Advances in non-nicotine pharmacotherapy for smoking cessation

Progress in understanding the pharmacological nature of tobacco addiction, along with the modest success rates achieved by the nicotine replacement therapies, has provided the major impetus for the development of non-nicotine drugs as smoking cessation aids. This article reviews evidence from controlled trials of several non-nicotine medications for the treatment of nicotine dependence. Clonidine was the first non-nicotine medication to show efficacy for smoking cessation in multiple studies, but its effect was found to be limited at best. Positive results across several trials have been consistently demonstrated for amfebutamone (bupropion). Encouraging results have also been observed for nortriptyline and moclobemide. Studies of combined treatments using non-nicotine medications (amfebutamone, mecamylamine, oral dextrose) with nicotine replacement therapy suggest increased efficacy relative to treatments using one or the other treatment strategy alone. Thus, available evidence indicates that non-nicotine drug treatments offer a promising panoply of therapeutic strategies for the addicted smoker.     

Animal health and food safety

Foods of animal origin have an important role in a balanced diet and must be safe for human consumption. Equally important is the need for the food to be perceived as safe by the consumer. Safe food of animal origin must be free from animal pathogens that infect man and from contamination by residues. While intensive farming practices have been linked with the rise in foodborne illness in humans, it is interesting to note that the rise has continued even when there has been a shift to less intensive farm production systems. While the production of meat, milk and eggs, regardless of new technology or changes in production methods, cannot be expected to achieve zero bacterial risk, there is the need to reduce the risk and, where possible, eliminate it at the 'on the farm stage'. The current use of the terms 'farm-to-table', 'stable-to-table' and 'plough-to-plate' clearly identifies the farm as one part of the production chain which must be considered in terms of food safety.     

The effect of bupropion on nicotine craving and withdrawal

Rationale and objectives: Bupropion has demonstrated efficacy for smoking cessation. Given the importance of nicotine craving and withdrawal in the smoking cessation process, the current study examined the effects of bupropion on these parameters during smoking abstinence. Methods: During a 2-day Baseline phase with ad lib smoking, 91 non-depressed smokers (who were not trying to quit permanently) were administered measures of nicotine craving, withdrawal symptoms, and timed measures of cognitive performance five times daily. Participants were then assigned randomly to a 14-day treatment regimen with bupropion 300 mg/day, bupropion 150 mg/day, or placebo. Thereafter, the above measures were re-administered during 3 days of abstinence on a closed research ward. Results: Relative to placebo, 300 mg bupropion significantly reduced abstinence-associated increases in rated depression, difficulty concentrating, and irritability, and attenuated a decrease in positive affect. The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period. No effects were observed on craving, anxiety, restlessness, or hunger. The lack of findings on craving measures may be explained by a floor effect; except on the first day of abstinence, neither drug nor placebo groups showed much craving elevation during abstinence. Conclusions: Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms. Received: 24 February 1999 / Final version: 15 August 1999     

Combined test of anterior pituitary function in children.

A combined test of anterior pituitary function was used on 21 normal children. It shows that a comprehensive evaluation can be made of growth hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, and gonadotrophin reserve. Simultaneous assessment of those peripheral glands associated with the anterior pituitary is possible by the measurement of thyroid hormones, cortisol, and gonadal steroids. The procedure can be completed in 4 hours with minimum inconvenience and distress to the child.     

Vasoconstriction to endothelin-1 is blunted in non-insulin-dependent diabetes: a dose-response study

The haemodynamic hypothesis for the pathogenesis of diabetic microangiopathy argues that an initial increase in microvascular blood flow leads to microvascular sclerosis and disturbed autoregulation. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide that contributes to basal vascular tone. Impairment of the vasoconstrictor response to ET-1 could result in hyperperfusion and subsequent microvascular damage. The purpose of this study was to determine whether vascular responses to ET-1 are impaired in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes). Ten patients with type 2 diabetes and nine control subjects underwent brachial artery cannulation. Forearm blood flow was measured using strain-gauge venous occlusion plethysmography. ET-1 in three doses of 5, 10, and 20 pmol/min and 0.9% saline placebo was infused in a balanced double-blind randomised manner. Vascular smooth muscle function also was assessed using sodium nitroprusside. Control subjects showed vasoconstriction to ET-1 of 5 (p < 0.05), 10 (p < 0.05), and 20 pmol/min (p < 0.01). In the diabetic group, there was no significant response to ET-1 at 5 pmol/min (p > 0.05); however, significant vasoconstriction developed at 10 and 20 pmol/min (p < 0.01). There was a significant difference in response to ET-1 at 5 pmol/min between the diabetic and control groups (p < 0.05). Responses to sodium nitroprusside were similar in both groups (p > 0.05). Patients with type 2 diabetes have a blunted vasoconstrictor response to ET-1 despite preserved vascular smooth muscle function.     

Multifocal osteolysis with nephropathy

A patient with progressive osteolysis of the carpal and tarsal bones with glomerulonephritis of unusual severity is described. There was a notable absence of osteodystrophy in this and other reported cases who had chronic renal failure.     

Initiation of human parturition. III. Fetal membrane content of prostaglandin E2 and F2alpha precursor.

Unesterified arachidonic acid is the obligatory precursor of the prostaglandins (PG), PGF2alpha and PGE2. In order to ascertain whether or not the human fetal membranes could represent a storage site for prostaglandin(s) precursor, the fatty acid content of human fetal membranes was measured. Approximately 20% of the fatty acids found in fetal membranes obtained from near-term, non-laboring women was arachidonic acid, whereas only 0.4% of the fatty acids of the parietal peritoneum of the mother is arachidonic acid. A small but significant decrease in the arachidonic acid concentration was found in the fetal membranes obtained from laboring women compared to that found prior to labor. On the other hand, the concentration of palmitic acid was increased in membranes obtained during labor while no significant changes in concentration in the remaining fatty acids were observed in membranes from laboring compared to non-laboring near-term gravidas. The significance of these observations in relation to the availability of prostaglandin precursor and the initiation of human parturition is considered.     

Initiation of human parturition. II. Identification of phospholipase A2 in fetal chorioamnion and uterine decidua.

In this study, the presence of a phospholipase has been demonstrated in the human chorioamnion and uterine decidua. That the chorioamnionic enzyme is of the phospholipase A2 type was established by product identification following the incubation of the enzyme with either radioactive phosphatidylcholine or phosphatidylethanolamine. The potential relationship between the expression of the activity of this enzyme and the regulation of arachidonic acid release, prostaglandin formation, and the initiation of labor is considered.     

Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment

Sexual dysfunction is a frequently reported side effect of many antidepressants, including serotonin reuptake inhibitors. Bupropion, an antidepressant of the aminoketone class, is relatively free of adverse sexual effects. In a randomized, double-blind, multicenter trial, sustained-release bupropion (bupropion SR) and sertraline, a selective serotonin reuptake inhibitor, were found to be similarly efficacious in the treatment of outpatients with moderate to severe depression. This report describes the results of a double-blind comparison of the sexual side effect profiles of bupropion SR and sertraline. Two hundred forty-eight patients who had received a diagnosis of moderate to severe major depression were randomly assigned to receive treatment with bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Eligible patients were required to be in a stable relationship and to have normal sexual functioning. Sexual functioning was assessed by the investigator at each clinic visit using investigator-rated structured interviews. A significantly greater percentage of sertraline-treated patients (63% and 41% of men and women, respectively) developed sexual dysfunction compared with bupropion SR-treated patients (15% and 7%, respectively). Sexual dysfunction was noted as early as day 7 in sertraline-treated patients at a dose of 50 mg/day and persisted until the end of the 16-week treatment phase. Four patients, all of whom were treated with sertraline, discontinued from the study prematurely because of sexual dysfunction. Given the similar efficacy of the two drugs in treating depression, bupropion SR may be a more appropriate antidepressant choice than sertraline in patients for whom sexual dysfunction is a concern.     

Listening to patients: using verbal data in the validation of the Aberdeen Measures of Impairment,Activity Limitation and Participation Restriction (Ab-IAP)

Background  

The purpose of the study was to evaluate the validity of the self-administered Aberdeen Measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP): by investigating how participants interpret and respond to questions using the cognitive interviewing technique.