Single Aortotomy for Multiple Aortocoronary Saphenous Vein Bypass Grafts

A new technique for the proximal anastomoses of saphenous vein grafts in coronary artery bypass operations is described. This technique has several advantages over existing methods and has been shown to be safe and satisfactory in 389 consecutive patients operated on between May, 1978, and May, 1981.     

Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27

Recent experimental observations have suggested that statins may exert modulatory effects on a number of pathobiological processes beyond their cholesterol-lowering properties. Some of the pleiotropic effects of statins seem to be mediated by their ability to block the synthesis of isoprenoid intermediates, which serve as important lipid attachments required for the proper function and activation of the small GTP-binding proteins. The current study explored the modulatory effects of simvastatin (SMV) on the angiotensin II (Ang II)-induced Rac1-mediated, upregulation of cyclin-dependent kinase inhibitor p27. Ang II (100 nM) stimulation of rat mesangial cells induced a significant increase in p27 protein expression. Co-treatment of cells with SMV (1 microM) inhibited Ang II-induced upregulation of p27 protein. Addition of mevalonate (200 microM) or geranylgeranyl pyrophosphate (5 microM) reversed the inhibitory effect of SMV on p27 protein expression, suggesting that the effect of SMV is geranylgeranyl dependent. This study also provides evidence for a sequential link between Ang II stimulation and downstream activation of Rac1, intracellular H2O2 production, and Akt kinase leading to upregulation of p27 protein in mesangial cells. It was also shown that SMV, by inhibiting Rac1 activity, reversed Ang II-induced increase in intracellular H2O2 production, Akt activation, and p27 protein expression. The data presented in this study not only elucidate Ang II-mediated signaling cascade in mesangial cells but also demonstrate for the first time the modulatory effects of SMV on Ang II-induced signaling pathway at the cell cycle level.     

Magnitude and impact of treatment delays on weeknights and weekends in patients undergoing primary angioplasty for acute myocardial infarction (the cadillac trial)

In 2,082 patients in the CADILLAC trial, the outcomes of patients presenting during peak hours were compared with those presenting during peak hours (Monday to Friday 8a.m. to 8 p.m., n = 1,047, 51%) were compared with those of patients presenting during off-peak hours (weeknights from 8 p.m. to 8 a.m. and weekends, n = 989, 49%). Although treatment times to percutaneous coronary intervention (PCI) were delayed approximately 21 minutes, in patients with acute myocardial infarctions occurring on weeknights and weekends, this modest delay did not adversely affect procedural success, myocardial recovery, or survival after PCI.     

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study

In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two (18)F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order--one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.     

Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder

This study was designed to compare the effects of fluoxetine and imipramine on fasting blood glucose (FBG) in patients with major depressive disorder. Sixty nondiabetic patients with major depressive disorder (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) entered this randomized, double-blind study. Patients did not receive any medication affecting serum FBG levels for at least 2 weeks before the initiation of the study. Patients were assigned to receive 20 to 40 mg/d of fluoxetine or 75 to 200 mg/d of imipramine for 8 weeks. Pregnant women and patients with diabetes mellitus and a history of any major heart disease were excluded from this study. Additionally, none of the patients should have received electroconvulsive therapy within 6 months before the initiation of the antidepressants. FBG levels were measured at the initiation, as well as 4 and 8 weeks after starting antidepressants. Nineteen patients in the fluoxetine and 24 patients in the imipramine groups completed the study. In the fluoxetine group, FBG level was decreased from 88.5 mg/dL (baseline) to 85.0 mg/dL at week 4 (P = 0.73), and to 79.8 mg/dL at week 8 (P < 0.001). On the other hand, in the imipramine group, FBG level was increased from 86.96 mg/dL (baseline) to 89.71 mg/dL at week 4 (P = 0.079), and to 96.90 mg/dL at week 8 (P < 0.001). This 8-week study showed that FBG levels may decrease in depressive patients receiving fluoxetine and may increase in those patients treated with imipramine. Therefore, it is suggested to measure and monitor FBG before initiation and during treatment with fluoxetine and imipramine.     

The influence of drug type on the release profiles from Surelease-coated pellets

The release of metoclopramide hydrochloride (a water-soluble cationic drug) and diclofenac sodium (a sparingly soluble anionic drug) from pellets coated with ethylcellulose from an aqueous ethylcellulose dispersion (Surelease) at different coating loads was investigated. The release rates of each drug decreased as the coating load of Surelease increased. However, despite its lower water solubility, diclofenac sodium was released slightly faster than metoclopramide hydrochloride at equivalent coating loads. Changes in the release rates after curing were more pronounced for metoclopramide hydrochloride and the release rates of diclofenac sodium were lower than those of metoclopramide hydrochloride after curing. Differences between the release behaviour of the two drugs were probably due to an interaction between the cationic metoclopramide and the anionic ammonium oleate present in the Surelease. The slower release of metoclopramide hydrochloride may be due to an in situ formation of a poorly soluble complex of the drug and the ammonium oleate. This complex, because of its large molecular size, may diffuse more slowly through the film, causing a reduction in the release rate of metoclopramide hydrochloride. This interaction may also account for the differences in release characteristics of the drugs after curing. During curing the surfactant, due to its unstable nature in heat, may be converted to its constituent components. The interaction of drug with the surfactant was reduced as the residue of the ammonium oleate decreased during curing. However, a relatively low volume flow rate of air, and therefore, slower removal of ammonia in the modified side-vented Manesty Accela-cota 10 may also have affected the coating process of the pellets.     

Bilateral chylothorax following neck dissection: a new method of treatment

Chylothorax is a serious condition with a high rate of morbidity that may lead to death. Although it is encountered more frequently with certain thoracic procedures, it is considered to be a rare complication of neck dissection. Different forms of management have been postulated; however, no consensus of treatment has been achieved. A case of severe bilateral chylothorax that developed after bilateral neck dissection in a patient with laryngeal carcinoma is presented. Somatostatin injection was successful after total parenteral nutrition failed to control the chylothorax. On the basis of this case and the review of the literature discussed here, we advocate the use of somatostatin with other conservative measures in the management of chylothorax.     

Reinforcing, subjective, and psychomotor effects of sevoflurane and nitrous oxide in moderate-drinking healthy volunteers

Aims. To characterize the reinforcing, subjective and psychomotor effects of sevoflurane, a volatile anesthetic, across a range of subanesthetic concentrations in non-drug-abusing humans. In addition, a concentration of nitrous oxide was included in the design in order to compare and contrast behavioral effects of a gaseous to a volatile anesthesic. Design. Repeated measures, double-blind, placebo control experiment. Setting. Human psychopharmacology laboratory. Participants. Fourteen moderate-drinking healthy volunteers. Intervention. In each of four sessions, subjects first sampled placebo-oxygen and an active drug (end-tidal concentrations of 0.2, 0.4, 0.6% sevoflurane and 30% nitrous oxide in oxygen) and then chose between the two. Measurements. Mood and psychomotor performance during the sampling trials, and choice of drug or placebo-oxygen during choice trial. Findings. Nitrous oxide was chosen by 71% of the subjects, and 0.2, 0.4 and 0.6% sevoflurane were chosen by 50%, 57% and 50% of the subjects, respectively. Neither drug was chosen at levels that exceeded that of chance. Sevoflurane and nitrous oxide both impaired psychomotor performance and produced changes in mood. There were several differences in subjective effects between sevoflurane and nitrous oxide at concentrations which were considered to be equivalent in anesthetic effect. Finally, although sevoflurane did not function as a reinforcer in the majority of individuals tested, there was evidence that sevoflurane functioned as a reinforcer in some volunteers: subjects who chose to inhale sevoflurane over placebo-oxygen tended to report a positive spectrum of subjective effects during the sevoflurane sampling trial, relative to those subjects who chose placebo-oxygen over sevoflurane. Conclusions. Although sevoflurane did not function as a reinforcer in the majority of subjects tested, the correspondence between positive subjective effects of sevoflurane and subsequent sevoflurane choice suggests that the volatile anesthetic drug can function as a reinforcer in some moderate drinkers.