Appropriateness of digoxin use in medical outpatients

PURPOSE: Digoxin is the third most commonly prescribed drug, yet limited information exists about its use in outpatients. Therefore, 242 medical outpatients receiving digoxin at our hospital were studied to evaluate the appropriateness of its use, defined by: (1) current or past supraventricular arrhythmias and/or (2) left ventricular systolic dysfunction (ejection fraction less than 45 percent). PATIENTS AND METHODS: Charts of 242 patients receiving digoxin were obtained. The patients were divided into groups based upon their physician's stated indication for digoxin therapy. Patients with only a clinical diagnosis of congestive heart failure (CHF) underwent echocardiography or radionuclide angiography to quantify left ventricular systolic function. Those with documented supraventricular arrhythmias and/or those with confirmed left ventricular systolic dysfunction were classified as appropriate candidates for digoxin. RESULTS: Ninety-five percent of patients received digoxin for appropriate indications; 75 percent had confirmed supraventricular arrhythmias (27 percent also had CHF) and 20 percent with normal sinus rhythm had documented systolic dysfunction. However, physicians had difficulty in the clinical assessment of left ventricular function; 18 percent of patients with sinus rhythm and CHF by the Framingham scoring system and 20 percent of those with supraventricular arrhythmias and CHF had preserved systolic function. An S3 was present in 15 percent of patients with preserved ejection fraction and CHF and in 69 percent with low ejection fraction; hypertension was significantly more common in the former group. Noninvasive assessment of systolic function was obtained in 97 percent of patients independent of this study, yet some patients without supraventricular arrhythmias and with documented preservation of systolic function continued to receive the drug. CONCLUSION: Noninvasive assessment of left ventricular function, which appears to have become routine, is of value in the appropriate utilization of digoxin, since clinicians' assessment of left ventricular function may be inaccurate. Physicians also do not always discontinue digoxin therapy when indicated.     

Hyperaemia in rat neocortex produced by acute exposure to methylenedioxymethamphetamine

Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [¹⁴C]iodoantipyrine and [¹⁴C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.     

Evaluation of the effects of opioid agonists and antagonists under a delayed matching-to-sample procedure in pigeons

The effects of several opioid agonists and antagonists were examined in pigeons performing under a delayed matching-to-sample procedure. The mu agonists morphine and l-methadone, the kappa agonists U 50,488 and ethylketocyclazocine, and the opioid antagonist naloxone had no effect on the accuracy of responding. These drugs were, however, behaviorally active as evidenced by the dose-dependent decreases in rates of responding associated with their administration. In contrast, the sigma agonists (+) N-allylnormetazocine and phencyclidine decreased the accuracy of responding in a dose-dependent fashion. The relative magnitude of these drug-induced decreases in accuracy were similar across the no delay (0-s), short (2-s), and long (8-s) delay intervals. For these drugs, accuracy-decreasing effects were obtained only at doses that reduced rates of responding. The results of the present investigation parallel those reported in pigeons responding under drug discrimination tasks, in which the discriminative stimulus properties produced by the mu and kappa agonists are similar to each other but distinguishable from those produced by the sigma agonists.Recipient of Research Scientist Development Award DA 00033 from the National Institute on Drug Abuse     

Lead accumulation in the bones of aging male mice.

The lead content of mouse femurs increased by 83% between 76 and 958 days of age with values ranging from 0.192 to 1.78 ng Pb/mg dry weight. These values are remarkably lower than in previous reports for the lead content of bone. The lead content of mouse liver showed no aging-related trend with values ranging from 0.00823 to 0.0149 ng/mg dry weight. Bone density, calcium and collagen content were not related to the lead content. We conclude that while bone lead content is very low in mice, it increases with aging but does not appear to be related to the osteopenia which develops in the C57BL/6J male mouse.     

Topical high-molecular-weight hyaluronan and a roofing barrier sheet equally inhibit postlaminectomy fibrosis.

BACKGROUND CONTEXT: The relevance of epidural fibrosis to failed back surgical outcomes remains controversial. Previous studies on the correlation between epidural fibrosis and clinical outcome after laminectomy are inconclusive, and clinical approaches applied to reduce postlaminectomy spinal canal scarring have produced mixed outcomes. PURPOSE: Improved preclinical models are required to address the fundamental question of the relationship between postlaminectomy fibrosis and chronic pain. This study is directed at establishing small animal postlaminectomy models characterized by significantly reduced scar within the spinal canal postoperatively. Such preclinical models are offered as a platform for future studies to explore the potential relationship between postlaminectomy epidural fibrosis and persistent neuropathy with its potential for altered spinal mechanisms for pain processing, so-called spinal facilitation. Such experiments could be constructed in these models for comparison of pain behavior and its underlying neurochemistry both in the presence and absence of extensive postlaminectomy epidural scar. STUDY DESIGN/SETTING: A modified rat laminectomy model was employed to assess epidural fibrosis using a quantitative biochemical collagen assessment approach along with correlative histology. This group served as the control for comparison with groups in which antifibrotic measures were employed. We compared antifibrotic efficacy of a bioabsorbable roofing barrier sheet placed over the laminectomy defect with topical high-molecular-weight hyaluronan (HMW HA) gel, each applied postoperatively to prevent proliferative epidural scarring. Routine biomechanical tensile strength testing was employed to assess wound-healing strength. METHODS: A bilateral laminectomy (L5 and L6) with associated unilateral disc injury (L5-L6) was performed in 98 male Harlan Sprague-Dawley rats. The laminectomy models described incorporated a unilateral disc injury at L5-L6 because herniated disc material has been shown to contribute proinflammatory cytokines in the postoperative wound. Five groups were employed for the study: 1) normal controls without surgery; 2) a laminectomy-disc injury group without treatment; 3) a laminectomy-disc injury group treated with topical HMW HA gel; 4) a laminectomy-disc injury group treated with 0.2-mm thick bioabsorbable roofing barrier sheet in which a protected space was maintained between overlying paraspinous muscles and the dura and 5) a 0.02-mm thin barrier sheet treatment group in which the sheet was placed directly on the dura. The animals were sacrificed at 3- and 8-week postoperative intervals for analysis. The dissected specimens were studied biochemically for hydroxyproline content to estimate total collagen within the canal and on the dura between L4 and L7. Additional specimens were prepared histologically and stained with Masson-Goldner Trichrome stain to confirm presence of proliferative collagen and to describe the presence or absence of wound-healing scar adherence to the dura. The surgical incisions were studied biomechanically by uniaxial tensile testing to determine ultimate force, strain and prefailure stiffness. Statistics were performed using analysis of variance. RESULTS: Gross appearance and histology studies showed that the untreated laminectomy group demonstrated postoperative scar formation that is adherent between the wound and the dorsum of the dura mater in both 3- and 8-week groups. Proliferative scar was substantially increased grossly between the 3- and 8-week intervals. By gross observation there was adherence of the L5 spinal nerve to the underlying disc and adjacent pedicle on the disc injury side. Gross observation of treatment groups, in contrast, disclosed that both the 0.2-mm thick roofing barrier sheet and topical HMW HA gel each prevented scar attachment to the dural sleeve at both the 3- and 8-week postoperative intervals. Furthermore, both the HMW HA gel and 0.2-mm thick roofing barrier sheet treatment groups had significant reduction of total collagen content in the laminectomy specimens measured biochemically at the two time periods compared with the untreated controls. Histologically, the HMW HA gel and the 0.2-mm thick barrier sheet findings were consistent with the gross observations concerning lack of adherence between scar of the overlying wound and the dura. Notably, both the 0.2- and the 0.02-mm barrier sheets became enveloped by a fibrotic envelope consistent with a foreign body reaction. In the group in which the 0.02-mm thin sheet was placed within the canal on top of the dura, there was an increase of fibrosis around the sheet within the canal leading to a space-occupying mass within the canal. Although the 0.2-mm thick roofing barrier placed external to the canal became enveloped by scar, it appeared to attract proliferative scar away from the epidural space, leaving the dura relatively free of scarring or adherence to overlying tissues. The mechanical properties of the incisional wound increased significantly between 3 and 8 weeks. The ultimate strength, stress, strain and stiffness of the several groups were similar at each time point. CONCLUSION: These results provide two preclinical rat laminectomy models of potential usefulness for the future study of the relevance of epidural fibrosis to behaviorally defined pain states, and for the study of the potential of an altered neurochemical signature in postlaminectomy pain conditions. Such preclinical models have become standard in studies of pain behavior and its neurochemistry in preclinical sciatic nerve and spinal nerve injury models, and should be of utility in the studies of postlaminectomy fibrosis. There was progressive scar proliferation and maturation in the untreated postlaminectomy group in the postoperative interval between 3 and 8 weeks. HMW HA gel applied topically and a 0.2-mm thick bioabsorbable Macropore sheet used as a roofing barrier each significantly reduced postlaminectomy proliferative scar without affecting the integrity of incisional wound healing. However, if the 0.02-mm thin barrier sheet used in this study is placed within the canal in contact with the dura and adjacent to the pedicles, the process of reabsorption results in a fibrotic mass within the canal. The preferred barrier sheet placement for this model is clearly in a roofing position bridging over the open epidural space. It must be placed in a manner to block off the paraspinous muscle healing response and still leave a gap between the sheet and the dura.     

Family physicians' perceptions of academic detailing: a quantitative and qualitative study

Background  

The efficacy of academic detailing in changing physicians' knowledge and practice has been the subject of many primary research publications and systematic reviews. However, there is little written about the features of academic detailing that physicians find valuable or that affect their use of it. The goal of our project was to explore family physicians' (FPs) perceptions of academic detailing and the factors that affect their use of it.