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.     

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.     

Does the mode of inhalation affect the bronchodilator response in patients with severe COPD?

Spacing devices improve lung deposition of aerosols from metered dose inhalers (MDI) but it is sometimes difficult for dyspnoeic patients to perform maximal breaths with breath-holds needed to inhale the aerosols from them. Our aim was to determine whether the response to bronchodilators (BD) depended on the method of inhalation. We studied 20 patients with moderately severe chronic obstructive pulmonary disease (COPD) with a mean age of 68 years and a mean of forced expiratory volume in 1 sec (FEV1) of 41% predicted. In a randomized, cross-over fashion they inhaled terbutaline 1.5 mg (six puffs) followed by ipratropium 120 microg (six puffs) via MDI and nebuhaler with either two inspirations to total lung capacity and a 10-sec breath-hold per puff or with six tidal breaths per puff. Before and after BDs we measured FEV1, forced vital capacity (FVC), airways resistance using interrupter method (Rint) and 6-min walking distance (6MWD). Subsequently, we re-tested nine of these patients with the two methods of inhalation, before and after conventional doses (terbutaline 500 microg+ipratropium 40 microg), then after terbutaline 1 mg and ipratropium 80 microg and finally after nebulized terbutaline 5 mg and ipratropium 500 microg to sec whether there was a dose-dependent difference in effect between the two methods. Spirometry, slow vital capacity (SVC). inspiratory capacity and shuttle walking tests were monitored. In the original 20 patients there were highly significant improvements in all parameters after inhalers, with no significant difference between methods of inhalation. Median improvements after BDs were: FEV1 0.221 and 0.191, FVC 0.501 and 0.381 and 6MWD 40 m and 44 m, for maximal breaths and tidal breathing, respectively. For nine patients, tidal and maximal breaths produced similar effects on lung function and exercise tolerance at both doses of BDs. Nebulized BDs only improved shuttle distances slightly when compared with either method of inhalation from MDI and spacer but had no additional effect on lung function. In conclusion, in patients with moderately severe COPD, BDs given by metered dose inhaler via nebuhaler have similar effects whether given by six easy tidal breaths or the more difficult two maximal breaths with breath-hold. This holds true at small or larger doses of BD. Either method of inhaling six puffs of the BDs can be used as an effective alternative to nebulized aerosol.     

Personality, prior drug use, and introspective experience during nitrous oxide intoxication

This report compares data on some personality characteristics and prior drug experiences of 60 volunteer young men with their subjective psychological responses while inhaling 40% nitrous oxide-oxygen mixtures for 20 min in a naturalistic laboratory setting. A rather specific trait-openness to "internal," reverie-type experiences-was very significantly related to a wide variety of drug responses, while several more general traits-including introversion and neuroticism-and openness to nonreverie mental experiences were unrelated to drug response. Prior illicit drug use was related only to mood on nitrous oxide, and not to other effects. Implications of the findings in the field of drug abuse are discussed.     

吸入一氧化氮治疗肺动脉高压的作用机理与应用评价

目的对吸入一氧化氮（NO）治疗肺动脉高压的临床药理学与临床毒理学进行评价。方法30例成人和54例儿童肺动脉高压患者吸人NO治疗。吸入前、吸入后30min和停吸后2h、24h分别取血浆测定NO代谢产物（NO_2~-）的浓度以及环磷酸鸟苷（cGMP）、丙二醛（MDA）和内皮素（ET-1）的水平，取循环白细胞测定一氧化氮合成酶（NOS）的活性。结果吸入NO后血中一氧化氮的浓度明显增加（P＜0．01），信息传递物质cGMP水平显著升高（P＜0．05），而脂质过氧化代谢产物MDA没有增多（p＞0．05），ET-1水平保持不变（P＞0．05），NOS活性不受影响（P＞0．05）。结论外源性NO亦通过cGMP发挥作用。当吸入浓度维持在一定范围内时，NO作为药物治疗是基本安全、有效的，因此NO是一种极具潜力的选择性肺动脉扩张剂。     

The effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects

Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5 micron triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced responses to aerosolized bronchodilator therapy in asthma using respiratory maneuvers.

To determine if respiratory maneuvers may enhance the response to inhaled bronchodilator drugs, we evaluated the bronchodilator responses when isoproterenol was: inhaled as a bolus high (80 percent VC) compared to low (20 percent VC) lung volumes, and inhaled as a single 800 microgram dose compared to four 200 microgram doses given 20 min apart. Nine asthmatic subjects inhaled isoproterenol sequentially at high and low lung volumes on two separate days; 15 others inhaled single doses of 200, 400, 600, and 800 microgram isoproterenol on four separate days. FEV1, specific conductance (Gaw/VL), Vmax50%, and the slope of phase 3 of the single-breath nitrogen test (deltaN2/L) were measured 10 min after each dose. FEV1 and Gaw/VL increased and deltaN2/L decreased more following inhalation at high compared to low lung volume (P less than 0.05). Gaw/VL increased more in the group given 800 microgram in divided doses than the group given a single dose (P less than 0.05). These findings suggest that the bronchodilator response to isoproterenol may be enhanced by inhaling the drug in divided doses sequentially and by delivering the drug near maximal inspiration. An enhanced response after the latter maneuver may be due to more uniform distribution of the drug to airway receptor sites.     

Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection.

Inhalation of histamine diphosphate aerosol (1.6 per cent, 10 breaths) produced a 218 +/- 54.6 per cent (mean +/- SE) increase in airway resistance in 16 normal subjects with colds compared with a 30.5 +/- 5.5 per cent increase in 11 healthy control subjects (P less than 0.01). There was no significant difference in mean baseline airway resistance between the two groups. Inhalation of saline produced no significant change in airway resistance in either group. Isoproterenol hydrochloride (0.5 per cent, 1 breath) or atropine sulfate aerosol (0.2 per cent, 20 breaths) each reversed and prevented the increase in airway resistance by histamine, indicating that the bronchoconstriction was caused by smooth muscle contraction and that post-ganglionic, cholinergic pathways were involved in the mechanism. In 6 subjects with colds, citric acid aerosol (10 per cent, 5 breaths) caused bronchoconstriction that lasted up to 30 sec after inhalation, a significantly greater effect than that observed in control subjects or in the same subjects after recovery (P less than 0.05). Prior inhalation of atropine aerosol (0.2 per cent, 20 breaths) prevented the bronchoconstriction after citric acid aerosol in all 6 subjects. The threshold concentration of citric acid that produced cough in 7 subjects with colds was significantly lower than that in control subjects or in the 7 subjects after recovery (P less than 0.05), suggesting that the exaggerated cholinergic response was due to a decreased threshold for stimulation of the rapidly adapting sensory receptors in the airways. We have provided evidence that respiratory viral infections that produce airway epithelial damage temporarily cause these subjects to develop more bronchoconstriction after inhaling smaller doses of histamine than do healthy subjects. The fact that atropine prevents this response and that the threshold to cough is temporarily decreased is compatible with our hypothesis that airway epithelial damage by infection exposes and, thus, "sensitizes" the rapidly adapting airway receptors to inhaled irritants, causing increased bronchoconstriction via a vagal reflex. Damage to the airway epithelium may occur as a result of mechanical factors, inhaled chemicals, and pollutants, such as ozone, infections, or perhaps as a result of the action of materials released endogenously (e.g., from mast cells, white blood cells, or platelets). "Sensitization" of rapidly adapting sensory receptors in the airways may be an important factor in asthma and in other diseases of airways.     

A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair

STUDY OBJECTIVE: To compare the efficacy and complication profile of oral midazolam therapy and continuous-flow 50% nitrous oxide in alleviating anxiety during laceration repair in children 2 to 6 years old. METHODS: We conducted a prospective, randomized clinical trial using 4 study groups who required laceration repair: (1) children who received standard care alone, which included comforting and topical anesthesia augmented with injected lidocaine if needed; (2) children who received standard care and oral midazolam; (3) children who received standard care and nitrous oxide; and (4) children who received standard care, oral midazolam, and nitrous oxide. Videotapes were blindly scored using the Observational Scale of Behavioral Distress-Revised (OSBD-R) to assess distress during baseline, wound cleaning, lidocaine injecting, suturing, and recovery. Adverse effects were noted during suturing and by parent questionnaires completed 24 hours after suturing and at suture removal. OSBD-R data were analyzed using repeated-measures analysis of variance. Adverse effect data were analyzed using categorical models. RESULTS: Two hundred four subjects were enrolled (midazolam plus nitrous oxide 52, midazolam 51, nitrous oxide 51, standard care 50; mean patient age was 4.1 years; 66% were boys). Mean OSBD-R scores were lower for groups that received nitrous oxide during wound cleaning by 2.2 points (95% confidence interval [CI] 1.1 to 3.2), lidocaine injecting by 2.5 points (95% CI 1.4 to 3.5), and suturing by 2.9 (95% CI 1.8 to 3.9). Adverse effects occurred more frequently, and recovery times were longer for groups that received midazolam. CONCLUSION: For facial suturing in 2- to 6-year-old children, regimens including continuous-flow nitrous oxide were more effective in reducing distress, and had fewer adverse effects and shorter recovery times than midazolam.     

Inhibitory effect of gas phase cigarette smoke on breathing: role of hydroxyl radical

Inhaling cigarette smoke evokes immediate bradypnea in rats, resulting from stimulation of vagal bronchopulmonary C-fiber afferents by smoke constituent(s) other than nicotine. To determine the contribution of the gas phase of smoke to this irritant effect, the acute respiratory responses to both cigarette smoke and gas phase smoke were studied and compared in anesthetized Sprague-Dawley rats; smoke (6 ml, 50%) was generated by a machine from low-nicotine research cigarettes and the gas phase was obtained by passing the smoke through a glass-fiber Cambridge filter. Inhalation of gas phase smoke alone evoked a transient inhibitory effect on breathing, prolonging expiratory time (Te) to a peak of 159 +/- 6% of the base line; this response was very similar to that triggered by inhaling the unfiltered smoke (Te = 177 +/- 12%). The bradypnea started within 1-4 breaths after the onset of smoke inhalation, lasted for 3-5 breaths and was completely abolished by vagotomy. This inhibitory effect of gas phase smoke on breathing was also largely prevented after a pretreatment with either intravenous infusion or aerosol inhalation of a hydroxyl radical scavenger, dimethylthiourea. These results suggest that the gas phase is primarily responsible for eliciting the reflexogenic bradypneic response to cigarette smoke in anesthetized rats and that hydroxyl radicals released endogenously in the lungs may be involved.     

Acute effects of liposome aerosol inhalation on pulmonary function in healthy human volunteers

Administering liposome-encapsulated drugs by aerosol is a feasible way of targeting drugs to the lungs. Prior to clinical application of aerosolized liposomes as drug carriers, their relative safety must be established. We evaluated the effects of inhaling nondrug-containing liposomes (15 and 150 mg of lipid per milliliter) for 1 h on pulmonary function and on oximetry in ten healthy nonsmoking volunteers. Spirometry was performed prior to and at intervals after inhalation, and subjects were monitored with pulse oximetry. Liposome inhalation was well tolerated, and no oxygen desaturation, decrements in pulmonary function, or side effects were noted. We conclude that inhalation of small particle aerosols of SPC liposomes produces no acute deleterious effects on pulmonary function in healthy subjects.     

一氧化氮对缺氧性肺动脉高压大鼠血流动力学及肺组织结构的影响

为探讨吸入一氧化氮（NO）对慢性缺氧性肺动脉高压的疗效及毒副作用，本文对正常（NN）组和慢性缺氧（HN）组大鼠吸入10～80ppmNO测定其血流动力学、血气和高铁血红蛋白（MetHb）变化，并对正常对照（NC）组、慢性缺氧对照（HC）组、NN组和HN组肺组织进行常规组织学及透射电镜观察。结果显示：HN组吸入NO后，肺动脉平均压（mPAP）和肺血管阻力（PVR）明显降低，且PVR降低程度与NO浓度呈效量依赖性，但吸人80PPmN时mPAP未较吸入40ppmNO时进一步降低；吸入NO对NN组和HN组体循环血流动力学、血气、MetHb含量及NN组mPAP和PVR均无明显影响；HE染色光镜和透射电镜显示HC和HN组肺的组织学及超微结构均呈慢性缺氧改变，但未发现NN组较NC组、HN组较HC组之肺组织学和超微结构有明显恶化改变。提示短时吸入低浓度NO对降肺动脉高压具有选择性、安全及无毒副作用等特点。     

Pharmacodynamic profile of short-term readministration of abciximab in healthy subjects

Objective The purpose of the study was to establish a rebolus regimen for abciximab that restores pharmacologic glycoprotein (GP) IIb/IIIa receptor blockade within a short time frame (up to 48 hours) after completion of an initial treatment. Methods and Results The study was a single-center, nonrandomized, open-label dose escalation trial in healthy volunteers (n = 30). Each subject received a 0.25 mg/kg bolus and a 0.125 μg/kg per minute infusion of abciximab, followed by incremental bolus doses of the agent at 15-minute intervals up to 48 hours (10 per group) after completion of the infusion, (maximal cumulative rebolus dose of 0.25 mg/kg). Pharmacodynamic measurements (GP IIb/IIIa receptor blockade, turbidimetric and whole blood platelet aggregation with use of a rapid platelet function assay [RPFA]) were obtained at periodic intervals during and after administration of the abciximab bolus and infusion. At the time of the first rebolus, pharmacodynamic measurements were attained immediately before administration of each rebolus and 15 minutes after the last rebolus dose. In subjects who received reboluses 12 hours after infusion, a cumulative dose of 0.05 mg/kg restored >80% blockade of GP IIb/IIIa receptors and >80% inhibition of turbidimetric (5 and 20 μmol/L adenosine diphosphate) and RPFA aggregation in 10 of 10 subjects. At 24 hours after treatment, a cumulative abciximab bolus dose of 0.1 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. At 48 hours after treatment, a cumulative bolus dose of 0.15 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. Conclusions A fraction of the bolus of abciximab restored pharmacologic (>80%) GP IIb/IIIa receptor blockade when readministered at various postinfusion time points. These observations suggest that in the setting where acute readministration of abciximab is required less than a full bolus dose of the agent is warranted. (Am Heart J 2002;143:87-94.)     

Excessive bronchoconstriction induced by histamine and effects of volume history in patients with bronchial asthma

Abstract The aim of this study was to examine the inter-relationships between the different effects of deep breaths and histamine provocation on airway function in patients with bronchial asthma. Group 1 consisted of 38 consecutive out-patients with newly diagnosed mild asthma, group 2 consisted of 20 patients with bronchial asthma of varying severity who were studied during clinical remission. We measured bronchial responsiveness (BR) to histamine inhalation as the dose of histamine which provoked a 20% fall in FEV₁ (PD₂₀). The fall in forced vital capacity (FVC) after inhaling the highest dose of histamine during each BR test was calculated and expressed as percentage of the value measured at baseline (δFVC in percentage). We studied the effects of deep breaths on airway caliber in group 2 patients by comparing isovolumic flow rates on partial (P) and maximal (M) forced expiratory flow volumes curves expressed as the M/P ratio. The changes in residual volume (RV) after deep breaths (δRV) were expressed as a percentage of the largest VC measured on the composite M and P curves. The patients in group 1 had significantly higher PD₂₀ and lower δFVC than patients in group 2. There was, however, no significant correlation between PD₂₀ and δFVC measurements in individual patients (r<0.1, P>0.05). The M/P ratio was significantly related to δFVC (r=?0.6, P<0.006). There was also a significant positive relation between the magnitude of increase in residual volume following deep breaths (δRV) and the degree of fall in FVC following histamine inhalation (δFVC) (r= 0.65, P= 0.001). This significant relationship between the degree of airway closure after a deep breath and airway closure after histamine challenge is a new finding. In patients with bronchial asthma, the effects of a deep breath on airway function may be indicative of the tendency for airway closure during BR testing.     

Capsaicin-induced cough in humans.

We have evaluated the properties of capsaicin as a selective cough-inducing agent in healthy human subjects. Despite frequent coughing, the subjects could inhale repeated breaths of capsaicin aerosol during 60 s without difficulty. Cough started immediately on inhalation and was most intense during the first 30 s. Cough always disappeared promptly when the capsaicin inhalation was terminated. The cough response was well reproducible and concentration-dependent up to 10 microM; at higher concentrations there was a distinct plateau of the cough response. Specific airway conductance was not changed 3 min after 50 microM capsaicin. Capsaicin (> or = 10 microM) had a burning taste, but there were no visual signs of pharyngitis or laryngitis. Citric acid (nebulized solutions 0.125 to 32%) had a choking effect and could be administered only as single breaths. There was no correlation between the cough response to citric acid and to capsaicin. Inhaled lidocaine (20 and 80 mg from nebulized solutions) caused a dose-dependent inhibition of capsaicin-induced cough. Lidocaine suppressed citric acid-induced cough as effectively as capsaicin-induced cough. In conclusion, we have characterized capsaicin-induced cough and demonstrated that it can be a useful tool in the study of cough reactivity and for evaluation of antitussive agents in humans. Capsaicin may be complementary to citric acid and may offer experimental advantages over this traditional tussive stimulus.     

Subjective Effects of Two Anorexigenic Agents Fenfluramine and AN 448 in Amphetamine-Dependent Subjects

Twenty-two amphetamine-dependent subjects, all imprisoned drug abusers, with a history of at least one year of intravenous abuse of central stimulants, were used for evaluation of the subjective effects of the two weight-reducing drugs fenfluramine and AN 448. During four different days, each subject received a single dose of the following drugs in a double-blind study with cross-over design: AN 448 2 mg, fenfluramine 80 mg, amphetamine 50 mg and placebo. A self-rating scale for the factor “CS effect” was used before drug intake, and 1, 3 and 6 hours thereafter. A question of “similarity to amphetamine” was posed at 6 hours after drug intake. Some subjects experienced a low degree of amphetamine-like effect from AN 448, whereas no such effect was found for fenfluramine. With regard to the factor “CS effect”, AN 448 and fenfluramine did not differ from placebo.     

Nonspecific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in subjects with respiratory symptoms of uncertain etiology

Fifty adult subjects referred to a respiratory function laboratory of a tertiary care hospital for respiratory symptoms of uncertain etiology were investigated prospectively by means of a questionnaire, isocapnic inhalation of dry cold air (-20 degrees C), histamine inhalation tests, monitoring of peak expiratory flow rates, total eosinophil counts, and total IgE. Wheezing, tightness in the chest, dyspnea, and cough were reported by 35, 23, 41, and 30 subjects, respectively. FEV1 values less than 80% pred were found in only 2 subjects. Twenty-nine subjects had a PC20 histamine less than or equal to 16 mg/ml. Twenty, 15, and 10% falls in FEV1 were found in 10, 18, and 26 subjects, respectively, using hyperventilation of cold air. Significant eosinophilia and increased total IgE levels were seen in 5 and 18 subjects, respectively. Eight subjects had daily changes in PEFR greater than 20% on at least 1 day of monitoring. There was no significant association between specific responses to the respiratory questionnaire or the presence of rhinitis on the one hand and bronchial responsiveness to histamine and cold air on the other hand. The 10 subjects who demonstrated a greater than 20% change in FEV1 after cold air inhalation also had a PC20 less than 16 mg/ml, and 5 of them reacted at a concentration less than or equal to 2 mg/ml. Two subjects who had a PC20 less than or equal to 2 mg/ml demonstrated a less than 20% change in FEV1 after inhaling cold air. There was no association between the increase in total eosinophils or IgE and bronchial hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomised trial of insulin on well-being and carer strain in elderly type 2 diabetic subjects

INTRODUCTION: Selected tablet-treated elderly type 2 subjects with very poor glycaemic control may experience improvements in well-being after starting twice-daily insulin. In this study, the health status, mood, and treatment satisfaction of diabetic subjects with poor control on oral medication were assessed before and after being randomised to one of two insulin regimens. METHODOLOGY: Fifty-seven type 2 subjects with poor glycaemic control (HBA(1c) 9.7%) were randomised to continue tablets (Group l), twice-daily isophane insulin (Group 2), or basal/bolus isophane/lispro insulin (Group 3). Health status, treatment satisfaction, and mood were measured at baseline, 1, 3, and 6 months. RESULTS: Mean HBA(1c) levels were lower in Groups 1 and 3 at 6 months (P<.02 and.03, respectively) but not Group 2 (P=.2). Mean health status scores did not differ between the groups at any time point. In Group 3, significant within-subject improvements occurred in six domains of the SF-36 at 1 month, four domains at 3 months, and six domains at 6 months. There were no significant within-subject changes in health status scores in the other groups. Mean anxiety scores improved in both Groups 1 and 3 over 6 months, and mean depression scores also improved in Group 3 during the study. CONCLUSIONS: Small improvements in health status and mood may be associated with basal/bolus, but not twice-daily, insulin in elderly type 2 subjects. These effects may be independent of glycaemic control.     

Healthy subjects with a family history of alcoholism show increased stimulative subjective effects of alcohol

Background: Research has shown that subjects with a family history positive (FHP) of alcoholism are at increased risk for alcoholism and that this group reacts differently to alcohol than family history negative (FHN) subjects. These different levels of sensitivity may make FHP persons more likely to consume alcohol. Here, we tested the hypothesis that subjects FHP for type 1 alcoholism (according to Cloninger) are more sensitive than control subjects to the stimulative, properties of alcohol following a single moderate dose of alcohol. Methods: Fifty‐one healthy men and women (22 FHP and 29 FHN) participated in 2 laboratory sessions, in which they consumed a beverage containing ethanol (0.6 g/kg in juice) or placebo (juice alone) in a randomized order. Primary dependent measures were self‐report questionnaires of mood states. Results: Subjects with family history of type 1 alcoholism showed increased stimulative responses and an elevated positive mood state after ethanol compared to controls. Conclusions: At this moderate dose, ethanol increased stimulative subjective responses in individuals who were “family history positive.” This enhanced sensitivity could motivate to exaggerated drinking and thereby increase the risk for developing alcoholism.     

Dose Dependence and Time Course of Smoke Inhalation Injury in a Rabbit Model

The dose dependence and time course of smoke inhalation injury were determined in a rabbit model. Animals were insufflated with 18–90 breaths of cotton smoke or room air (control) at a rate of 18 breaths/min and tidal volume of 12 ml/kg. Smoke-exposed animals exhibited dose-related histologic effects with progressive deterioration of respiratory function during the postexposure period of observation (96 h). The smoke-exposed rabbits had reproducible injuries to both airway mucosa and lung parenchyma, manifested by disruption and sloughing of airway and alveolar epithelia, and exudation of protein-rich fluid and leukocytes into the airway and alveolar spaces. Significant effects were evident by 24 h postexposure. Smoke inhalation also affected the respiratory burst of alveolar macrophages. Generation of superoxide anions by alveolar macrophages at 48 h postexposure was increased significantly after smoke inhalation (54 breaths). The present rabbit model should be useful for studying the interactions between pulmonary epithelial cells and leukocytes after smoke inhalation and for determining the role that abnormal functioning of alveolar macrophages plays in the development of smoke inhalation injury. Accepted for publication: 8 October 1998