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.     

Time course of effects of brief inhalations of nitrous oxide in normal volunteers

Nitrous oxide is commonly used (abused) recreationally by inhaling it in a bolus form (i.e. single or several breaths). The time course of the psychoactive effects of nitrous oxide, via this mode of inhalation, has not been adequately characterized and thus formed the basis for this study. Twelve healthy volunteers participated in four sessions, using a randomized, cross-over, placebo-controlled design. In each session one of the following four measures were assessed: self-reported strength of drug effects, mood, memory and psyckomotor performance. Within sessions, subjects were exposed to four different concentrations of nitrous oxide in a randomized fashion: 0% (oxygen-placebo), 40%, 60% and 80%. At each concentration, or “trial”, subjects took four deep breaths of the gas. Peak drug effects, as reported by our subjects, occurred within 30 seconds after the last inhalation of nitrous oxide, persisted for about a minute, and then gradually subsided to near-baseline levels by 5 minutes post-inhalation. Certain aspects of mood were briefly affected by nitrous oxide, generally in a dose-related fashion with increases in visual analog scale ratings of “anxious”, “stimulated”, “coasting (spaced out)”, “lightheaded”, “confused”, and “high”. Free recall of words that had been presented between 30 and 60 seconds post-inhalation was significantly reduced after 80% nitrous oxide, relative to oxygen-placebo. There was a trend towards psychomotor impairment (Concentration x time: p – 0.08), as measured by the Digit Symbol Substitution Test, with peak decrements in performance (about a minute after inhalation) being greater after 80% nitrous oxide than after 0% nitrous oxide. Our results suggest that there arc acute, albeit brief, adverse effects of inhaling bolus concentrations of nitrous oxide.     

Alcohol, drug, and mental health problems among Jewish and Christian men at a university

Data from a questionnaire sent to 704 male university students and nonacademic staff were reanalyzed to compare self-reports of drug and alcohol intake patterns and problems as well as family histories of psychiatric disorders for Jewish (N = 110, Group 1) and Christian men (N = 594, Group 2). Although the two groups did not differ significantly on the quantity and frequency of alcohol intake, men in Group 2 were more likely to report at least one episode of heavy drinking and alcohol-related problems, and their responses indicated a higher rate of a family history of alcoholism. There were no differences across the groups on the proportion of lifetime drug use and related difficulties, or on the family histories of other psychiatric disorders. The results are consistent with previous studies demonstrating a lower prevalence of heavy drinking and related problems among Jews.     

Initial Blood Pressure Response to Captopril in Patients with Acute Myocardial Infarction, Related Factors and Mechanism

在82例急性心肌梗塞（AMI）的病人中探测使用卡托普利的初始血压反应的因素及机制。结果显示AMI病人对卡托普利的初始血压反应与心肌梗塞的部位、基础血压水平、心功能状态、RAS的活性及使用卡托普利的时间有关，RAS对卡托普利的反应可能是初始血压反应的主要机制。     

Arterial blood gases before, during, and after nitrous oxide:oxygen administration

The use of nitrous oxide as an anesthetic or analgesic agent frequently raises concerns about the possibility of post-inhalational diffusion hypoxemia. We undertook a study in 20 healthy volunteers to determine whether hypoxemia occurs after the self-administration by face mask of a 50:50 mixture of nitrous oxide and oxygen for 15 minutes, followed by breathing room air. Blood gases were measured through an in-dwelling arterial cannula before, during, and after inhalation of the mixture, at time O, five, ten, and 15 minutes, and then 30 seconds, 45 seconds, 2 1/2 minutes, five, and ten minutes following room air breathing. Ten of the 20 subjects breathed a control gas, a mixture of 50% nitrogen: 50% oxygen. No subject demonstrated arterial hypoxemia at any time before, during, or after self-administration of the gas mixture. In the ten subjects who self-administered the control gas there were no significant differences in the PaO2 values while they breathed either gas at any corresponding sampling time. We conclude that diffusion hypoxia is not seen in normal subjects following self-administration of a mixture of 50:50 nitrous oxide and oxygen.     

Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by the glutamate release-inhibiting drug lamotrigine

The present work was aimed at verifying the following hypotheses: (a) lamotrigine, a drug used to treat mood disorders, affects regulation of stress hormone release in humans, and (b) non-verbal behavior during mental stress situations (public speech) is related to hormonal responses. To achieve these aims, we performed a controlled, double-blind study investigating hormonal responses and non-verbal behavior during public speech in healthy subjects with placebo or lamotrigine (300 mg per os) pretreatment. The stress procedure was performed in 19 young healthy males 5 h following drug or placebo administration. Data were obtained from cardiovascular monitoring, blood and saliva samples, as well as the video-recorded speech. Pre-stress hormone levels were not affected by lamotrigine treatment. Lamotrigine significantly inhibited diastolic blood pressure, growth hormone and cortisol increases during psychosocial stress. In contrast, it potentiated plasma renin activity and aldosterone responses. Non-verbal behavior analysis revealed a correlation between catecholamines and submissive or flight behavior in controls, while between catecholamines and displacement behavior following lamotrigine administration. In conclusion, effects of lamotrigine on hormone release might be of value for its mood-stabilizing action used in the treatment of bipolar disorder. The data are in support of a stimulatory role of glutamate in the control of cortisol and growth hormone release during psychosocial stress in humans; however, further studies using more selective drugs are needed to prove this suggestion. The effects on plasma renin activity and aldosterone release observed seem to be related to other actions of lamotrigine.     

The efficacy of premixed nitrous oxide and oxygen for fiberoptic bronchoscopy in pediatric patients: a randomized, double-blind, controlled study

STUDY OBJECTIVE:s: The aim of the study was to evaluate the efficacy and safety of premixed 50% nitrous oxide and oxygen on the quality of sedation and pain control during fiberoptic bronchoscopy (FB) in children. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric pulmonary department in a pediatric tertiary university hospital. PATIENTS: One hundred five children aged 1 month to 18 years. INTERVENTIONS: Patients inhaled after sedation and local anesthesia either premixed 50% nitrous oxide and oxygen (nitrous oxide group) or premixed 50% nitrogen and oxygen (control group) during FB. Measurement and results: The rate of failure was significantly greater in the control group (62%) than in the nitrous oxide group (21%, p = 0.00003). The efficacy of premixed 50% nitrous oxide and oxygen was also demonstrated with higher satisfaction scores (p = 0.000001), lower Children's Hospital of Eastern Ontario Pain Scores (p = 0.002), better visual analog scale ratings (p = 0.03), and improved behavior scores. Side effects were minor and similar in both groups. CONCLUSIONS: This study demonstrates the improved efficacy of sedation, pain control, and safety of premixed 50% nitrous oxide and oxygen for FB in children.     

HIV, injecting drug use and harm reduction: a public health response

Injecting drug use is driving HIV epidemics in many countries around the world. There is evidence that such epidemics can be averted, halted and reversed if comprehensive HIV programmes targeting drug users are put into place. The term 'harm reduction' is used widely to describe the goals, policies and interventions of such programmes. However, despite its rapidly expanding use, the term has no universally accepted definition. This paper aims to describe the evolution and branding of the term 'harm reduction' and the adoption of the concept across a wide range of countries. It highlights a range of issues that remain controversial in the harm reduction discourse related to HIV and injecting drug use, including: the definition of 'harm reduction' and related terms; the scope of harm reduction; the promotion of a public health versus drug control dichotomy; the feasibility and appropriateness of harm reduction in low- and middle-income countries; and the strength of evidence on harm reduction interventions. The paper argues that harm reduction should be a core element of a public health response to HIV/AIDS where injecting drug use exists. The effectiveness of policies and programmes targeting drug users should be measured against public health outcomes. This requires the alignment of drug control measures with public health goals. A 'model package' for harm reduction is proposed, which provides guidance to countries on the selection of evidence-based policies and interventions, including: interventions for reducing HIV transmission; treatment of HIV/AIDS and associated comorbidities; appropriate models of service delivery; creation of supportive policy, legal and social environments; and strengthening of strategic information systems to better guide responses.     

The AmpliChip CYP450 test: principles, challenges, and future clinical utility in digestive disease.

Understanding genetically encoded inherited differences in drug metabolism and targets (ie, receptors, transporters) offers the promise of minimizing adverse drug reactions and improving therapies. Among the enzymes involved in drug metabolism, the cytochromes P450 (CYP450) hold a central position. In fact, CYP450 are involved in the biotransformation of most drugs used in clinical practice. Recent advances in the development of DNA-based diagnostics, coupled with a better understanding of genetic polymorphisms in influencing pharmacologic responses, have provided the foundation for novel in vitro tests that may predict side effects and/or therapeutic responses. The AmpliChip CYP450 test was developed as a clinical test to evaluate an individual's metabolic capacity for certain drugs by identifying polymorphisms of 2 CYP450 enzymes (ie, CYP2D6 and CYP2D19). Even though the AmpliChip CYP450 has been approved by the US Food and Drug Administration, its practical clinical utility has not yet been determined, and there is a paucity of data related to gastrointestinal and liver diseases. An understanding of the principles and opportunities provided by this new category of diagnostic test is key before planning the necessary studies to evaluate the usefulness of AmpliChip CYP450 in gastroenterologic clinical practice.     

Factors associated with abstinence,lapse or relapse to heroin use after residential treatment: protective effect of coping responses

Aims   This study investigates factors associated with abstinence, lapse or relapse to heroin use after residential treatment and, specifically, the extent to which changes in cognitive, avoidance and distraction coping responses were related to heroin use and other drug use outcomes.
Design, setting, participants  The sample comprised 242 clients from 23 residential programmes in the NTORS project, who used heroin before treatment and who were followed-up after treatment during the first 12 months of the study.
Measurements   Data on client characteristics and problems, coping responses, drug use and other outcomes, were collected by structured face-to-face interviews.
Findings   Many clients (60%) used heroin after treatment, with the first occasion of heroin use usually occurring very soon after leaving treatment: 40% remained abstinent from heroin. Analyses were conducted for three groups based upon heroin outcome status (abstinent, lapsed, relapsed). Clients who avoided a full relapse to heroin use (abstinent and lapse groups) consistently made more use of cognitive, avoidance and distraction coping strategies at follow-up than at intake. Treatment completion was related to better outcome. The lapse and relapse groups reported higher rates of use of illicit drugs other than heroin after treatment than the abstinent group.
Conclusions  Despite generally satisfactory drug use outcomes, the lapses and relapses to heroin use give rise to concern. Treatment services should develop further and strengthen relapse prevention and relapse coping skills among drug misusers.     

Piroxicam treatment protects mice from lethal pulmonary challenge with Pseudomonas aeruginosa

The effect of treatment with the nonsteroidal anti-inflammatory agent piroxicam on leukocyte migration to the lungs was investigated after aerosol administration of sublethal doses of Pseudomonas aeruginosa to mice. Piroxicam decreased, in a dose-related fashion, the polymorphonuclear leukocyte recruitment to, and the degree of perivascular and peribronchial infiltration in, the lungs. Piroxicam treatment also protected the animals in a dose-dependent manner from challenge with lethal doses of P. aeruginosa. The effect of piroxicam was not related to direct action of the drug on the microorganisms. Piroxicam treatment maintained the animal's pulmonary defenses against infection while diminishing inflammatory responses against P. aeruginosa, an occurrence decreasing the potential for tissue damage due to phagocytes migrating from circulation.     

单核苷酸多态性与哮喘个体化治疗

哮喘的异质性既包括遗传、环境因素的多样性,也包括患者对治疗反应的差异性.哮喘患者的药物治疗反应差异可能与基因单核苷酸多态性(single nucleotide polymorphisms,SNP)有关.药物-基因组学旨在研究药物作用及代谢通路上的关键分子,并探索相关基因SNP与药物疗效的关系.哮喘药物-基因组学研究有助...     

Peripheral polyneuropathy and acute psychosis from chronic nitrous oxide poisoning: A case report with literature review

Rationale:Nitrous oxide (NO) is a commonly used drug in medical practice, restoration, and the automobile industry. Recreational abuse is an emerging public health problem owing to its accessibility and drug properties.Patient concerns:A 25-year-old male was hospitalized with acute psychosis and lower-extremity sensorimotor proprioceptive ataxia due to nitrous oxide abuse.Diagnosis:Laboratory studies confirmed a vitamin B12 deficiency. Magnetic resonance imaging of the spinal cord showed normal findings. Electrophysiological testing confirmed length-dependent sensorimotor polyneuropathy, with a predominant motor component and axonal degeneration.Intervention and outcomes:Abstinence from toxic substances was suggested, and vitamin B12 substitution was introduced. The patient was lost to follow up.Lessons:Nitrous oxide toxicity is multisystemic and is thought to result from vitamin B12 inactivation. Recent case reports postulated direct paranodal lesions resulting from nitrous oxide consumption. Neurological, neuropsychiatric, and hematological toxicities are among those explored in this case report. Correction of the functional vitamin B12 status and nitrous oxide abstinence are essential in the treatment process.     

Safety and efficacy of statins in Asians

Asian patients frequently have heightened responses to therapeutic drugs. As a consequence, the recommended drug doses are often lower in Asian countries than in Western countries. This practice extends to the use of cardiovascular drugs, including statins for the treatment of dyslipidemia. Pharmacokinetic investigations have noted higher plasma levels of statins in Asians compared with Caucasians, although postmarketing data for all statins have not identified any particular safety issues, even when statins are given at equivalent doses. The potential mechanisms of heightened response to statins in Asians are related to genetically based differences in the metabolism of statins at the level of hepatic enzymes and drug transporters. Studies indicate that lower statin doses achieve lipid improvements in Asian patients comparable with those observed with higher doses in Caucasians. In conclusion, prescribing lower starting doses of statins in Asians appears warranted while research on this subject continues.     

Comparison of the effects of amrinone and sodium nitroprusside on haemodynamics, contractility, and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy

The effects of intravenous amrinone and sodium nitroprusside on haemodynamic indices, left ventricular contractility, and myocardial metabolism were compared in patients with cardiac failure. All patients received one dose of each drug and some received serial doses. Eight patients had dilated cardiomyopathy and six coronary artery disease, but the responses to the two drugs were independent of the aetiology of cardiac failure. Both drugs lowered left ventricular end diastolic pressure and aortocoronary sinus oxygen difference and increased cardiac index and left ventricular efficiency; these effects were dose related. Although the effects of the drugs on peripheral blood substrate concentrations were different, those on myocardial substrate metabolism were identical. Pressure derived indices of contractility in each group of patients were unaltered by either drug. After amrinone administration increases in cardiac index were related to plasma amrinone concentration, but alterations in contractility were not. In four individual patients increases in contractility were associated with alterations in plasma metabolite concentrations, which suggested that catecholamine release had occurred. For the groups of patients as a whole, however, amrinone had effects which did not differ significantly from those of the pure vasodilator, nitroprusside. There was no evidence that amrinone had a direct positive inotropic effect since no dose related changes in indices of contractile function could be established.     

Comparison of the effects of amrinone and sodium nitroprusside on haemodynamics, contractility, and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy.

The effects of intravenous amrinone and sodium nitroprusside on haemodynamic indices, left ventricular contractility, and myocardial metabolism were compared in patients with cardiac failure. All patients received one dose of each drug and some received serial doses. Eight patients had dilated cardiomyopathy and six coronary artery disease, but the responses to the two drugs were independent of the aetiology of cardiac failure. Both drugs lowered left ventricular end diastolic pressure and aortocoronary sinus oxygen difference and increased cardiac index and left ventricular efficiency; these effects were dose related. Although the effects of the drugs on peripheral blood substrate concentrations were different, those on myocardial substrate metabolism were identical. Pressure derived indices of contractility in each group of patients were unaltered by either drug. After amrinone administration increases in cardiac index were related to plasma amrinone concentration, but alterations in contractility were not. In four individual patients increases in contractility were associated with alterations in plasma metabolite concentrations, which suggested that catecholamine release had occurred. For the groups of patients as a whole, however, amrinone had effects which did not differ significantly from those of the pure vasodilator, nitroprusside. There was no evidence that amrinone had a direct positive inotropic effect since no dose related changes in indices of contractile function could be established.     

HIV infection and intravenous drug use: critical issues in transmission dynamics, infection outcomes, and prevention

As the second largest group of persons to have been infected with human immunodeficiency virus (HIV), and the most likely to transmit HIV to heterosexual partners in the United States and Europe, iv drug users will play an increasingly important role in the future of the AIDS epidemic. This paper reviews five emerging critical issues regarding HIV infection among iv drug users. In epidemiology, rates of drug injection and anonymous sharing of injection equipment appear related to rapid spread of HIV among iv drug users, while heterosexual transmission from iv drug users appears to have been occurring at a relatively slow but constant rate. Data exist that support a gender-related cofactor and a continuing drug injection cofactor, but mechanisms for these potential cofactors have not been determined. Besides frank AIDS, HIV infection also appears to lead to epidemic-level increases in a variety of fatal infections among iv drug users. Several studies of prevention show active risk reduction among iv drug users, but new methods are urgently needed to increase amount of risk reduction.     

Types of Arrests Recorded for Methadone Maintenance Patients Before, During, and After Treatment

The police records of 65 male heroin addicts were compared before and after admission to a methadone maintenance program for occurrences of (1) violence, (2) property, and (3) drug related arrests. Occurrences of arrests for all three categories of crime decreased while the men were in treatment, and the police records of 19 men who prematurely left treatment indicated that their incidences of arrests for violence, property, and drug related crimes did not increase after leaving the program. The conclusions were drawn (1) that male addicts' incidences of arrests are reduced after admission to a methadone maintenance program and (2) that dropouts from methadone maintenance have incidences of arrests comparable to those incurred while in treatment.     

Assessing consistency of responses to questions on cocaine use

This study examines consistency of self-reported responses to items within the questionnaire of a multi-site, prospective study of drug abuse treatment in the United States (DATOS). The analyses use data from 2842 interviewer-administered intake interviews. Questions that were logically related are paired and responses compared. The questions cover three topics: (1) age at which different types of cocaine was used, (2) reports on most recent use and (3) frequency of cocaine use during period of “heaviest” use. Responses are coded as consistent, inconsistent, or as survey administration error. The latter is related to interviewer errors such as erroneous skip pattern, out-of-range responses, “don't know” responses, missing data, or illegible responses. Contrary to expectations inconsistent responses were relatively rare in this study, with fewer than 5% (0.5–4.6%) of respondents reporting inconsistent answers for pairs of logically related questions. A careful review of responses also found few survey administration errors (0.2–1.3%).     

Prefixed equimolar nitrous oxide and oxygen mixture reduces discomfort during flexible bronchoscopy in adult patients: a randomized, controlled, double-blind trial

STUDY OBJECTIVES: Flexible bronchoscopy (FB) is an invasive procedure associated with patient discomfort and frequent nose pain. A simple sedation procedure that does not require the intervention of an anesthetist is of interest. The aim of this prospective, randomized, double-blind study was to assess efficiency of nitrous oxide inhalation on the reduction of FB-induced discomfort in adult patients. DESIGN AND SETTINGS: Two hundred six patients were randomized to receive either a prefixed equimolar nitrous oxide/oxygen mixture (N2O) or a prefixed equimolar nitrogen and oxygen mixture (control). The primary outcome was stress as assessed by pulse rate and systemic BP during the procedure. Secondary outcomes were self-assessed pain using a visual analog scale (VAS) and patient satisfaction based on a questionnaire. Adverse events were recorded. RESULTS: A significant increase in BP was observed only in the control group (p = 0.003), while pulse rate values did not differ between the two groups. As assessed by the VAS, pain was lower in the N2O group as compared to placebo (p = 0.02). Nose pain and cough were also significantly reduced by N2O. Adverse events, mostly anxiety, were reported in 10 patients. CONCLUSION: These results indicate that equimolar N2O inhalation is efficient in reducing patient discomfort and may be an alternative to general anesthesia.