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Biomedical subjects

J M Yeo

Publications and source records attributed to J M Yeo.

13 recordsLinked to original sources

Effects of changes in dietary amino acid balance on milk yield and mammary function in dairy cows.

Two experiments were conducted to determine whether longer-term deficiencies in the supply of limiting amino acids would be accompanied by a decline in mammary function (total DNA, cell proliferation rate and activities of key enzymes), and whether this would adversely affect the cow's ability to respond to a return to a nutritionally adequate diet. The first experiment was performed in early/mid lactation, and the second, using the same cows, was carried out in mid/late lactation. A control group of six cows were given a grass silage-cereal diet containing fish meal as the sole protein supplement (amino acid adequate) throughout the experiments, whereas another group of six cows in treatment received the control diet for 2 wk (lactation wk 5 and 6) and then were changed to a diet in which the fish meal was replaced by an equivalent amount of protein as feather meal (amino acid deficient) for 6 wk before returning to the fish meal diet for 4 wk (Experiment 1). After a rest period of 5 wk, the experimental procedure was repeated (Experiment 2). Although there was a fall in milk yield as lactation advanced, leading to lower milk yields in Experiment 2, the marked difference in milk yield between treatments was similar for the two stages of lactation (21% vs 16% in Experiment 1 and 2, respectively). In both experiments, the marked fall of milk yield in cows given the feather meal diet was completely recovered by a return to the fish meal diet. Despite the markedly lower milk yield with the amino acid-deficient diet, however, there was no clear evidence of corresponding changes in measurements of mammary function.

Amino Acids↗

Effects of amino acid nutrition on the responses of dairy cows to milking more frequently with or without injection of growth hormone.

The influence of amino acid nutrition on the response to milking more frequently, with or without injection of growth hormone, was examined in eight dairy cows in two 4 x 4 Latin squares with 28-d periods. The four treatments were a diet adequate in amino acids with or without injection of growth hormone and a diet inadequate in amino acids with or without injection of growth hormone. For all four treatments, during the last 14 d of each period, one half of the mammary gland was milked three times a day (3x), while the other half remained on twice-daily milking (2x). Both diets were based on grass silage given ad libitum and 4 kg/d of sugar beet pulp together with a supplement containing either fish meal (adequate diet) or feather meal (inadequate diet) as the only protein feeds. The diet containing feather meal is known to be deficient in His, Met, and Lys. On the fish meal diet, the cows responded positively to growth hormone and to milking more frequently and the responses to both treatments were additive. On the feather meal diet, however, even though injection of growth hormone increased the yield of milk protein by around 10%, milking more frequently did not affect milk production. It is concluded that milking more frequently has a weaker effect on the partitioning of amino acid use between body and udder than does growth hormone treatment.

Amino Acids↗

Effects of dietary amino acid balance on the response of dairy cows to an increase of milking frequency from twice to three times daily.

An experiment was conducted to examine how the response of dairy cows to a change from twice to three times-daily milking is affected by deficiencies in the dietary supplies of three amino acids, His, Met, and Lys. Six cows were used in a 6 x 6 Latin square with 14-d periods. The three dietary treatments were: grass silage and a cereal-based supplement containing feather meal as the sole protein supplement; the same silage-cereal diet supplying similar amounts of metabolizable and rumen-undegradable protein but with additional amounts of His, Met, and Lys in the form of fish meal; and the fish meal diet with additional metabolizable energy in the form of an additional 2 kg/d of sugar beet pulp. Within each of these dietary treatments, the cows were milked twice and three times daily, making a total of six treatments. When cows were given the feather meal diet, even though dietary metabolizable energy was in considerable excess, a deficiency of specific amino acids prevented any increase in milk yield in response to increasing the frequency of milking from twice to three times daily. In contrast, when cows consumed a similar level of excess metabolizable energy and a similar level of rumen-undegradable protein for which the protein was of better amino acid balance (fish meal), the increased frequency of milking led to increased yield of milk and milk protein.

Amino Acids↗

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗

Current and future trials with zidovudine.

The first placebo-controlled trial of zidovudine in the management of HIV infection involved patients with the acquired immune deficiency syndrome (AIDS) following their first episode of Pneumocystis carinii pneumonia and patients with severe AIDS-related complex (ARC). Zidovudine was shown to increase survival, and the trial was terminated early at the request of an independent review board. In order to obtain more information on the long-term efficacy and tolerance of the drug the study was continued on an open-label basis where all patients were offered zidovudine. Data from this ongoing open-label study are reviewed on a regular basis. Side-effects associated with zidovudine include anaemia and neutropenia both of which are more predominant in patients with more advanced disease. Two basic strategies have been adopted with the aim of improving the therapeutic index of the drug involving (i) dose modification and (ii) combination with other antiviral or immunomodulatory compounds. Although several phase I and II studies are proceeding it is likely that research in this area will continue to expand. AIDS patients with Kaposi's sarcoma (but without a history of AIDS-defining opportunistic infection) were precluded from the original phase II trial described above. The value of zidovudine in the treatment of the sarcoma per se has yet to be established. Trials are currently in progress in this indication evaluating the potential of zidovudine administered either alone or in combination with interferon. Possibly the largest area of research is concerned with defining the role of zidovudine earlier in the course of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

Prophylaxis against herpes labialis with acyclovir cream--a placebo-controlled study.

Patients with 6 or more recurrences per year of herpes labialis were entered into a randomized, double-blind, placebo-controlled, crossover study. During the trial, they applied acyclovir cream for 16 weeks and placebo cream for 16 weeks to all previously affected areas 4 times per day, and were subsequently observed for a further 16 weeks with no treatment. Results from the 23 evaluable cases showed that although recurrences did occur whilst on acyclovir treatment, patients suffered from significantly fewer days of disease and significantly fewer attacks of cold sores when compared with placebo.

Acyclovir↗

Oral acyclovir in the suppression of recurrent non-genital herpes simplex virus infection.

In a double-blind, placebo-controlled, cross-over trial in 11 patients suffering eight or more episodes of recurrent non-genital herpes simplex virus (HSV) infection per annum, only two patients experienced a recurrence during treatment with oral acyclovir (200 mg 4 times daily) for up to 12 weeks, compared with nine during placebo treatment (P = 0.016). Although lesion development was effectively suppressed in nine of the patients whilst taking acyclovir, the development of prodromal symptoms, and occasionally erythema, was reported by five. There was no difference between acyclovir and placebo in the time to the next recurrence following completion of treatment. No patient reported any side effects of either placebo or acyclovir therapy. It is believed that this is the first report of any form of oral therapy which is effective in suppressing recurrent non-genital HSV infection in immunocompetent patients.

Acyclovir↗

Present and future of acyclovir.

Acyclovir is now established as an effective and well tolerated therapeutic agent for the management of at least the more common infections of the herpes virus group. Evaluation of the drug nevertheless continues, primarily to verify its value in those infections caused by cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Furthermore with the development of analogues of acyclovir with better absorption profiles or enhanced anti-viral activity the future for this area of anti-viral therapy looks optimistic.

Acyclovir↗

Acyclovir: an update of the clinical applications of this antiherpes agent.

This paper reviews the clinical evaluation of acyclovir in the treatment of herpes-virus infections, predominantly those due to herpes simplex and varicella-zoster viruses. Intravenous, oral and topical acyclovir have been reported to be effective in the therapy of a wide variety of established herpes simplex virus infections and the systemic drug has been shown to be capable of suppressing reactivation of that virus. Although acyclovir has less activity against varicella-zoster virus, infections caused by this agent are also susceptible to intravenous and possibly oral therapy. Clinical efficacy against Epstein-Barr virus and cytomegalovirus infections has not been demonstrated but several studies are currently in progress. Limited evidence of in vivo activity against hepatitis B virus also requires further evaluation. Continued studies on tolerance of the drug in clinical use has confirmed the early promise of this selective antiviral, whilst initial concern about the development of widespread resistance has not been borne out in practice.

Acyclovir↗

Successful treatment of herpes labialis with topical acyclovir.

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.

Acyclovir↗

Treatment of herpes labialis.

Untreated herpes labialis may take up to 10 days or more to heal and antiviral therapy must be initiated early if it is to be effective. Acyclovir ointment has been reported to have an antiviral effect but no clinical benefit and a newer formulation, acyclovir cream, has been developed in an attempt to enhance skin penetration. In placebo-controlled trials, acyclovir cream shortened the duration of lesions significantly and when therapy was started before vesicles developed, the number of lesions aborting was increased significantly. This therapy was well tolerated by most patients. Topical acyclovir offers hope for the successful management of herpes labialis where systemic therapy is considered inappropriate.

Acyclovir↗

Acyclovir in the management of herpes labialis.

The efficacy of topical acyclovir in the treatment of herpes labialis has been evaluated in placebo-controlled trials with both the polyethylene glycol ointment and modified aqueous cream base preparations. Whereas a significant antiviral effect was demonstrated with acyclovir ointment in the two larger studies only favourable trends were demonstrated in the clinical parameters following early initiation of therapy. Significant clinical benefit was observed in a small single-centre study involving patients with frequent and generally more severe episodes of herpes labialis. In an animal model of experimental cutaneous herpes simplex virus infection acyclovir cream was found to be more effective than the ointment. This was confirmed in the first completed trial with acyclovir cream where a significant treatment effect was revealed on lesion duration and the inhibition of lesion development. Both topical preparations of acyclovir were well tolerated but acyclovir cream is to be preferred for the treatment of herpes labialis.

Acyclovir↗