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Biomedical subjects

D Murdoch

Publications and source records attributed to D Murdoch.

At least 37 records · Page 2Linked to original sources
PubMed1992

Calcipotriol. A review of its pharmacological properties and therapeutic use in psoriasis vulgaris.

Calcipotriol (calcipotriene) is a vitamin D3 analogue which inhibits epidermal cell proliferation and enhances cell differentiation. In patients with chronic plaque psoriasis involved in short term studies of 6 to 8 weeks' duration, calcipotriol ointment applied twice daily was significantly more effective than betamethasone valerate and dithranol (anthralin). Pooled data from clinical trials show that calcipotriol is well tolerated, with the majority of adverse events being mild and transient local reactions. Topically applied calcipotriol has low hypercalcaemic potential and, in contrast to topical corticosteroids, oral retinoids and orally administered calcitriol, methotrexate and cyclosporin, calcipotriol does not appear to be associated with a risk of serious adverse events. Thus, at this early stage in its clinical development, calcipotriol appears to be an effective and well tolerated topical therapy for the management of psoriasis; if promising preliminary clinical findings are confirmed, calcipotriol will represent a major advance in this difficult area of therapeutics.

Anthralin↗
PubMed1992

Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder.

Sertraline is a selective inhibitor of central serotonin reuptake. Thus, it enhances serotoninergic transmission--a property which appears to explain its antidepressant activity. Its elimination half-life (approximately 26 hours) makes it suitable for once daily administration. Although clinical experience with sertraline is limited, it appears to possess antidepressant efficacy similar to that of amitriptyline and dothiepin, marginally better than imipramine, and significantly better than placebo. Additionally, sertraline is the only antidepressant licensed in the UK for the prevention of recurrence of depression, and preliminary findings suggest that the drug may also be effective in the treatment of obsessive-compulsive disorder. Sertraline and other serotonin reuptake inhibitors possess tolerability advantages over tricyclic antidepressants. Sertraline has minimal anticholinergic activity, is essentially devoid of cardiovascular effects, has a wide therapeutic index and may be administered to elderly patients or those with underlying cardiovascular disorders. However, as with other serotonin reuptake inhibitors, sertraline has been associated with gastrointestinal disturbances (nausea, diarrhoea/loose stools) and male sexual dysfunction (primarily ejaculatory disturbance), although each of these effects is usually mild and transient, decreasing in frequency with continued treatment. As a drug class, serotonin reuptake inhibitors such as sertraline appear to provide significant advantages compared with the more established antidepressant agents, particularly in terms of tolerability. Although much broader clinical experience is required before sertraline's full therapeutic potential can be realised, if future studies confirm the encouraging initial findings, sertraline will undoubtedly become an important option in the treatment of depression.

1-Naphthylamine↗
PubMed1991

Amlodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease.

Amlodipine, a basic dihydropyridine derivative, inhibits the calcium influx through 'slow' channels in peripheral vascular and coronary smooth muscle cells, thus producing marked vasodilation in peripheral and coronary vascular beds. Short to medium term clinical trials indicate that amlodipine is effective as both an antianginal agent in patients with stable angina pectoris and an antihypertensive agent in patients with mild to moderate hypertension. In small comparative studies amlodipine was at least as effective as 'standard' agents, including atenolol, verapamil, hydrochlorothiazide or captopril in hypertension, and diltiazem or nadolol in angina pectoris. Amlodipine is well tolerated, and does not appear to cause some of the undesirable effects often associated with other cardiovascular agents (e.g. adverse changes in serum lipid patterns, cardiac conduction disturbances, postural hypotension). The most common adverse effects associated with amlodipine therapy--oedema and flushing--are related to the vasodilatory action of the drug, and are generally mild to moderate in severity. Thus, amlodipine seems to provide a useful alternative to other agents currently available for the treatment of essential hypertension and chronic stable angina pectoris, with certain pharmacodynamic and tolerability properties that should be advantageous in many patients.

Amlodipine↗
PubMed1991

Sustained release nifedipine formulations. An appraisal of their current uses and prospective roles in the treatment of hypertension, ischaemic heart disease and peripheral vascular disorders.

Nifedipine antagonises influx of calcium through cell membrane slow channels, and sustained release formulations of the calcium channel blocker have been shown to be effective in the treatment of mild to moderate hypertension and both stable and variant angina pectoris. Preliminary findings also indicate that these formulations are effective in the treatment of Raynaud's phenomenon and hypertension in pregnancy, and that they reduce the frequency of ischaemic episodes in some patients with silent myocardial ischaemia. The exact mechanism of action of nifedipine in all of these disorders has not been defined. However, its potent peripheral and coronary arterial dilator properties, together with improvements in oxygen supply/demand, are of particular importance. A major goal of sustained release therapy is to permit reductions in the frequency of nifedipine administration, preferably to once daily, and thus improve patient compliance. Two new once-daily formulations--the nifedipine gastrointestinal therapeutic system (GITS) and a fixed combination capsule comprising sustained release nifedipine 20 mg and atenolol 50 mg--have exhibited marked antihypertensive efficacy. The GITS preparation has also been used effectively in the treatment of stable angina pectoris, and both formulations appear to be well tolerated. Sustained release nifedipine formulations are generally better tolerated than their conventionally formulated counterparts, particularly with regard to reflex tachycardia. Adverse effects seem to be dose related, are mainly associated with the drug's potent vasodilatory action, and include headache, flushing and dizziness. Generally, these effects are mild to moderate in severity and transient, usually diminishing with continued treatment. Thus, sustained release nifedipine formulations are useful and established cardiovascular therapeutic agents which have demonstrable efficacy in various forms of angina, mild to moderate hypertension and Raynaud's phenomenon. Further, promising results shown by the nifedipine GITS formulation, with its advantage of once daily administration suggest that it is likely to become one of the preferred nifedipine formulations for the treatment of hypertension and the various forms of angina.

Coronary Disease↗
PubMed1991

Roxatidine acetate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in peptic ulcer disease and related disorders.

Roxatidine acetate is a histamine H2-receptor antagonist which, after almost complete oral absorption (greater than 95%), is rapidly converted to its active metabolite, roxatidine, by esterases in the small intestine, plasma and liver. Roxatidine is a potent inhibitor of basal and stimulated gastric acid secretion in animals and humans and, like most other H2-receptor antagonists, has no anti-androgenic effects and does not interfere with the hepatic metabolism of other drugs. Large-scale trials have shown that roxatidine acetate 150mg per day is as effective as standard doses of cimetidine and ranitidine in the treatment of patients with duodenal or gastric ulcer, and that roxatidine acetate 75mg in the evening is likely to become a 'standard' regimen for the prevention of peptic ulcer recurrence. Preliminary data also suggest that roxatidine acetate may be useful in the treatment of reflux oesophagitis and stomal ulcer, and in the prevention of pulmonary acid aspiration. Roxatidine acetate is an H2-receptor antagonist which has been well tolerated in clinical trials. However, broader experience is required before definitive statements about tolerability relative to other H2-receptor antagonists can be made, and before the role of roxatidine acetate in the treatment of reflux oesophagitis and stomal ulcer, and the prophylaxis of acid aspiration pneumonitis, can be clearly defined.

Animals↗
PubMed1991

Atenolol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders.

Atenolol is a selective beta 1-adrenoceptor antagonist with a duration of activity of at least 24 hours. The scope of therapeutic use of the drug has been expanded and become better defined since it was first reviewed in the Journal in 1979. Atenolol is effective and generally well tolerated in patients with all grades of hypertension. Data from comparative studies show that when administered orally, atenolol reduces blood pressure to a similar extent, and in a similar proportion of patients, as usual therapeutic doses of other beta-adrenoceptor antagonists (such as acebutolol, celiprolol, betaxolol, indenolol, metoprolol, nadolol, pindolol, propranolol, tertatolol), angiotensin converting enzyme (ACE) inhibitors (e.g. captopril, enalapril and lisinopril), calcium antagonists (e.g. amlodipine, diltiazem, felodipine, isradipine, nitrendipine, nifedipine, verapamil), doxazosin, ketanserin and alpha-methyldopa. Atenolol effectively lowers blood pressure in elderly patients with hypertension and in women with hypertension associated with pregnancy, and improves objective and subjective indices in patients with stable angina pectoris. Oral atenolol is used for preventing recurrence of supraventricular arrhythmias once control is achieved by intravenous administration of atenolol. Early intervention with intravenous atenolol followed by oral maintenance therapy reduces infarct recurrence and cardiovascular mortality in patients with known or suspected myocardial infarction. There is also encouraging evidence of reduced mortality from cardiovascular disease during long term therapy with atenolol in patients with hypertension. Atenolol is well tolerated in most patients. Increases in plasma levels of both total triglycerides and very low density lipoprotein (VLDL) triglycerides have accompanied atenolol therapy although the clinical relevance, if any, of longer term metabolic effects has yet to be determined. Its low lipid solubility and limited brain penetration results in a lower incidence of central nervous system effects than that associated with propranolol. After many years of clinical usage atenolol is a well established treatment option in several areas of cardiovascular medicine such as mild to moderate hypertension and stable angina pectoris. Furthermore, it has also shown potential in the treatment of some cardiac arrhythmias and has been associated with reduced cardiovascular mortality in patients with hypertension and in patients with myocardial infarction.

Arrhythmias, Cardiac↗
PubMed1990

Unresolved grief.

Explore the source record for details and available documents.

Conflict, Psychological↗
PubMed1990

Alcohol and crimes of violence: present issues.

Current issues in alcohol-related violence are highlighted through the examination of correlational studies between alcohol and violent crime. Alcohol is associated with violent crime at a greater than chance level and at a significantly higher level than it is associated with nonviolent crime. Heavy drinking and a verbal argument usually precede the violent act and the victim is as likely as the offender to initiate the altercation. However, it is the precipitator of the altercation who is more likely to be intoxicated. Alcohol and aggression are more strongly related than expected with violent offenders demonstrating psychopathology. Marital violence appears related to alcohol independent of other marital problems. Although there exists a strong correlational relationship between alcohol and violent crime, the nature of the evidence prohibits the establishment of a causal link. In particular, methodological problems, such as a lack of appropriate comparison groups, make it difficult to draw conclusions in this area.

Alcoholic Intoxication↗
PubMed1989

Statistical considerations in the interpretation of negative carcinogenicity data.

The regulation of toxic substances present in the environment requires that carcinogens be distinguished from noncarcinogens on the strength of the available toxicological and epidemiological evidence for carcinogenicity. In this article, we consider the difficulties associated with establishing strong evidence against carcinogenicity. In particular, the ability of both animal and human studies to detect small increases in tumor occurrence rates is evaluated in statistical terms. Consideration is also given to resolving apparent conflicts between the toxicological and the epidemiological sources of data.

Animals↗
PubMed1989

Recent developments in carcinogenic risk assessment.

In this paper, recent developments in the quantitative assessment of carcinogenic risks based on toxicological and epidemiological data are reviewed. In particular, model-free approaches to low-dose risk assessment which involve only the assumption of low-dose linearity are considered. Measures of carcinogenic potency which avoid the need to extrapolate to low doses are also described. The allometric bases for converting risk estimates between species are then discussed. Pharmacokinetic models for determining the dose delivered to the target tissue are examined, and the implications of using such models in extrapolating between doses, of exposure, and species are examined. The application of these concepts in chemical and radiation carcinogenesis is illustrated by means of brief case studies of methylene chloride and Rn. Biologically motivated cancer models based on the initiation-promotion-progression theory of carcinogenesis are discussed and compared with the classical multistage model. The estimation of risks with time-dependent exposure patterns is considered, and conditions under which the use of a time-weighted average dose is appropriate are identified. Finally, the estimation of carcinogenic risks posed by exposure to complex mixtures is explored.

Animals↗
PubMed1989

A comparison of immunoblot and DNA restriction patterns in characterising methicillin-resistant isolates of Staphylococcus aureus.

The ability of EcoR1 restriction enzyme fragmentation patterns and of immunoblotting to differentiate methicillin-resistant isolates of Staphylococcus aureus were compared. All isolates examined were typable by both methods and the reproducibility of each was excellent. Immunoblotting differentiated eight types and DNA restriction patterns four. The former technique was of value in characterising methicillin-resistant isolates of S. aureus and controlling an outbreak due to them.

DNA, Bacterial↗
PubMed1988

Tissue distribution metabolism and excretion of 2,2',4,4',5-pentachlorodiphenyl ether in the rat.

The tissue distribution, metabolism and excretion of 14C-2,2',4,4',5-pentachlorodiphenyl ether (PCDE) were studied in the rat. Radioactivity was distributed in all tissues examined, with the highest concentrations being found in the fat followed by the skin, liver, kidney and muscle. Most of the radioactivity found in the tissues was due to unchanged PCDE. Decay of PCDE in the blood was fitted to a four-compartment pharmacokinetic model, and the last compartment had a half-life of 5.8 days. A total of 55% and 1.3% of an orally administered dose was excreted in feces and urine, respectively, in 7 days. More than 64% of the fecal radioactivity was due to unchanged PCDE, while hydroxylated PCDE accounted for 23%.

Animals↗
PubMed1986

Psychotrope and alcohol use by women: one or two populations?

From a telephone survey of 1,673 Montreal women, all consenting psychotrope users and randomly selected controls (N = 179) then were interviewed in their homes as to psychotropic drug and alcohol use. The results presented are based on these in-depth interviews. In the first phase of the analysis, the respondents were grouped according to whether they abstained from both alcohol and psychotropes, used alcohol alone, psychotropes alone, or both. The variables that distinguished these groups were determined by use of one-way analysis of variance. Some of these factors included age, level of education, anxiety, nervous tension, depression, subjective ratings of health, and responses to emotional upset. The second series of results involved correlation procedures to determine the covariates of alcohol and psychotrope use. Most significant of these findings were that psychotrope use was associated with anxiety, depression, and nervous tension, while alcohol use was not. Further, unlike alcohol use, psychotrope use was associated with a variety of coping techniques for dealing with emotional upset. The findings were interpreted to mean that there are two distinct populations.

Adaptation, Psychological↗
PubMed1985

Alcohol and aggression in a group interaction.

Forty-four volunteer male subjects participated in groups of four along with two experimental confederates in a group interaction after consuming either 1.32 mg/kg of 95% USP alcohol or placebo. According to a balanced-placebo design, subjects were told they were either consuming alcohol or placebo. The task of one confederate was to initiate conversation and distract subjects from monitoring their state of intoxication while the second confederate's role was to antagonize subjects at a prescribed time. Sessions were videotaped and rated for frequency of positive and negative interactions and subjects completed rating scales evaluating each other. The results failed to show an expectancy effect on any measures; however, there was an alcohol effect seen in an increase in negative interactions as well as positive interactions and a significant expectancy X alcohol interaction for negative ratings of the provocative confederate. In those groups where the manipulation matched the expectation, alcohol-told alcohol and placebo-told placebo the confederate was seen more negatively than in the mixed groups. An attributional explanation for the results is offered and the generality of the alcohol-expectancy phenomenon questioned.

Aggression↗
PubMed1984

Determining "safe" levels of exposure: safety factors or mathematical models?

The object of regulatory toxicology is to determine "safe" levels of human exposure to toxicants present in the environment. The traditional safety factor approach is compared to more recent mathematical modeling techniques, outlining the underlying assumptions and statistical properties of each procedure. Several linear extrapolation procedures are examined in detail using computer simulation, along with the impact of nonlinear kinetics on the extrapolation process.

Biotransformation↗