Nicotine self-administration in rats is the most widely used animal model of tobacco dependence. There is increasing evidence, however, that non-nicotinic constituents in smoke contribute to addiction and that different tobacco products contain varying levels of these constituents. The present study firstly sought to compare self-administration of pure nicotine to tobacco particulate matter (TPM) to determine if there were differences in reward-efficacy attributable to the non-nicotine constituents. Secondly, cigarette and roll-your-own (RYO) TPM groups were included and compared to determine whether different formulations of non-nicotinic constituents could impact reward. Briefly, male Sprague Dawley rats were implanted with indwelling jugular catheters for self-administration (n = 76). The reinforcing efficacy of infusions of nicotine (0.0 or 30.0 μg/kg/infusion) versus cigarette/RYO TPM (with matched nicotine content) was determined using spontaneous acquisition of self-administration on a fixed ratio schedule. The progressive ratio schedule was then employed to determine the motivation to receive each drug and within-subject dose-response curves were also produced (7.5, 15.0, 30.0 and 60.0 μg/kg/infusion nicotine). The main finding was that the RYO TPM was more reinforcing and produced a different profile of reward-related behaviour compared with both the nicotine and the cigarette TPM groups. The conclusions were that non-nicotinic components have a role in tobacco dependence and that some tobacco products could have higher abuse liability, irrespective of nicotine levels.
We report the third documented case of small bowel entrapment within a sacral fracture leading to small bowel obstruction. This important diagnosis is rare and difficult to make, even with current imaging methods. We report a case in which a segment of small bowel trapped in a Denis II fracture of the sacrum required laparotomy, small bowel resection, and an omental patch over the fracture site. In this case the outcome was favorable with no residual sequelae.
SUMMARY Twenty-four patients who had undergone mitral valve surgery for pure non-rheumatic mitral regurgitation were studied non-invasively six months to six years postoperatively. The long-term results of operation were assessed on the basis of clinical history, echocardiography, and treadmill stress testing using a points scoring system. The score so obtained was used to divide the patients into those with a good response to surgery (group 1) and those responding poorly (group 2). The effects on the long-term surgical outcome of several intraoperative and preoperative factors were then analysed both together and separately.A short symptomatic history (<1 year), a normal left ventricular end-diastolic volume index (<100 ml per m2), and a large post-ectopic potentiation of KV max (>50 s-1) were found to be favourable prognostic factors when analysed independently. An angiographic ejection fraction <0 5 was uniformly associated with a poor outcome, and 71 per cent of patients in atrial fibrillation at the time of operation also responded badly. In those patients with good long-term function, cold potassium cardioplegia was more commonly used than intermittent aortic cross clamping as the means of intraoperative myocardial preservation, though this difference did not reach conventional significance.A standard analysis of variance allowed assessment of length of history, left ventricular enddiastolic volume index, and type of valve prosthesis simultaneously. This indicated that both length of history and left ventricular end-diastolic volume index were highly significant prognostic factors.The use of a Bj6rk-Shiley as opposed to a Starr-Edwards prosthesis also emerged as significantly favouring a good long-term result.The state of the left ventricular myocardium before operation and the type of valve prosthesis used were thus shown to be the prime determinants of surgical outcome in these patients. The optimum time for operation was shown to be within one year of the onset of symptoms, and before the left left ventricular end-diastolic volume index exceeds 100 ml per m2, or the ejection fraction falls to <0-5. At such a time, irreversible changes in myocardial function sufficient to negate the beneficial effects of mitral valve surgery have not yet occurred.The overall mortality and long-term functional study underwent operation. This improvement in capacity after mitral valve replacement have mortality has been the result in the main of advances improved considerably since the operation was first in intraoperative factors-principally surgical techperformed successfully in 1960
<p>Background: Animal models of drug abuse treat nicotine as the primary reinforcing agent that promotes tobacco addiction. However, rodents demonstrate poor self-administration of nicotine despite evidence of tobacco's high abuse potential in humans. This discrepancy has been attributed to other constituents of tobacco smoke that facilitate the development of nicotine dependence. Objectives: This study aimed to determine whether rats would self-administer intravenous an aqueous tobacco smoke extract (TPM) to find evidence if it was more reinforcing than nicotine alone. The study also evaluated the role of tobacco smoke constituent’s harman and norharman in any differences observed. Methods: Firstly, male Sprague-Dawley rats (n=29) were assigned to treatment groups: nicotine (30.0μg/kg/infusion), TPM (containing 30.0μg/kg/infusion nicotine) or saline vehicle. Ability for each treatment to support intravenous self-administration was assessed using spontaneous acquisition of responding on gradually increasing fixed ratio schedules (FR1, FR2, FR5). Subsequent progressive ratio (PR) testing was employed to determine reinforcing efficacy of each treatment. Then a second group of rats (N = 56) were assigned to treatment groups: nicotine alone (30.0 or 75.0μg/kg/infusion) or nicotine combined with norharman (0, 0.4, 2.5 or 6.25μg/kg/infusion) and harman (0.0, 1.6 or 10.0μg/kg, IP), and tested using a similar protocol. Results: Animals readily acquired self-administration responding for TPM and produced higher PR breakpoints (BP) than rats treated with nicotine alone or vehicle. Rats trained to respond for a larger dose of nicotine demonstrated significantly greater response rates than those receiving the lower dose of nicotine. Finally, the addition of harman and norharman to nicotine significantly reduced BP at the lower unit dose of nicotine tested. Conclusions: These findings support the hypothesis that TPM is more reinforcing than nicotine alone. However, the increased reinforcing efficacy of TPM cannot be attributed to the actions of harman and norharman. The potential role of serotonin inhibition in tobacco reward processes is discussed.</p>
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