Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

Single-Agent versus Combination Antibiotic Therapy in the Management of Intraabdominal Infections

For the treatment of intraabdominal infection, single-agent antimicrobial regimens such as β-lactams with good antianaerobic activity are frequent alternatives to combination regimens such as aminoglycosides or aztreonam plus an antianaerobic agent such as clindamycin or metronidazole. The major issues in selecting a regimen are relative efficacy, potential for adverse drug effects, and cost. Single agents are clearly equivalent to combinations in preventing infectious complications after penetrating abdominal trauma and in treating established intraabdominal infections of mild to moderate severity or in relatively low-risk patients. A few trials demonstrated their equivalency in patients at high risk of mortality, although experience is limited. Single-agent regimens may reduce the risks of adverse drug effects compared with combination regimens, but they are not always less expensive.     

Ampicillin-Sulbactam versus Cefoxitin for Prophylaxis in High-Risk Patients Undergoing Abdominal Surgery

This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery. Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures. Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later. Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second. Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group. The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p>0.05); one wound infection occurred in each group. Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p>0.05). Cost-minimization analysis revealed that ampicillin-sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery.     

Phase II evaluation of merbarone in renal cell carcinoma

Summary The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m² IV continuous infusion days 1–5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1–15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.     

Induction of collagenase synthesis in chondrocytes by a factor synthesized by inflamed synovial tissue

Rabbit inflamed synovial tissue grown in culture synthesizes a factor that induces collagenase synthesis in chondrocytes and in cartilage. Synthesis of this factor by the synovial tissue is inhibited by cycloheximide but not by indomethacin. The factor has an apparent molecular weight of 30,000, is stable to heat and to trypsin treatment but is inactivated by acid. Induction of collagenase synthesis in chondrocytes occurs after a lag period of 6 hours.     

育龄妇女月经周期中心血管功能的变化

本研究采用先进的三维超声成像技术及多普勒技术对正常育龄妇女月经周期中心血管功能进行研究。结果：月经周期中ＨＲ、ＢＰ无变化；血清Ｅ２是周期性变化，排卵前达高峰。ＳＶ、ＣＯ、ＥＦ在排卵前期升高达峰值，显著高于月经期和黄体期；ＳＶＲ排卵前期最低，而Ｖｅｄ、Ｖｅｓ无变化。Ｖｍａｘ、Ａ、Ｅ在内源性Ｅ２高峰时明显加快，而Ｅ／Ａ比值无明显变化。结果提示：月经周期中随内源性Ｅ２的周期性变化，心脏功能也发生周期性变化。Ｅ２高峰时，心输出量、心搏量和射血分数达最高。外周阻力最低，心脏内血流速度加快。     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

The Influence of Routine Completion Arteriography on Outcome following Carotid Endarterectomy

n = 69) normal; Group B (n= 29), abnormal, severe defects; Group C (n= 56), abnormal, mild–moderate defect. RCA detected 32 defects in Group B: 10 internal carotid (ICA), seven endpoint flaps, two kinks, one dissection; 16 external carotid (ECA), 10 severe endpoint defects and six total occlusion; six common carotid (CCA), five irregular proximal shelfs, one web. Thirty of 32 defects were successfully repaired as confirmed by normal repeat RCA studies; one ECA defect was not repaired and the ICA dissection was irreparable. In Group C, 67 mild–moderate defects were identified, but not corrected. These included <30% stenosis in the ICA (12), ECA (18), CCA (24), and vein patch corrugation or irregularity (13). For the entire series the postoperative ICA occlusion rate was 2% (3/154), stroke rate 2.6% (4/154), and a subsequent >50% restenosis rate of 7% (11/154). The yield from routine carotid completion arteriograms was significant, with 19% of studies identifying a severe defect that required repair. Although the difference in stroke rates and restenosis between the different groups did not reach statistical significance, patients with normal intraoperative arteriograms initially or after correction of a significant RCA defect had no early carotid occlusion (p= 0.05, Fisher's exact test) compared to patients with residual RCA defects. All early carotid occlusions occurred in patients with unrepaired defects. We conclude that RCA is an important method of quality control after CEA and exerts a subtle, but real, reduction in postoperative complications.     

Comparison of polychlorinated dibenzodioxin levels with hepatic mixed-function oxidase induction in great blue herons

As part of the Canadian Wildlife Service monitoring of great blue herons in British Columbia, eggs were collected from three colonies with low, intermediate, and high levels of PCDD and PCDF contamination: Nicomekl, Vancouver, and Crofton, respectively. One egg from each nest was used for chemical analysis by GC-MS; the others were hatched. Liver microsomes were prepared from the heron chicks and used for determination of cytochrome P-450-dependent activities. No erythromycin N-demethylase activity was found in any sample. Ethoxyresorufin O-dealkylase activity in the Nicomekl group was similar to that in pigeons, a control altricial species. The ethoxyresorufin activity in the herons from the Crofton colony was 2.6-fold higher than in the Nicomekl group. The Vancouver colony was intermediate. No difference among the three heron colonies was found in pentoxyresorufin O-dealkylase activity, although levels were 20-33 times that in the pigeon. Chemical analysis was carried out on paired heron eggs. Vancouver and Crofton eggs contained 13.5 and 21 times the levels of 2,3,7,8-TCDD compared to the Nicomekl group. The Crofton eggs contained higher levels of several other contaminants also. A highly significant correlation (p less than .001) was found between ethoxyresorufin O-dealkylase and 2,3,7,8-TCDD concentrations. The correlation coefficient did not change when ethoxyresorufin O-dealkylase was compared to total chemical contamination using several toxic equivalency factors. Multiple regression analysis resulted in only one predictor variable for ethoxyresorufin O-dealkylase: 2,3,7,8-TCDD.     

59例老年非何杰金氏淋巴瘤病理分析

本文报道老年非何杰金氏淋巴瘤(NHL)59例并与同期非老年患者138例相比。老年患者占同期NHL总数的29.9％。59例中有结内型43例,结外型16例;低度恶性与中度恶性各12例,高度恶性35例。与非老年组比较,老年组的就诊原因、病变部位、恶性程度、细胞类型和预后等方面无何差别,提示年龄对上述特征无明显影响。