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Biomedical subjects

M B Roberts

Publications and source records attributed to M B Roberts.

33 records · Page 2Linked to original sources

The effects of L-histidine and of specific histamine receptor agonists, on the expression of morphine tolerance and physical dependence in mice.

The effects of L-histidine, and of the specific histamine receptor agonists 2-methylhistamine and 4-methylhistamine, on the expression of morphine tolerance and physical dependence have been studied in mice. These agents were administered during the "withdrawal" phase of development. All of them significantly increased tolerance but reduced the degree of physical dependence. The effects of 2-methylhistamine, which has predominantly H1-receptor activity, were completely abolished by the prior administration of the H1-antagonist mepyramine. The H2-antagonist metiamide, on the other hand, did not alter the action of 2-methylhistamine on physical dependence, though tolerance was restored to its original level. The effects of 4-methylhistamine, which is a specific H2-receptor agonist, were inhibited by metiamide, but mepyramine was unable to reverse the actions of this agonist. The effects of L-histidine, the major precursor of brain histamine, were unaltered by mepyramine, but partially inhibited by metiamide. These experimental findings are discussed in detail, and are considered to give further support to the view that histamine is implicated in some way in the mechanisms of the "withdrawal" phase of morphine tolerance and physical dependence in mice, with H2-receptors probably playing the more important role.

Animals↗

Acute reactions to urographic contrast media.

A prospective study of 3509 consecutive patients examined by excretion urography has been conducted to assess the incidence and significance of the untoward effects of urographic contrast media. Four compounds were used in doses containing 160 to 500 mg iodine/kg body weight. Toxic effects, arm pain, and allegic reactions were assessed separately, while the remainder were classified according to the influence of each reaction on the investigation and the need for treatment. From the results and a review of the literature we conclude that when there is a clear clinical indication for excretion urography a dose of contrast medium containing up to 600 mg iodine/kg body weight should be injected rapidly. Prophylactic antihistamine treatment and pretesting should be abandoned. Special care is needed for small infants and the lederly and for patients with renal or hepatic failure, myeloma, heart disease, or a history of previous major reaction. Full resuscitation facilities must always be available.

Adolescent↗

The possible role of brain histamine and H1 and H2 receptors in the development of morphine tolerance and physical dependence in mice.

The possible role of brain histamine in the mechanisms of morphine tolerance and physical dependence is under investigation in mice. L-histidine and histamine, given during the 'withdrawal' phase, significantly increase tolerance to the analgesic effects of morphine but reduce the degree of physical dependence. Metiamide significantly inhibits tolerance but has no consistent effect on physical dependence. These results suggest that H2 receptors may be involved in the development of morphine tolerance. Mepyramine does not significantly affect tolerance, and with regard to dependence there is an effect only on body weight loss, which is increased. However, combined treatment with metiamide and mepyramine inhibits tolerance significantly more than metiamide alone; and withdrawal jumping is also reduced more significantly by combined treatment than by the separate administration of these drugs. It is suggested that brain histamine is definitely implicated in the mechanisms of the 'withdrawal' phase of morphine tolerance and physical dependence in mice, with H2 receptors probably playing the more important part.

Animals↗

An improved implantation pellet for rapid induction of morphine dependence in mice.

A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.

Animals↗

A study of the interaction of practolol with acetylcholine, histamine, serotonin and bradykinin in the guinea-pig, and with bean-sprout juice in the mouse.

1. The interactions of practolol with acetylcholine, histamine, serotonin and bradykinin were studied on the trachea and lung of the guinea-pig, an animal whose sensitivity to bronchoactive endogens is known to be similar to that of human asthmatic bronchi. 2. Practolol, like propranolol, potentiated the action of the first three agonists mentioned above, but, unlike propranolol, it did not potentiate the bronchospastic effect of bradykinin. 3. Practolol, in fact, antagonized the action of bradykinin, but this effect was unlike that produced by nonsteroidal anti-inflammatory drugs. 4. The possibility that beta-adrenoreceptor antagonists might show adverse interactions with certain foodstuffs was investigated, an is discussed. 5. It is suggested that the feasibility of the continued use of practolol (or the newer cardioselective beta-blockers) in asthmatics necessarily depends on the type of allergic reaction involved, and so it is not possible to generalize. Any drug or food that might cause a bronchospastic effect synergistically in the presence of a beta- adrenoreceptor antagonist, even a cardioselective one, should be regarded with suspicion.

Acetylcholine↗

Preliminary studies on increased naloxone potency and its relationship to morphine tolerance and dependence in mice.

1. Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced the antagonistic potency of naloxone. 2. A molecular sieve morphine pellet implanted for 24 h induced measurable tolerance, but the relative potency of naloxone was not significantly different from that observed after single-dose morphine pretreatment. The development of tolerance and increased naloxone potency do not, therefore, run parallel. 3. Naloxone-precipitated withdrawal symptoms were observed after single-dose morphine and after pellet implantation. However, molecular sieve morphine pellet implantation induced a higher degree of dependence as compared with single dose morphine pretreatment. 4. These results indicate that the rate of development of increased naloxone potency and of morphine tolerance and dependence do not run parallel. This implies that caution must be exercised in regarding increased naloxone potency as a sensitive indicator of the initiation and development of tolerance and dependence to morphine.

Analgesics↗

The effect of chlorpromazine pretreatment on the narcotic antagonistic potency of naloxone in mice.

1. Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced by the antagonistic potency of naloxone. 2. Pretreatment with chlorpromazine hydrochloride (0.5 2.0 mg/kg s.c.) potentiated the antinociceptive effect of morphine measured 4.5 h later. The antagonistic effect of naloxone was also enhanced. 3. The observed effect of chlorpromazine on naloxone potency was augmented when naloxone hydrochloride 0.2 mg/kg was administered in the pretreatment regime. 4. The enhanced naloxone potency induced by morphine pretreatment was inhibited by chlorpromazine administered 0.5 hr before the morphine pretreatment. 5. These results indicate that pretreatment with either morphine or chlorpromazine increased the antagonistic potency of naloxone. However, it appears that these two drugs act by different mechanisms.

Analgesics↗

Evaluation of motivationally tailored vs. standard self-help physical activity interventions at the workplace.

PURPOSE: This study compares the efficacy of a self-help intervention tailored to the individual's stage of motivational readiness for exercise adoption with a standard self-help exercise promotion intervention. DESIGN: Interventions were delivered at baseline and 1 month; assessments were collected at baseline and 3 months. SETTING: Eleven worksites participating in the Working Healthy Research Trial. SUBJECTS: Participants (n = 1559) were a subsample of employees at participating worksites, individually randomized to one of two treatment conditions. INTERVENTION: Printed self-help exercise promotion materials either (1) matched to the individual's stage of motivational readiness for exercise adoption (motivationally tailored), or (2) standard materials (standard). MEASURES: Measures of stage of motivational readiness for exercise and items from the 7-Day Physical Activity Recall. RESULTS: Among intervention completers (n = 903), chi-square analyses showed that, compared to the standard intervention, those receiving the motivationally tailored intervention were significantly more likely to show increases (37% vs. 27%) and less likely to show either no change (52% vs. 58%) or regression (11% vs. 15%) in stage of motivational readiness. Multivariate analyses of variance showed that changes in stage of motivational readiness were significantly associated with changes in self-reported time spent in exercise. CONCLUSIONS: This is the first prospective, randomized, controlled trial demonstrating the efficacy of a brief motivationally tailored intervention compared to a standard self-help intervention for exercise adoption. These findings appear to support treatment approaches that tailor interventions to the individual's stage of motivational readiness for exercise adoption.

Adult↗