studied less extensively has also been shown to be effective for inducing and maintaining sleep. There is considerable evidence of carryover effectiveness both during drug administration and after withdrawal. Thus, rebound phenomena are not observed during administration (early morning insomnia and daytime anxiety) and after withdrawal (rebound insomnia). Furthermore, certain behavioral side effects that have occurred with certain benzodiazepines (triazolam) have not been reported with quazepam. The only notable side effect seen with quazepam is a variable degree of daytime sedation, which can be minimized by intermittent use of the 15 mg dose when necessary and use of the 7.5 mg dose in the elderly. In comparison to triazolam and temazepam, quazepam is more effective with short-term use, and with continued use it maintains its efficacy in contrast to both of these drugs which show rapid development of tolerance. Most important, quazepam lacks the frequent and severe side effects increasingly reported with triazolam use or following its withdrawal.

Animals↗

Analgesic activity of floctafenine after cholecystectomy.

In a double-blind, crossover study involving 40 post-cholecystectomy patients, the analgesic activity of a new oral nonnarcotic agent, floctafenine, was compared with that of oral meperidine and oral propoxyphene. A behavioral approach to the measurement of pain relief, i.e., the measurement of pain on movement or coughing, was used in addition to the accepted subjective method. Floctafenine 200 mg was found to have analgesic activity intermediate between that of meperidine 75 mg and propoxyphene 65 mg. Patients reported the fewest side effects after floctafenine. Initial pain level was found to affect the final pain score. Effects on pain relief due to age, sex, time of the day, and carryover effects were also examined and not found to be significant.

Adolescent↗

Spuriously high serum concentrations of TSH due to the use of an automatic pipetting device.

In a clinically hyperthyroid patient a TSH-value of 0.75 mU/L was measured. Upon retesting TSH was <0.1 mU/L. The patient's sample initially had been preceded, in the pipetting device, by a grossly hypothyroid patient's sample. Analogous problems were subsequently documented in 10 cases when samples of other hyperthyroid patients were preceded by samples with modestly to markedly elevated TSH. The spurious elevation of TSH (0.12 to 1.18 vs. <0.1 mU/L) appears to be due to a carryover effect from the respective previous sample within the used automatic pipetting system. This carryover was much larger than previously suggested, and occurred unpredictably.

Artifacts↗

A two-year study on the effects of nicotine and its withdrawal on mood and sleep.

Acute administration of nicotine has beneficial effects on a variety of neurological and psychiatric disorders. The purpose of this study was to determine the long-term effects of transdermal nicotine on sleep and major depression. Under a single blind protocol study where patients initially received nicotine and then switched to placebo. Fourteen non-smoking patients with major depression (Hamilton Rating > or = 18) served as subjects. Transdermal nicotine (17.5 mg), was administered five days weekly for six months, three days weekly on month 7 and one day per week on month 8. From the 9th to the 24th month, once a week a patch without nicotine substituted the nicotine patch. Sleep and depression was assessed throughout. REM sleep latency changed from 32.6 min. to 78.2 min. at the end of the study, wakefulness decreased, slow wave sleep increased throughout the study and a transient decrease of REM sleep duration upon nicotine withdrawal was observed. Hamilton scores went from an initial mean score of 29.7 to a final score of 10.8. The results support the possible therapeutical effects of long-term transdermal nicotine on sleep and mood, with a carryover effect into the withdrawal period, even though, the conclusions should be taken with caution due to the design applied.

Administration, Cutaneous↗

A review of articular cartilage pathology and the use of glucosamine sulfate.

OBJECTIVE: To refresh the athletic trainer's knowledge of articular cartilage biomechanics, physiology, and structure and explore the role of glucosamine sulfate in treating articular cartilage pathologic conditions, including supplementation methods and clinical outcomes. DATA SOURCES: We searched MEDLINE from 1989 through 2000 and SPORT Discus from 1975 through 2000 using the following key words: glucosamine sulfate, articular cartilage, osteoarthritis, and proteoglycans. DATA SYNTHESIS: Articular cartilage functions as a wear-resistant, smooth, nearly frictionless, load-bearing surface. Glucosamine sulfate can be thought of as a building block that helps restore the proteoglycan-rich extracellular matrix and thus balance articular cartilage catabolism and anabolism. Beneficial clinical effects of glucosamine sulfate in the osteoarthritic population have been documented. However, the use of glucosamine sulfate for athletic articular cartilage injuries is unproved. CONCLUSIONS/RECOMMENDATIONS: Clinical studies indicate that glucosamine sulfate has been shown to be a safe and relatively effective treatment for osteoarthritis. However, no evidence to date supports or refutes a carryover effect to the athletic population and the injuries that occur in sport.

Journal Article↗

Simulation of genetic control of reproduction in beef cows. IV. Within-herd breeding value estimation with pasture mating.

Procedures for breeding value estimation for reproductive traits under pasture mating conditions were developed and tested using a computer simulation model of genetic control of bovine reproduction. The model generated annual calving rates (BCR) (0 or 1) and calving dates (CD) for each cow as a function of underlying genetic variation in two independent traits: single-service conception rate, which was indicative of the ability to conceive when estrus occurs, and postpartum interval (PPI) from calving to first estrus. Observed values for BCR and CD were shown to be complex, nonlinear functions of breeding values for ability to conceive (CRG) and for postpartum interval (PPIG) and of the previous CD. Effects of CRG on BCR and CD were small at high values of CRG, but these effects increased as CRG declined. Effects of PPIG on BCR and CD were small for cows that previously calved within the first 21 d of the calving season, but these effects increased for cows that calved after d 21. Previous CD had substantial nongenetic carryover effects on both BCR and CD. Unbiased estimates of CRG and PPIG could not be derived in the absence of breeding information. However, CD were reasonably highly correlated with breeding values for ability to conceive, provided information on open cows was included in the evaluation. Calving dates were only weakly associated with breeding values for PPI, in part because of the relatively short mean PPI (70 d) that was simulated.

Animals↗

Facilitative effects of the ampakine CX516 on short-term memory in rats: correlations with hippocampal neuronal activity.

In the companion article (Hampson et al., 1998), the ampakine CX516 (Cortex Pharmaceuticals) was shown to produce a marked facilitation of performance of a spatial delayed-nonmatch-to-sample (DNMS) task in rats. Injections of the drug before each daily session produced a marked and progressive improvement in performance at longer delays (>5 sec) that persisted for 7 d after drug treatment was terminated. In most animals (n = 9) the increase in performance carried over to the intervening vehicle for days, whereas in others (n = 3) the effects dissipated within the session according to the pharmacological half-life of CX516. In this article we report firing correlates of simultaneously recorded cells in the CA1 and CA3 fields of the hippocampus over the period in which DNMS performance was facilitated by CX516. Sample and Delay period firing was enhanced by 100-350% under CX516 and increased progressively over days as did DNMS performance. The firing increases were restricted to correct trials only and were largest on trials with long delays. Firing in the intertrial interval was also altered, but in a manner consistent with a previously demonstrated reduction in between-trial proactive interference by CX516. Finally, in animals in which the effects of CX516 were restricted to when the drug was actually present (i.e., no carryover effects), increased cell firing also paralleled the time course of the performance increase. Results are discussed with respect to the actions of ampakines on hippocampal cellular and synaptic processes that underlie DNMS performance.

Action Potentials↗

Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: To assess the effect of estradiol (E2) replacement therapy on cardiac structure and function in healthy postmenopausal women. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover study of 31 healthy postmenopausal female volunteer study subjects (55-65 years) using 12 weeks of micronized E2 replacement therapy (2 mg/day). Echocardiography and Doppler techniques were used to assess the cardiac effects of E2 at rest and during graded bicycle ergometry. RESULTS: Crossover analysis demonstrated no carryover effects of estrogen treatment (which increased serum E2 15-fold to 37.6 pmol/L) on the cardiac characteristics measured. Estradiol treatment did not affect measurements of systolic function, diastolic function, left ventricular mass, or pulmonary artery pressure at rest or during bicycle ergometry. Left ventricular end-diastolic volume at rest was slightly higher with E2 treatment (P = .03). However, this change was not reflected by changes in stroke volume, ejection fraction, or cardiac output. CONCLUSIONS: Estrogen replacement therapy, which results in physiologic serum concentrations, does not affect cardiac structure or function in normal postmenopausal women after 12 weeks of treatment.

Aged↗

Crossover design for the dose determination of an angiotensin converting enzyme inhibitor in hypertension.

In order to determine the dose regimen of new antihypertensive compounds, between-patient trials are usually performed. However, the combined use of a crossover design and a precise methodology to measure blood pressure (BP) and biological effects can provide relevant data with a minimal number of patients, if there is no carryover effect which invalidates the experiment. Such goals were successfully achieved with just 25 hypertensive patients who were randomly allocated in double-blind fashion every 2 weeks to a new angiotensin converting enzyme (ACE) inhibitor, benazepril [10 mg once a day (o.d.), 20 mg o.d., 10 mg twice a day (b.i.d.) and 20 mg b.i.d.], or a placebo. The mean BP fall [systolic (SBP)/diastolic (DBP), measured in mmHg] just before drug intake was significantly greater with benazepril: -14/-9 (10 mg o.d.); -15/-8.5 (20 mg o.d.); -22.5/-14 (10 mg b.i.d.), and -21/-13 (20 mg b.i.d.) in comparison with placebo (-3/-3). Mean active plasma renin (measured in pg/ml), assessed by an immunoradiometric assay based on two monoclonal antibodies, increased significantly in a dose-dependent manner, by +0.7 (placebo), +15.0 (10 mg o.d.), +23.4 (20 mg o.d.), +44.4 (10 mg b.i.d.) and +78.8 (20 mg b.i.d.), whereas plasma ACE decreased (by 67 and 78% after 10 and 20 mg o.d., respectively, and by 91-92% after 10 and 20 mg b.i.d.). In the clinical development of an antihypertensive drug, the earlier use of such within-patient studies, with the random insertion of one placebo period between the active periods, should help in the dose-response curve search.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects.

The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

Adult↗