Comparative effects of carbamazepine, phenytoin, diazepam and clonazepam on inhibitory avoidance learning in mice. Four antiepileptic drugs were investigated in an inhibitory avoidance task in mice. Following IP administration 30 min prior to training, carbamazepine (32 mg/kg), phenytoin (30-60 mg/kg), diazepam (2-8 mg/kg) and clonazepam (0.125-0.5 mg/kg) impaired retention. When administered 30 min prior to the retention test none of the drugs under investigation affected retention. The drugs did not affect latencies in the hot plate test. This indicates that in the case of pretraining drug administration effects on retention cannot attributed to elevated pain thresholds. Carbamazepine and phenytoin impaired avoidance learning at doses above those which prevent electroshock induced tonic hindlimb convulsions. Diazepam and clonazepam were effective at lower than anticonvulsant doses. The results of the study are relevant to the evaluation of CNS side effects of anti-epileptic drugs in mice.


Differential ethanol intake in Tryon maze-bright and Tryon maze-dull rats: implications for the validity of the animal model of selectively bred rats for high ethanol consumption. The search for a genetically based "animal model of alcoholism" has led to the creation of extensive research programs using various combinations of initial ethanol preference screening techniques and breeding methods to yield rodents with primary genetic differences that contribute to high or low ethanol preference. The present experiment examined the ethanol intake of the Tryon rat strain, which were bred for high and low maze learning scores. It was observed that the Tryon Maze Bright rats displayed an unprecedented affinity for ethanol with stable intakes between 12.7 and 13.7 g/kg per day and preference ratios exceeding 0.75 for ethanol concentrations ranging between 15 and 29%. The pattern of ethanol intake of the Tryon Maze Dull rats resembled the ethanol intake pattern of other, non-selectively bred strains of rats, approximately 2-3 g/kg of absolute ethanol at preference ratios between 0.11 and 0.28. The affinity for ethanol observed for the Tryon Maze Bright rats seems to exceed the reported consumption patterns of rat strains specifically bred for high ethanol consumption although the Tryon rats were selectively bred for variables that were seemingly unrelated to ethanol intake.


Dopamine and endogenous opioid regulation of picrotoxin-induced locomotion in the ventral pallidum after dopamine depletion in the nucleus accumbens. Microinjection of picrotoxin or the mu-opioid agonist, Tyr-D-Ala-Gly-NmePhe-Gly-OH (DAMGO), into the ventral pallidum (VP) produces an increase in locomotor activity that is antagonized by dopamine receptor blockade. To investigate the regulation of VP-induced locomotion by the dopaminergic innervation of the nucleus accumbens (NA) and the role of opioid receptors in this regulation, dopamine innervation of the NA was bilaterally lesioned with 6-hydroxydopamine (6-OHDA). The lesions resulted in an 89-97% depletion of tissue dopamine levels in the nucleus accumbens compared with sham-lesioned rats. Dopamine depletion in the NA failed to significantly antagonize picrotoxin or DAMGO injected into the VP. However, the dopamine receptor antagonist, haloperidol (0.1 mg/kg, IP), blocked the picrotoxin-initiated increase in horizontal photocell counts in both sham- and 6-OHDA-lesioned rats. The opioid receptor antagonist, naloxone (1.0 mg/kg, SC), also blocked the picrotoxin-induced locomotion in 6-OHDA-lesioned rats but did not block locomotion in the sham-lesioned rats. At a higher dose (3.0 mg/kg, SC), naloxone blocked picrotoxin-induced locomotion in both sham- and 6-OHDA-lesioned rats. These results indicate that although dopamine depletion in the NA does not affect the permissive role of dopamine transmission on locomotion elicited from the VP, it results in an increased sensitivity to enkephalinergic transmission.


Pharmacological dissociation between the spatial learning deficits produced by morphine and diazepam. This study sought to determine whether the place learning deficits produced by diazepam are a secondary result of opioid release. Rats pretreated with diazepam (3 mg/kg) or morphine (15 mg/kg) were trained in the Morris water maze. Diazepam impaired place learning-slowing acquisition and preventing the formation of a quadrant preference. Morphine also slowed acquisition, but did not prevent place learning, and impaired escape to a visible platform. Flumazenil blocked the deficits produced by diazepam, but not morphine. Naloxone (2 mg/kg) blocked the deficits produced by morphine, but not diazepam. A high dose of naloxone (10 mg/kg) slowed acquisition, and exacerbated the deficit produced by diazepam. These results demonstrate that diazepam interferes with mnemonic processes through endogenous benzodiazepine receptors, independently of opioidergic systems. Further, they suggest that morphine interferes with motivational processes through opioidergic systems, independently of endogenous benzodiazepine systems.


Serotonergic function and late luteal phase dysphoric disorder. Thirty-eight subjects who met criteria for the DSM-III-R diagnosis late luteal phase dysphoric disorder (LLPDD) were compared with 18 controls in 5-HT uptake kinetics of the platelets in the premenstrual (day 26) as well as in the postmenstrual phase (day 4) of the cycle. Furthermore, 5-hydroxytryptophan (5-HTP) was administered to LLPDD patients and controls in both phases of the cycle, to investigate pituitary sensitivity for serotonin. Plasma samples for the measurement of cortisol and beta-endorphin were taken before and after oral administration of 200 mg 5-HTP, and considered as an index of pituitary-adrenal function. LLPDD was not associated with a lower platelet 5-HT uptake and content in the premenstrual phase of the cycle, compared with the postmenstrual phase. Patients appeared not to be different from controls in 5-HT uptake kinetics of platelets in the premenstrual phase of the cycle. No main differences were observed between LLPDD patients and controls in their ability to respond with secretion of cortisol and beta-endorphin to 5-HTP stimulation, either in the premenstrual, or in the postmenstrual phase. This observation could not be attributed to differences in 5-HTP metabolism. The findings of the present study do not support a specific role for 5-HT in the pathophysiology LLPDD.


Differential effects of early stimulation and/or perinatal flumazenil treatment in young Roman low- and high-avoidance rats. The effect of infantile handling-stimulation and/or perinatal flumazenil (3.7 mg/kg/day) administration on exploratory and emotional-related behavior was investigated using Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats. Postnatal handling increased exploration in 30-day-old rats of both psychogenetically selected lines when they were exposed to a hexagonal tunnel maze including an illuminated central arena. Likewise, postnatal stimulation decreased emotional reactivity in both lines of rats, as expressed by increased entry into the central arena, decreased defecation and vocalization frequency, but these effects were more pronounced in the RLA/Verh line. There were interactions between perinatal flumazenil treatment and rat line, indicating that flumazenil enhanced entry into the maze central arena in handled-RLA/Verh rats, whereas a tendency toward the opposite effect was observed in drug-treated and handled-RHA/Verh animals. Thus, the present study emphasizes that the effects of environmental manipulations are partly dependent upon genetic factors, and that pharmacological effects also depend on both genetic and environmentally-induced predisposition.


Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. Systemic administration of dopamine (DA) agonists markedly disrupts sensorimotor gating in rats as measured by prepulse inhibition (PPI) of the acoustic startle response. A qualitatively similar, but quantitatively weaker disruption of PPI follows DA infusion into the nucleus accumbens (NAC). The present study was designed to determine whether forebrain DA terminal fields other than the NAC contribute to the DAergic modulation of PPI. PPI was impaired significantly after infusion of DA (0-40 micrograms) into the NAC or anteromedial striatum, but not after DA infusion into the orbital cortex or posterolateral striatum. DA infusion into the amygdala also disrupted PPI, but this disruption was accompanied by a dose-dependent decrease in startle amplitude. These results suggest that DA overactivity in the both NAC and anteromedial striatum contribute to the gating-disruptive effects of systemically administered DA agonists, and that DA overactivity in mesocortical, mesoamygdaloid and "non-limbic" mesostriatal DA systems are not major substrates for a DAergic modulation of PPI.


Age-related changes in serotonin 5HT2 receptors on human blood platelets. Serotonin receptors of the 5HT2 type were labeled on platelet membranes using tritiated ketanserin. Blood was collected from the umbilical cord of newborns and venous samples were collected from 6-year-old children as well as junior-high and high school students (ages 13 through 18) to determine age-related changes in receptor binding. Among the ages sampled, the highest levels of 5HT2 receptor binding were found in 6-year-olds. A sharp decline in receptor binding occurred during adolescence, with levels reduced by half between ages 13 and 17. This pattern is similar to the one we have observed in brain 5HT2 receptors postmortem. There were no significant sex differences in 5HT2 receptors on platelets in newborn and young children. A trend towards higher binding in girls appears around the onset of menstruation in teenage girls (age 14 and up). These results demonstrate that platelet 5HT2 receptors can serve as a model for age dependent changes in 5HT2 receptors in the brain.


Absence of withdrawal effects of ritanserin following chronic dosing in healthy volunteers. The possible development of withdrawal symptoms following abrupt discontinuation of ritanserin after chronic administration of 10 mg daily for 8 weeks was investigated in a placebo controlled trial in 40 healthy subjects. The study consisted of two phases. In the first phase, under single blind conditions, all subjects received placebo for 2 weeks followed by a single daily dose of ritanserin (10 mg) for 8 weeks. In the second phase, under double blind conditions, subjects were randomised to receive either placebo or to continue on ritanserin (10 mg) for a further 4 weeks. Psychological assessments were performed at the start of and at intervals throughout the study. Levels of anxiety, concentration, quality of sleep and morning vigilance were measured throughout by daily visual analogue scales. No significant changes were detected in any of the measures in the group of subjects who received ritanserin compared to the group who received placebo during the second phase of the study. Ritanserin discontinuation following chronic dosing in healthy volunteers does not appear to be associated with withdrawal symptoms.


Effect of m-chlorophenylpiperazine on plasma arginine-vasopressin concentrations in healthy subjects. It has been demonstrated convincingly that ACTH and prolactin release are under the stimulatory control of serotonin (5-hydroxytryptamine, 5HT). Recent animal studies suggest that stimulation of 5HT activity also induces the release of arginine-vasopressin (AVP). More specifically, m-chlorophenylpiperazine (MCPP), a 5HT agonist widely used to examine 5HT receptor responsivity in human subjects, has been found to induce AVP release in rodents. This study examined whether MCPP increased plasma AVP levels in healthy human subjects. MCPP was administered orally to 17 healthy subjects in a placebo-controlled design in doses of 0.25 and 0.5 mg/kg. AVP was measured twice hourly over a 210 min period after administration of capsules. MCPP did not significantly alter AVP levels as compared to placebo. However, female subjects had significantly lower plasma AVP levels than males. Since it has been suggested that MCPP-induced AVP release in animals is due to stimulation of 5HT1c receptors, the fact that MCPP did not induce the release of AVP in humans suggests that either MCPP is not a potent 5HT1c agonist or that AVP is not released by stimulation of 5HT(1c) receptors in human subjects. The observation of gender differences in plasma AVP levels suggests that this factor should be taken into account in future studies of AVP secretion in plasma.


Tolerance to nicotine following chronic treatment by injections: a potential role for corticosterone. C57BL/6 male mice were injected intraperitoneally with nicotine (2.0 mg/kg) or saline three times each day (0800 h, 1300 h and 1800 h) for a period of 12 days and then tested for nicotine tolerance using a series of behavioral and physiological tests. For each of these tests, animals that received chronic nicotine treatment were significantly less sensitive to nicotine challenge than were animals that received chronic saline treatment, as indicated by shifts to the right of dose-response curves. Animals were retested for nicotine sensitivity 2 weeks following cessation of chronic nicotine injections. Tolerance to acute nicotine challenge persisted in nicotine-treated animals. Chronic nicotine treatment by injections did not alter the binding of L-[3H]-nicotine or alpha-[125I]-bungarotoxin in any of eight brain regions. Plasma corticosterone (CCS) levels were determined in animals prior to the initiation of the injection series (day 0), and on days 4, 8 and 12 of chronic treatment, immediately before the first injection of the day. CCS levels in nicotine-treated animals were elevated as compared to saline-injected controls by day 12 of treatment. Nicotine-treated animals also had elevated CCS levels 2 weeks after the last chronic injection. Nicotine-treated animals were, however, tolerant to nicotine-induced CCS release. Since previous studies from our laboratory have demonstrated that plasma CCS levels are inversely correlated with sensitivity to nicotine, it is possible that the tolerance to nicotine measured following chronic treatment by injections is due, at least in part, to the elevation in plasma CCS levels.


The acoustic startle response as a measure of behavioral dependence in rats. A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05-0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in non-dependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4-5 days after implantation induced large startle-response decreases in morphine-dependent rats while having no effect in placebo-implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3-10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response.(ABSTRACT TRUNCATED AT 250 WORDS)


Caffeine tolerance and choice in humans. Thirty-two healthy subjects with histories of moderate caffeine consumption abstained from dietary caffeine throughout the study. Subjects were stratified into two groups based on several factors including caffeine preference, which was assessed using a caffeine versus placebo choice procedure. Subsequently, subjects received either caffeine (300 mg t.i.d.) or placebo (placebo t.i.d.) for 18 consecutive days, and thereafter were exposed again to a caffeine versus placebo choice procedure. The study documented tolerance development to the subjective effects of caffeine: after chronic dosing, administration of caffeine produced significant subjective effects in the chronic placebo group but not in the chronic caffeine group. The study also provided indirect evidence for tolerance development: during chronic dosing, the chronic caffeine and placebo groups did not differ meaningfully on ratings of mood and subjective effect. When subjects were categorized into caffeine choosers or nonchoosers, caffeine choosers tended to report positive subjective effects of caffeine and negative subjective effects of placebo. Nonchoosers, in contrast, tended to report negative subjective effects of caffeine. Chronic caffeine did not alter the reinforcing effects of caffeine as assessed by caffeine versus placebo choice, possibly because the relatively short duration of caffeine abstinence in the placebo condition was not sufficient to result in maximal withdrawal effects after termination of the relatively high caffeine dose. This study provides the clearest evidence to date of complete tolerance development to a CNS effect of caffeine in humans.


Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6-glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion.


Rebound insomnia in normals and patients with insomnia after abrupt and tapered discontinuation. Rebound insomnia was studied in subjects, aged 25-50 years, with insomnia complaints and normal sleep, insomnia complaints and disturbed sleep, and normal sleep with no complaints (N = 21, n = 7 per group). Standard sleep recordings were collected on a baseline night and after abrupt discontinuation of 6 nights of 0.50 mg triazolam, tapered discontinuation (3 nights of 0.50 mg, 2 nights of 0.25 mg, and 1 night of 0.125 mg triazolam) and 6 nights of placebo. Significantly disturbed sleep on the discontinuation night compared to the baseline night was found. The relative degree of rebound insomnia was greater in the abrupt condition than in either the tapered or placebo conditions. The tapered condition reduced sleep time by half that of the abrupt condition which was twice the reduction found in the placebo condition. An overall (regardless of group or condition) difference in baseline versus discontinuation sleep was found, suggesting that pill discontinuation itself leads to sleep disturbance. Subjects did not differ in rebound insomnia as a function of pre-existing sleep disturbance.


Reinstatement of heroin self-administration habits: morphine prompts and naltrexone discourages renewed responding after extinction. The effects of morphine, naltrexone, and nalorphine were studied in rats trained to lever-press for intravenous heroin and then tested under conditions of non-reinforcement. Animals were reinforced for lever-pressing on a continuous reinforcement schedule (100 micrograms/kg per infusion) for 2-3 h each day following which reinforcement was terminated and animals were studied under extinction conditions for the remainder of the session. Each day following the termination of responding under extinction conditions, animals were given a single injection of saline, morphine, nalorphine, or naltrexone; lever-pressing under the extinction conditions was then observed for several hours. When animals adapted to this regimen, very low levels of responding were seen following saline injections; morphine (2 or 10 mg/kg) reinstated vigorous responding that lasted 1-4 h. Naltrexone (2 mg/kg) suppressed responding below the levels seen after saline, and nalorphine (10 mg/kg) had the same effect as saline. These observations support the view that opioid-seeking behavior is primed by the proponent or opioid-like actions of opioids and not by the opponent or drug-opposite effects associated with opioid withdrawal.


Serotonergic function during lithium augmentation of refractory depression. Serotonergic mechanisms have been implicated in the pathophysiology of depression and in the neuropharmacology of antidepressant treatment. One measure of central serotonergic function is the prolactin (PRL) response to IV L-tryptophan (L-TRP). We used the L-TRP test to assess the role of serotonin in the mechanism of action of lithium augmentation in refractory major depression. Twenty-six patients with antidepressant-refractory major depression each received three L-TRP tests (after 2 weeks of placebo, after 4 weeks of active primary antidepressant, and after 1 week of lithium augmentation). Primary antidepressant treatment did not increase the PRL response, but lithium augmentation resulted in a statistically significant increase in PRL response as compared to both placebo pretreatment (P less than 0.04) and antidepressant treatment alone (P less than 0.025). This study supports a role for serotonergic mechanisms in the action of lithium augmentation.


Nicotine issues.

Nicotine issues. This issue has covered most of the important concerns of nicotine researchers. Inevitably, there are gaps, because the selection of papers could only cover those which had been submitted or were known to be in preparation and about to be submitted. Nevertheless, these articles should serve to stimulate further discussion of and investigation into all aspects of nicotine use.


The role of nicotine in tobacco use.

The role of nicotine in tobacco use. The 1988 US Surgeon General's Report titled "Nicotine Addiction", is cited frequently in the literature as having established the "fact" that nicotine derived from cigarette smoke is addictive in the same sense as "classic" addicting drugs such as heroin and cocaine. This manuscripts critically evaluates key research findings used in support of this claim and identifies shortcomings in the data that seriously question the logic of labeling nicotine as "addictive". In addition, the manuscript argues that the role of nicotine in tobacco use is not like the role of cocaine in coca leaf use as argued by the 1988 Surgeon General's Report, but is, in fact, more like the role of caffeine in coffee drinking as concluded in the 1964 US Surgeon General's Report.


Nicotine addiction: a re-analysis of the arguments. This paper evaluates the arguments put forward by Robinson and Pritchard (R&P, this volume) that the conclusions of the US Surgeon General (USDHHS 1988) that nicotine is addictive were ill founded. R&P state that nicotine does not cause intoxication, that many smokers do not exhibit compulsive use, that nicotine is not a euphoriant, that nicotine is a weak reinforcer in other species, that non-pharmacological aspects of smoking are important and that negative affect control accounts for more of the variance in questionnaire measures of smoking motives than does habit. This paper points out that intoxication and a euphoriant effect are not normally considered to be central to dependence potential, that no addictive drug results in compulsive use in all users in all situations, that animals do reliably self-administer nicotine, that evidence concerning the apparent importance of non-pharmacological components of smoking do not diminish the importance of pharmacological aspects and that "variance accounted for" of self-report measures of smoking motivation do not bear on the issue of the importance of those motives. The paper concludes with a summary of the essence of the argument that cigarettes are addictive and that nicotine is the primary focus of that addiction.


Psychomotor performance in smokers following single and repeated doses of nicotine gum. The psychomotor effects of single and repeated doses of 2 mg nicotine gum were investigated in 13 regular smokers who had abstained from tobacco overnight. In comparison to baseline, a first dose of nicotine led to significantly raised critical flicker fusion thresholds, faster motor reaction times, improved compensatory tracking performance, and faster short-term memory reaction times. Performance after a second and third dose of nicotine remained significantly improved on all measures in comparison to baseline, and absolutely improved when comparing first and third nicotine doses on measures of sensorimotor performance. Throughout, comparisons with a placebo gum condition confirmed that these effects were genuine and not subject to the development of acute nicotine tolerance, suggesting that the enhancement of psychomotor performance experienced by smokers after a first cigarette may be maintained by repeated smoking.


Enhancement of continuous performance task reaction time by smoking in non-deprived smokers. In a test of the withdrawal-deficit hypothesis of the cognitive effects of cigarette smoking, non-deprived smokers participated in two sessions held on consecutive days. In both sessions, subjects performed two 20-min continuous performance tasks (CPTs). The CPT was a relatively "easy" version designed to require minimal practice (digit 0 target response; digits 1-9 nontarget response; 19% of stimuli targets). In one session, subjects smoked a cigarette prior to each CPT; in the other session they did not smoke (session order counterbalanced). Reaction time (RT) was significantly faster in the smoking session than in the non-smoking session with no difference in number of incorrect responses, a finding incompatible with the withdrawal-deficit hypothesis. Further, light inhalers (as assessed by pre-smoking to post-task increase in expired air carbon monoxide) appeared to process nontarget stimuli faster than deep inhalers, especially in the no smoking session. The results also indicated that, at least during the first CPT of each session, the performance of females in the no smoking session was poorer than in the smoking session and poorer than males regardless of session. In the latter part of the first CPT, the performance of males in the smoking session was better than their performance in the no smoking session. No clear pattern emerged for the second CPT.


A comparison of the attentional and consolidation hypotheses for the facilitation of memory by nicotine. Studies examining facilitation of human memory by the administration of nicotine have given equivocal results and it has been argued that the positive findings on memory may have resulted indirectly from an effect on attention, rather than from a direct effect on memory storage. This study compared the "attentional" and the "mnemonic" hypotheses directly, by using both immediate and delayed recall tasks in a verbal free recall study, in which volunteers smoked on a fixed regime during presentation of a 32 word list (namely, one puff after each of eight 4-word blocks). The serial position curve for immediate recall demonstrated a significant improvement on the later blocks of the list (an attentional effect) when volunteers smoked a nicotine-containing cigarette. However, improved performance was found for items at the beginning of the list on the delayed recall measure and this improvement was significant on the first block of 4 words. Since nicotine input had been taken after presentation of this information, the results demonstrate post-learning facilitation of memory by nicotine.


Effects of post-learning smoking on memory consolidation. The effects of immediate post-learning smoking of low and medium nicotine delivery cigarettes were compared to those of smoking a denicotinised cigarette and a no-smoking control condition in a paired-associate learning task. Thirty-nine male smokers were tested for retention of the memorised material at 1 week post-learning. All subjects received all conditions in a repeated measures design. The low nicotine condition was associated with significantly fewer errors on first trial of recall and fewer total errors to criterion. There were no differences in performance reported between the no-smoking and zero nicotine conditions. The medium nicotine condition produced results part way between the no-smoking and low nicotine conditions. Results are discussed in terms of the effects of nicotine on long-term consolidation mechanisms.


Facilitation of memory by post-trial administration of nicotine: evidence for an attentional explanation. In human studies, reported performance improvements with post-trial administration of nicotine have all involved associative learning (Mangan and Golding 1983; Colrain et al. 1992; Warburton et al. 1992). In this study, post-trial nicotine, obtained through smoking a cigarette, improved free recall of lists of unrelated words under conditions which limited the opportunity for associative learning. However, the nicotine-induced advantage was not observed when volunteers were required to complete a secondary (attention) task during the post-trial period in which they smoked. The results suggest that post-trial effects depend on the opportunity for stimulus processing after input, and that nicotine improves performance by increasing the attentional resources available for such strategic processing.


Function of cigarette smoking in relation to examinations. Eighty-two college students took part in a study on motives underlying increases in cigarette smoking prior to examinations. One group was tested a month before, and a second group was tested the day before, the start of examinations. Measures were taken of current cigarette consumption, general anxiety, anxiety about forthcoming exams, the importance of sedative and stimulant smoking motives, hours spent revising and in other activities and amounts smoked during these activities. The results indicated that the students increased the hours they spent revising and there was a corresponding increase in the number of cigarettes smoked during this activity. They also reported an increase in the importance of stimulant smoking motives. Anxiety levels increased in the run up to exams but there was no increase in sedative smoking motives. The results raise the issue of whether any anxiolytic action of nicotine may be limited to acute stressors and also whether smokers' use of cigarettes to help them stay alert during revision translates into improved examination performance.


Euphoriant effects of nicotine in smokers. Two studies were conducted to replicate and extend previous demonstrations of smoking-induced, dose-related reports of euphoria, and to confirm this relationship using measures of plasma nicotine. In experiment 1, overnight-deprived subjects, in three different sessions, smoked ultralow-, high-nicotine, and usual-brand cigarettes. In experiment 2, ultralow-, medium-, and high-nicotine cigarettes were used, and plasma nicotine was measured. In both studies, subjects were asked to depress a button during euphoric sensations. Number of sensations for the ultralow-nicotine cigarette was significantly lower than for the high-nicotine cigarette in the first study, and than for both the medium- and high-nicotine conditions in the second; a significant linear trend was observed for number of sensations as a function of plasma nicotine level in the second study. For the high-nicotine cigarette, 19 of 22 subjects experienced at least one sensation (mean around three), starting around 2.5 min after lighting up. Together, these studies support the existence of a dose-response relationship for nicotine-induced euphoric sensations; suggest that they are more pronounced following overnight abstinence than following minimal deprivation, and in more dependent smokers; and characterize in detail the temporal features of these sensations.


Psychopharmacological effects of smoking a cigarette with typical "tar" and carbon monoxide yields but minimal nicotine. Five male smokers were tested, after 48-h abstention from tobacco-product use, smoking a leading "lights" category cigarette (Control-FTC nicotine yield 0.6 mg) and another cigarette yielding similar amounts of "tar" and carbon monoxide (CO), but only 0.06 mg nicotine (Test). Heart rate (HR) and the electroencephalogram (EEG) were monitored before, during and after the smoking of each cigarette. Other measures obtained included the subjects' puffing and breathing behaviors during smoking, plasma nicotine concentrations, blood carboxyhemoglobin concentrations and expired-air CO. The results indicated no significant differences in the way the subjects puffed and inhaled the two cigarettes and they were therefore assumed to have inhaled similar amounts of particulate matter and gas-phase components. Plasma nicotine concentrations were significantly higher following smoking of the Control cigarette. HR (percent relative change) increased following smoking of either cigarette; however, HR increase was significantly greater following smoking of the Control cigarette. Smoking the Test cigarette had no effect on the EEG. Smoking the Control cigarette produced a significant increase in beta 2 magnitude and a significant decrease in delta magnitude. This indicates that the effects of smoking on the EEG are a function of nicotine absorbed from cigarette smoke upon inhalation and not a function of inhaled particulate matter, CO, or other gas-phase components.


Smoking, nicotine dose and the lateralisation of electrocortical activity. The effects of cigarette smoking on the balance of activity of the cerebral hemispheres were studied in two experiments. Experiment 1 examined the effects of smoking on lateralisation of EEG alpha and beta power in six male smokers, and revealed a dose-related biphasic action. Low doses of nicotine as measured by residual butt analysis increased left hemisphere activity in a dose related manner, while higher doses (greater than 1.1 mg) reversed this effect. Experiment 2 examined the time course of the changes in EEG alpha, beta, theta and delta lateralisation in 11 male smokers. During the initial period of smoking there was a reduction in EEG alpha, reflecting cortical activation, followed by an increased in alpha power towards the end of the cigarette. These changes were accompanied in smokers taking moderate nicotine doses, by an initial shift towards left hemisphere activation, followed by a reduction in left hemisphere activation relative to the right. Initial changes in delta and theta power were negatively correlated with nicotine dose. Higher nicotine doses were associated with greater shifts towards right hemisphere activation, as indicated by beta and delta lateralisation, and also with greater decreases in subjective arousal. These results were interpreted as supporting the hypothesis that the stimulant action of lower doses of nicotine involves the activation of a left hemisphere "Go" system, while the sedative effect of higher doses involves increased activation of the right hemisphere "NoGo" system.


Acute nicotinic blockade produces cognitive impairment in normal humans. Single oral doses of the central and peripheral nicotinic antagonist mecamylamine were administered to healthy young normal males in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. The 20 mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition task, producing a slower acquisition curve. The lower doses produced less errors, but more than in the placebo condition. There was no effect of drug on the performance component (retrieval of previously learned information). On the recognition memory task, dose-related increases in false-alarms during the delay period were seen, with little effect on misses or hits. Reaction time measures suggested a dose-related slowing of RT on several tasks. Behavioral effects were minimal and physiologic measures were consistent with dose-related ganglionic blockade. We interpret these results to indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment, even in non-smoking normals.


Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. This single-blind, placebo controlled study reports on the effects of administering three acute doses of nicotine (0.4, 0.6 and 0.8 mg) subcutaneously to a group of Alzheimer's disease (DAT) patients (n = 22), young adult controls (n = 24), and normal aged controls (n = 24). The study extends our previous findings obtained using smaller groups of subjects. Drug effects were examined on three computerised tests: the first measuring rapid visual information processing, sustained visual attention and reaction time (RVIP task); a delayed response matching to location-order task measuring sustained visual attention and visual short-term memory (DRMLO task); and a finger tapping test measuring simple reaction time (FT task). The critical flicker fusion test (CFF) was used as a measure of perception and the WAIS digit span forwards (DS), of auditory short-term memory. Tests were graded in difficulty, titrated to avoid floor and ceiling effects so that meaningful, direct comparisons between groups could be made. Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task--both ascending and descending thresholds). Nicotine administration did not improve auditory and visual short-term memory. There were no consistent, overall patterns of difference in performance between smokers and non-smokers in the control groups, or between males and females in any group. Despite the absence of change in memory functioning, these results demonstrate that DAT patients have significant perceptual and visual attentional deficits which are improved by nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Experimental model of smoking re-exposure: effects on relapse. This study used a short-term laboratory model of smoking cessation and relapse to prospectively examine the effects of programmed self-administered smoking re-exposure during early abstinence. Sixty-seven subjects who had quit smoking for 3 days were randomly assigned either to smoke five cigarettes in their natural environment or to remain abstinent during the exposure period. The main hypothesis, that relapse to regular smoking would be quicker and more prevalent in exposed subjects, was supported. All exposed subjects had relapsed by 2 days post-exposure while 16% of unexposed subjects remained continuously abstinent throughout the 8 day study. This behavioral effect was seen in spite of acute decreases in reported desire to smoke and increases in guilt measured just after exposure. The study supports a role for stimulus re-exposure effects in the relapse process and suggests that additional research on experimental re-exposure is warranted.


Use of phenylpropanolamine to reduce nicotine cessation induced weight gain in rats. The present study was conducted to determine if phenylpropanolamine (PPA) administered during the first week of nicotine termination could reduce or eliminate the body weight rebound which accompanies nicotine cessation. Sprague-Dawley rats were administered nicotine for 2 weeks after which they received either PPA or saline for 1 week. Control animals received saline during both drug periods. Body weight, food consumption, and water consumption were measured daily before drug, during nicotine and PPA administration, and for 14 days after PPA administration. In contrast to animals receiving saline upon termination of nicotine, animals receiving PPA did not gain weight at an accelerated rate. Termination of PPA did not result in a body weight rebound. To the extent that these results generalize to humans, they suggest that PPA could be used to reduce or eliminate postcessation weight gain in smokers who stop smoking.


Nicotine intake and dependence in Swedish snuff takers. Two studies examining nicotine intake in users of Swedish moist oral snuff are reported. Absorption form a single pinch (2 g) in ten users after overnight abstinence was fairly rapid. The increment in plasma nicotine concentrations averaged 9.9 ng/ml (SD 6.5) after 10 min and peaked at 14.5 ng/ml (SD 4.6) shortly after discarding at 30 min. Among groups of habitual snuff takers (n = 27) and cigarette smokers (n = 35) studied on a day of normal snuffing/smoking, peak blood nicotine levels after use were similar [averaging 36.6 ng/ml (SD 14.4) and 36.7 ng/ml (SD 16.1), respectively], but there was a tendency to higher cotinine levels in the snuffers (399.2 ng/ml versus 306.3 ng/ml). The snuff takers and cigarette smokers reported similar levels of subjective dependence on tobacco. Epidemiological study of Swedish snuff users could clarify whether the cardiovascular risks of tobacco are attributable to nicotine or to other smoke components, as in their case nicotine intake is not accompanied by combustion products.


Nasal nicotine spray: a rapid nicotine delivery system. Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed.


Controlled dosing of nicotine via an Intranasal Nicotine Aerosol Delivery Device (INADD). The present report describes an Intranasal Nicotine Aerosol Delivery Device (INADD) employing an artist's airbrush as aerosolizer and precise, electromechanical control of spray duration. It was designed for the administration of controlled doses of nicotine in a laboratory setting and has been used successfully in over 30 smokers and nonsmokers of both genders. In the present study, nicotine was administered to 12 male smokers at three different doses (0.05 mg, 1.00 mg, and 2.00 mg), and at the same dose (1 mg) on three different occasions. The low dose produced a minimal change in plasma nicotine, while the high dose produced a peak increment of around 16 ng/ml. The medium dose reliably produced a peak increment of around 8-9 ng/ml on all three occasions. Nicotine in plasma showed a sharp rise followed by a slower decline, mimicking the pattern associated with cigarette smoking. Physiological and biochemical responses showed significant dose-response relationships. Subjective reports suggested that aerosol dosing was somewhat aversive, but it is unclear whether this effect is intrinsic to the method or due to other factors. The device described in this report answers the need for a safe and easy means of controlling nicotine dose. Moreover, since nicotine administration via aerosol is novel for both smokers and non-smokers, minimizing the contributions of behavioral tolerance and habituation to the dosing vehicle, it lends itself to the comparison of the pharmacological effects of nicotine between experienced and naive subjects.


Is it important that the mind is in a body? Inhibition and the heart. The hypothesis is advanced that certain inhibitory processes necessarily involve autonomic adjustments. Such adjustments would represent a constraint on information processing imposed by the location of the mind in a body. Evidence is reviewed showing that motoric inhibition is related to a transient delay in heartbeat generation. The delay is shown to further depend upon when inhibition occurs in the cardiac cycle. It is argued that this form of interaction between central and autonomic nervous system processing may be common. Central nervous system processes that may control inhibition and integrate information processing with motoric and autonomic processes are discussed.


Myocardial and peripheral vascular responses to behavioral challenges and their stability in black and white Americans. The purpose of this study was to assess the short term stability of myocardial and peripheral vascular responses to behavioral challenges, and to compare the response patterns of Black and White men. Blood pressure and heart rate, as well as stroke volume, cardiac output, total peripheral resistance, and systolic time interval measures derived from the impedance cardiogram were obtained in 12 Black and 12 White men. These measures were taken prior to and during an evaluative speech stressor, a mirror star tracing task, and a forehead cold pressor test presented during two laboratory sessions scheduled two weeks apart. In general, total peripheral resistance and impedance-derived baseline measures showed acceptable reproducibility (G greater than .85). With a few exceptions, adequate reliability was also demonstrated for change (delta) scores. All tasks raised blood pressure responses above resting levels. Blacks demonstrated significantly greater increases in total peripheral resistance responses across tasks. Whites but not Blacks also revealed increases above baseline in cardiac output and contractility as estimated by the Heather Index. These findings are consistent with the view that Blacks show greater vascular responsiveness than Whites across a variety of tasks, but reveal less myocardial responsiveness.


Mismatch detection and the latency of temporal judgements. Event-related potentials were recorded in two auditory tasks involving the discrimination of pitch or duration of binaurally presented tones. Frequently-presented nontarget tones, when compared to the same tones in a simple reaction time task, elicited two negative peaks, NA1 and NA2, followed by a positive peak, nontarget positivity. Infrequently-presented target tones, when compared to the nontargets, elicited mismatch negativity (MMN), followed by N2 and P3b. The peak latencies of NA1 and NA2 did not differ between the pitch and duration tasks, but the duration of NA1 and the peak latencies of mismatch negativity, N2, and P3b, as well as reaction time, increased in parallel for the duration task. It is proposed that the NA1-nontarget positivity sequence reflects the initiation, maintenance, and termination of an attention-modulated process, which is required for the performance of an auditory discrimination task, and that the MMN-N2-P3b sequence reflects a process elicited by infrequently-presented targets, which is the main determinant of reaction time under these testing conditions.


The chronometry of attention-modulated processing and automatic mismatch detection. Event-related potentials were recorded from normal subjects in an auditory selective attention task. Targets were rare longer (170-ms) tones of a designated pitch, embedded in a sequence of 100-ms standard tones. The effects of attention-modulated processing were evident in the event-related potentials elicited by the standards. Those to relevant standards were similar for easy (1000 Hz vs. 2000 Hz) and hard (1000 Hz vs. 1030 Hz) pitch separations, and were more negative frontocentrally than those to irrelevant standards. Difference waveforms (attended minus unattended standards) revealed Nd, a negative deflection that was earlier in latency for the easy task (onset, 120 ms; peak, 250 ms) than for the hard task (onset, 250 ms; peak, 350 ms). The speed of detection of the deviant longer tones was insensitive to the attention-modulated processes indexed by Nd. Median reaction time did not differ between tasks, although there were more misses and false alarms in the hard task (and nearly all of the latter were to the irrelevant longer tones). Neither direction of attention nor task difficulty affected the latency of mismatch negativity, N2, or P3 (as identified in difference waveforms: attended or unattended longer tones minus their respective standards). The data suggest that performance was guided by two independent but converging processes, automatic mismatch detection of the longer tone and attention-modulated processing of pitch, followed by selection of response.


Blushing as a function of audience size. Almost no experimental analysis of blushing has been done since Darwin's observations in 1872. Forty-eight college women watched a videotape intended to elicit blushing, and a videotape not intended to elicit blushing, but elicit physiological responses. A subject was alone, or with one or four persons present. Blushing, which was measured directly with a photoplethysmograph probe on the cheek, was greater during the blushing than nonblushing stimulation. Blushing increased as audience size increased from one to four, but not from zero to one. Audience size and kind of stimulation interacted statistically. Similar results were obtained with ear coloration, cheek temperature, and skin conductance responses, although confidence levels were lower. Cheek coloration and temperature were significantly correlated during nonblushing stimulation, and the zero and one audience conditions, but not during the four audience condition, when blushing was greatest. These results may be placed within the context of emotional effects of audience size generally, including stuttering and speech disturbance, disruption of learning, and self-reported tension.


Prestimulation-induced startle modulation in attention-deficit hyperactivity disorder and nocturnal enuresis. Startle modulation was induced by prestimulation in 43, 6-11 year old boys with attention-deficit hyperactivity disorder (ADHD), 13 of whom were or had been enuretic, 17 age-matched enuretic boys, and 42 age-matched normal boys, using 60-ms and 120-ms prestimulation intervals and a 4000-ms continuous tone. There was a significant multivariate effect of enuresis on startle amplitude modulation. This effect was attributed primarily to the reduction of amplitude inhibition following the 120-ms prestimulation interval regardless of whether or not enuresis was associated with ADHD. There was no effect of ADHD on startle modulation by prestimulation. The inhibition following the 120-ms prestimulation interval in the enuretic boys was reduced to the level of 5-year-old normal children, suggesting a maturational component of the deficient startle inhibition. The neurophysiologic dysfunction underlying the deficient startle inhibition in enuresis, but not ADHD, is discussed in terms of a possible dysfunction of mesopontine reticular mechanisms mediating preattentive processing of signals associated with spinal reflexes involved in urinary bladder control.


Symptom-specific psychophysiological responses in chronic pain patients. Symptom-specific psychophysiological responding was assessed in 20 chronic back pain patients, 20 patients suffering from temporomandibular pain and dysfunction, and 20 matched healthy controls. Surface EMG from the lower and upper back, the masseter, and the biceps muscles, and heart rate and skin conductance level were continuously recorded during adaptation, resting baseline, and stressful and neutral imagery phases. Univariate and multivariate analyses of variance were performed on raw data as well as data corrected for autocorrelation. The results showed significantly higher EMG reactivity which was lateralized to the left side at the patients' site of pain but not distal sites. This hyperreactivity was observed only during stressful imagery. The healthy controls displayed a significantly higher response in heart rate, but skin conductance level was not significantly different. The results are interpreted as indicative of idiosyncratic muscular response patterns to personally relevant situations at the site of pain in patients suffering from chronic muscular pain.


Respiratory sinus arrhythmia and cardiovascular responses to stress. The parasympathetic nervous system provides mechanisms that could attenuate sympathetically mediated heart rate stress responses and might have even more general antagonistic actions on stress reactivity. Individuals characterized by higher levels of parasympathetic tone might, through such mechanisms, be less reactive when stimuli elicit sympathetically mediated responses. Respiratory sinus arrhythmia (RSA) is considered to be a noninvasive index of cardiac parasympathetic (vagal) tone. The present study investigated whether individual differences in RSA level at rest could predict variations among individuals in the magnitude of cardiovascular responses to psychological stress. None of the measures of resting respiratory sinus arrhythmia, derived from spectral analysis of beat-to-beat changes in resting heart rate, predicted the observed variations in cardiovascular task reactivity. However, scores reflecting respiratory sinus arrhythmia as the percentage of total heart rate variability (RSAnorm) were negatively correlated with blood pressure levels, both at rest and during the task. Furthermore, subjects with higher scores for RSAnorm demonstrated a faster adaptation of heart rate responses during stress, which suggests the development of parasympathetic antagonism to ongoing sympathetic arousal. Although a simple relationship between respiratory sinus arrhythmia and reactivity was not observed, these results encourage further investigation of RSA measures as psychophysiological indices of individual differences in parasympathetic (vagal) cardiac tone, or perhaps of general parasympathetic/sympathetic balance, which could modulate the expression of potentially pathogenic stress responses.


Event-related potentials and the identification of deviant visual stimuli. The effects of deviant visual stimuli on event-related potentials were investigated in a counting task (Experiment 1) and in a reaction time task (Experiment 2). In Experiment 2 the interstimulus interval was either short or long (340 vs. 1020 ms). The stimuli (two angles within a frame) were frequent (Standard) or deviant (differing from the Standard either in the orientation of the two angles, or in the thickness of the frame, or in both of these features). In various conditions the target stimuli were defined by one of the deviant features or by the conjunction of these features. Subjects were more accurate in the counting task, and the reaction time was shortest when the target feature was the deviant angle orientation. Performance was lowest for the conjunction of the deviant features. The deviant angle orientation elicited a posterior negative wave in the 140-180 ms range. As the interstimulus interval increased, the magnitude of this component decreased. All stimuli with relevant (attended) deviant features elicited another posterior negative wave in the 180-260 ms range, as well as an anterior positivity with similar latency. When the interstimulus interval was short, and the only target was the Conjunction Deviant, the summed occipital activity to the relevant features of deviant nontarget stimuli was larger than the negativity to the Conjunction Deviant. Target stimuli elicited late positive waves, which were sometimes preceded by central negativity.


Recent developments in the study of cardiovascular reactivity: contributions from psychometric theory and social psychology. Two related ongoing research programs are described. The first examines optimal measurement strategies for assessing individual differences in cardiovascular reactivity, and the second investigates the effects of the social environment as a moderator of cardiovascular responding during psychological challenge. Models and evidence from related behavioral sciences (Psychometric Theory and Social Psychology, respectively) have provided useful guidance for this work. Relevant background and current data examining the measurement and determinants of cardiovascular reactivity are reviewed, with a focus on these multidisciplinary contributions. The implications of the work for the construct of reactivity and its possible role as a marker of disease risk are discussed.


The identification of concealed memories using the event-related potential and implicit behavioral measures: a methodology for prediction in the face of individual differences. The development and validation of an event-related potential (ERP) memory assessment procedure is detailed. The procedure identifies learned material with high rates of accuracy, whether or not subjects give intentional responses indicating they had previously learned it. Because the traditional analysis of variance approach fails to provide probabilistic conclusions about any given individual, Bayesian posterior probabilities were computed, indicating the probability for each and every person that material was learned. The method was developed on a sample of 20 subjects, and then cross-validated on two additional samples of 20 subjects each. Across the three samples, the method correctly defined over 94% of learned material as learned, and misclassified 4% of the unlearned material. Additionally, in a simple oddball task performed by the same subjects, the method classified rare and frequent material with perfect accuracy. Finally, combining two implicit behavioral measures--mean reaction time and the number of incorrect responses--in Bayesian fashion yielded classification accuracy that actually exceeded that of the ERP-based procedure overall, but the two methods provided identical accuracy in classifying the most critical material as recognized.


Event-related potentials and autonomic responses to a change in unattended auditory stimuli. Event-related brain potentials (ERPs) and autonomic nervous system (ANS) responses to occasional pitch and rise-time changes in a task-irrelevant auditory stimulus repeating at short intervals were measured while the subject performed a difficult intellectual task (Raven Matrices). It was found that deviant stimuli elicited the mismatch negativity (MMN) component of the ERP even when they elicited no ANS response. There was no significant difference in the mismatch negativity between trials in which the skin conductance response was or was not elicited. The pitch deviant tone also elicited heart rate deceleration, whereas the rise-time deviant tone tended to elicit a later heart rate acceleration. Neither heart rate change correlated with the mismatch negativity. The pattern of results obtained suggests that the mismatch negativity is generated by an automatic discrimination process associated with the cerebral events initiating the orienting response to stimulus change, but does not necessarily lead to the orienting response elicitation. Longer-latency ERP components tended to show slight covariation with ANS responses. The P3 was larger when a skin conductance response was elicited than when it was not elicited. Further, heart rate change trials tended to be accompanied by larger slow waves than trials with no heart rate response. Heart rate acceleration trials were accompanied by a larger slow parietal positivity and a smaller frontal negativity than were heart rate deceleration trials.


The temporal locations of heartbeat sensations. This experiment examined individual differences in the temporal location of heartbeat sensations and the reliability of their detection. Following practice on a familiarization task in judging light-tone simultaneity, 50 subjects were studied for two sessions on a heartbeat detection task, which required judging the simultaneity of heartbeat sensations and tones presented at six intervals following the onset of ventricular contraction. Subjects inspected the heartbeat-tone intervals as frequently and for as long as desired before choosing the one in which heartbeat sensations and tones were most simultaneous. The temporal locations of heartbeat sensations in subjects classified as "good heartbeat perceivers" (n = 16) ranged from 131 and 363 ms following ventricular contraction (mean = 228 ms). Correlations between the familiarization and heartbeat detection tasks in the accuracy of simultaneity judgments and in the frequency and duration of interval inspections suggest that general perceptual abilities and strategies may underlie success in detecting heartbeat sensations.


Mismatch negativity in event-related potentials to auditory stimuli as a function of varying interstimulus interval. The mismatch negativity, isolated as a component of the event-related brain potential elicited by deviant auditory stimuli, was suggested by Näätänen (1984) as an indirect measure of the inferred neuronal representation of standard stimuli. The purpose of the present study was to determine the duration of the neuronal representation by varying the interstimulus intervals of 1, 6, and 10 seconds within experimental blocks. Mismatch negativities were found to be elicited by deviant stimuli (1500-Hz tones, sequential probability 10%) following standard stimuli (1000-Hz tones) with interstimulus intervals of 1, 6, and 10 s as well. The results suggest a duration of neuronal representation of at least 10 s. The within-block variation of interstimulus interval, the rather low temporal probability of deviants, and their large frequency deviance might explain the present results contradicting earlier findings that suggested a shorter duration of that neuronal representation.


Ambulatory monitoring of respiration: inhibitory breathing in the natural environment. Because previous work found that sustained inhibitory breathing (i.e., low frequency breathing without increased tidal volume) can occur in laboratory animals under conditions of behavioral stress, this study sought to determine whether a comparable respiratory pattern could be observed in ambulatory human subjects in their natural environments. Tidal volume, breathing frequency, and minute ventilation were monitored continuously during 24-hour sessions via inductive plethysmography and a portable microprocessor. Mean tidal volume and minute ventilation were significantly higher during the daytime than at night for all subjects. However, mean breathing frequency was not consistently higher during the daytime, because episodes of low frequency breathing offset episodes of high breathing frequency. Tidal volume during low frequency breathing was comparable to that observed during medium or high frequency breathing. Thus, low frequency breathing was indicative of low minute ventilation. The eliciting stimuli, physiological concomitants, and relevance to health of this energetically inefficient breathing pattern remain to be determined.


Family history of hypertension and cardiovascular changes during high and low affect provocation. The present study investigated whether subjects with a positive family history of hypertension would display differential responses in blood pressure and heart rate across different laboratory tasks. We also wanted to know whether subjects would display stable within-subject responses across different laboratory tasks. Twenty-three family history positive subjects and 23 with a negative family history participated in three tasks: 1) mental arithmetic, 2) a conversation about the weather (low affect task), and 3) a conversation about a recent upsetting, interpersonal event (high affect task). Positive family history was associated with elevated diastolic resting blood pressure and greater diastolic responsivity overall. For both groups, arithmetic was associated with the greatest heart rate changes, whereas the distressing conversation was accompanied by the greatest diastolic blood pressure response. Stability of cardiovascular activation across different tasks was present only for heart rate; it was weak for diastolic blood pressure, and completely absent for systolic blood pressure.


The 24-hour sleep propensity function: experimental bases for somnotypology. The present study investigated the temporal structure of sleep propensity during 48 hours using an ultrashort 7-min sleep/13-min wake cycle. Eight subjects were tested under two experimental conditions of either attempting sleep, or resisting sleep after a monitored night in the laboratory. Electrophysiological recordings were carried out during the 7-min trials. The temporal structure and the overall level of sleepiness of the 48-hour sleep propensity functions calculated from the amount of total sleep in each trial revealed a high within-subjects stability. This was found both across the two days of the study within conditions, and across conditions. Also, diurnal levels of sleepiness were systematically related to nocturnal sleep parameters. Subjects having short nocturnal sleep latencies and higher sleep efficiencies slept more during the day. It is proposed that the structure and level of the sleep propensity function can be used to characterize individuals along two dimensions of somnotypology: "morningness-eveningness" and "sleepy-alert."


Psychometric properties of resting anterior EEG asymmetry: temporal stability and internal consistency. We examined whether resting anterior electroencephalographic (EEG) asymmetry in the alpha frequency band has psychometric properties that would be expected of a measure assessing individual differences. In each of two experimental sessions, separated by three weeks, resting EEG in midfrontal and anterior temporal sites was recorded from 85 female adults during eight 60-s baselines. Resting alpha asymmetry demonstrated acceptable test-retest stability and excellent internal consistency reliability. Analyses including other frequency bands indicated that degree of stability varied somewhat as a function of band and region. In addition, asymmetry was less stable than absolute power. Discussion focuses on the implications of the present findings for the measurement and conceptualization of resting anterior asymmetry.


A developmental event-related potential study of picture matching in children, adolescents, and young adults: a replication and extension. Event-related potentials were recorded in a developmental study of picture matching using an adaptation of Posner's (1978) letter-matching tasks. Subjects ranging in age from 6-39 were asked to decide whether two line drawings, presented sequentially, were the same or different on the basis of physical (physical identity), nominal (name identity), or categorical (category identity) criteria. The amplitude of a negativity at 400 ms (Neg400) increased as the number of dimensions on which the two line drawings differed increased. This effect held for all age groups, and was interpreted as reflecting the degree of semantic and/or physical relationship between the two pictures. However, one finding for Neg400 did suggest a qualitative difference in processing mode between the younger and older subjects. Both Neg400 and P3b latencies showed highly significant linear age trends, decreasing with increasing age. These age-related changes were interpreted as demonstrating quantitative speed of processing differences among age groups. The latencies of both Neg400 and P3b increased as the matching criteria became more complex. Moreover, P3b latency increased as the number of dimensions on which the two pictures differed increased, and this did not interact with age. Although both Neg400 and P3b showed age-related changes in scalp distribution, the fact that each was related to the experimental variables in similar fashion in all age groups suggested that they were homologous components across the age range studied. Taken as a whole, the data support continuity of information processing during these tasks across a wide age range.


Posttraumatic stress symptoms in victims of childhood incest. The relationship between posttraumatic stress disorder (PTSD) and the experience of severe childhood incest was investigated in a comparison of 97 adult female victims of incest and 65 matched controls. It appeared that 62% of the incest victims and none of the controls met the DSM-III-R criteria for PTSD. The best predictor for the development of PTSD appeared to be the subjective reaction at the time of the event, consisting of anxiety, freezing and dissociation. The incest victims also displayed other psychiatric symptoms, such as self-mutilation and conversions. Although the relation incest-PTSD is quite obvious, the diagnosis may easily be missed because the symptoms may be masked by other psychiatric phenomena.


Father kills mother: post-traumatic stress disorder in the children. Results of a study of over 100 children whose father killed their mother have been summarized and principles for practice have been formulated. All children orphaned by the death of one parent at the other's hands should be seen as soon as possible in a child psychiatry department and assessed. An immediate crisis intervention will probably be needed if they witnessed the killing to prevent PTSD. Bereavement counselling will be helpful in most cases. The caretakers will need support and help with their own mourning. Placement, access and custody, compensation, seeing the body, attending the funeral and dealing with family conflict will all need consideration. Long-term follow-up and further research are recommended.


Fluvoxamine treatment for chronic PTSD: a pilot study. A group of 24 Dutch World War II Resistance veterans with a documented traumatic war history and a (partially) positive diagnosis of current posttraumatic stress disorder (PTSD) was studied. This special group of war victims is characterised by chronicity, suffering from intractable posttraumatic complaints for decades. They were treated with fluvoxamine (Fevarin), a selective serotonin reuptake inhibitor with antidepressive and anxiolytic properties. The study was designed as an open-ended, outpatient pilot study, with a treatment period of 12 weeks. Results of clinical examination, and questionnaires investigating PTSD, depression, sleeping problems, anxiety, and vital exhaustion indicate that a significant number of the subjects improved with respect to their PTSD symptomatology, and their symptoms of anxiety and vital exhaustion. However, at the end of the study, quantitative improvement was modest. The results indicate that treatment with fluvoxamine may offer alleviation of chronic PTSD symptoms, in particular insomnia, nightmares, anxiety, intrusive recollections, guilt feelings and tiredness.


Current posttraumatic stress disorder and cardiovascular disease risk factors in Dutch Resistance veterans from World War II. The extraordinary trauma experienced by Resistance veterans from World War II (WW II) and other veterans may be associated with an increased incidence of posttraumatic stress disorder (PTSD) and somatic morbidity, including cardiovascular disease (CVD). This study explored some relationships between current PTSD and CVD risk factors in 147 male Dutch WW II Resistance veterans. They were compared to 65 same-aged male patients with a recent myocardial infarction and 79 surgical patients. Of these subjects, WW II Resistance veterans scored highest on CVD risk factors (i.e., angina pectoris, type A behavior, life stressors, and vital exhaustion), except smoking. Fifty-six percent of these veterans were currently suffering from PTSD. They reported CVD risk factors, in particular type A behavior and vital exhaustion, more often than veterans without PTSD; they also reported more premorbid adverse living conditions. These data suggest that early sensitization to environmental stressors may be associated with a high prevalence of current PTSD and excess CVD risk factors in subjects exposed to extraordinary war-time trauma and that this may lead to vital exhaustion.


Anxiety, depression and anger in Dutch Resistance veterans from World War II. In this study, 147 Dutch Resistance veterans from WW II are evaluated on psychometric instruments for anxiety, depression and anger. Resistance veterans appeared to be more anxious, depressive and angry on these instruments compared to controls from the validation studies of the respective instruments. Veterans currently suffering from PTSD (56%) were significantly more anxious, depressed, and angry than veterans without PTSD. With respect to staying in Nazi concentration camps, which is an extremely severe stressor, and in which half of the veterans were imprisoned, no difference on the three instruments was found. Anxiety, depression and anger were observed to be highly interrelated in PTSD. The close interrelationship between anxiety and depression, anxiety and danger, and depression and anger mediated by way of anxiety is, however, not unique for traumatized subjects. It is argued that for Resistance veterans only the intrusive reminiscences of the stressful events discriminate this constellation of symptoms from subjects with an anxious-depressive symptomatology.


Somatic reenactment in the treatment of posttraumatic stress disorder. Somatic reenactments, like other intrusive symptoms in post-traumatic stress disorder, such as flashbacks and nightmares, reproduce the mental content of traumatic events. Four cases are presented from survivors of military trauma and civilian catastrophes. The patients were part of larger research projects carried out by the University of Cincinnati Traumatic Stress Study Center. Understanding such symptoms as repetitions of the trauma itself proved useful therapeutically, especially in consolidating the working alliance.


Swedish UN soldiers in Cyprus, UNFICYP: their psychological and social situation. Two Swedish rifle batallions serving as UN soldiers in Cyprus (UNFICYP) have been investigated with respect to their demographic background and motives for application for UN service. The comparison of symptoms of stress in general, of posttraumatic stress disorder specifically, and some other variables of reaction with various studies of Swedish UN soldiers in different settings has given the following results. Very few interviewees experienced 'personal nervous breakdown' (0.5%). The soldiers reported in general very few psychological or psychosomatic complaints in the short time perspective. There seemed, however, to be two groups of persons at risk, namely those who were repatriated and those with a high consumption of alcohol.


Stereotypies in sows during chronic stress. In pig husbandry sows are fixed in such a way that they undergo a chronic loss of control over their environment. In these conditions sows develop stereotypies that are associated with a specific activation of brain endorphins. Stereotyping itself reduces some neuroendocrine stress symptoms. During stress at least two coping styles can be distinguished in many mammals and birds. These types are found again in the stressed sows which either maintain a high or a low level of stereotypies. The low stereotyping sows show the strongest signs of uneasiness.


Post-traumatic stress disorder in child survivors of shipping disasters: the sinking of the 'Jupiter'. 334 of over 400 children who survived the sinking of the cruise ship, Jupiter, in Athens harbour in October 1988 completed a battery of questionnaires 5-9 months later. Compared with age- and sex-matched controls, they show significantly higher scores on depression and anxiety. They also report more fears, particularly of stimuli related to the trauma. Overall, their scores on the Impact of Events Scale are as high as those reported by adults in other disasters. Follow-up studies a year after the accident reveal that nearly half the children meet the DSM-III-R criteria for PTSD. The usefulness of this screening battery is discussed. Some evidence for the effects of early intervention in schools is presented.


The role of psychological factors in gastrointestinal conditions. A review pertinent to DSM-IV. The authors reviewed the literature to assess the relationship between psychological factors and gastrointestinal conditions. The conditions that were found to be more relevant and worthy of future investigation were nonulcerative dyspepsia, inflammatory bowel disease (regional enteritis), and irritable bowel syndrome. The pertinent findings suggest that an important link exists between psychological factors and gastroenterological disorders, which supports the need for modification of the DSM-III-R's diagnostic category, "Psychological Factors Affecting Physical Condition." In concert with a subcommittee addressing other organ systems and psychological factors, the authors conclude that a diagnostic approach with greater utility would be useful for both researchers and clinicians. A conceptual framework as proposed in DSM-IV could also advance knowledge of psychological factors and their contribution or role in the etiology, perpetuation, and exacerbation of certain gastrointestinal conditions.


Ophthalmologic effects of psychotropic medications. This article reviews the effects of psychotropic medications on the eye. Although some of these effects have been known for years, they have been largely ignored by psychiatrists. The ophthalmologic effects of antidepressants, neuroleptics, benzodiazepines, carbamazepine, and lithium in therapeutic doses and overdose are reviewed and their implications discussed. Recommendations are made for appropriate monitoring, treatment, and ophthalmologic referral of patients on these medications.


Diagnosis and treatments of hypochondriacal syndromes. There are controversies in the literature about the diagnosis and most appropriate treatment of hypochondriasis. The author offers guidelines for diagnosis of hypochondriacal syndromes that have not been adequately dealt with in the literature and discusses the choice of treatments.


Detection of depression in the stroke patient. The literature suggests the hypothesis that nonpsychiatrists will underrecognize depression in evaluations of stroke patients. On a medical rehabilitation ward, 15 stroke patients were evaluated for depression by psychiatric interview and self-report. Charts were examined for detection of depression by the rehabilitation team. The hypothesis was supported: in contrast to psychiatric interview (68% depressed) and self-report (Beck Depression Inventory, 50% depressed), none of the patients were described as depressed in chart notes by the rehabilitation team (excluding the psychiatrists). Psychiatrists should develop ongoing interactions with primary care physicians to improve detection of poststroke depression and other depressions on medical wards.


Inpatient treatment of persistent somatization. Patients with disabling, persistent somatization pose significant challenges in clinical management. This study describes 92 patients treated on an inpatient psychosomatic medicine unit for persistent somatization. The most important factor in defining clinically significant subgroups of these patients was mood. Compared with depressed somatizing patients, nondepressed somatizing patients had chronic illnesses of early onset, had symptoms that were not correlated with current life stressors, and were generally unresponsive to treatment. There were few clinical predictors of treatment outcome apart from the duration of symptoms, the presence of mood disturbance, and a history of stable interpersonal relationships.


Panic disorder and chest pain in the coronary care unit. Consecutive admissions to a university hospital coronary intensive care unit were prospectively evaluated using a modified version of the Structured Clinical Interview for DSM-III-R by interviewers blind to the patient's cardiac status. Panic disorder was present in almost one-third of the patients. Four (21%) of the 19 patients with panic disorder also had positive cardiac findings, including 2 who had myocardial infarctions. Of the 27 patients with negative cardiac findings, 15 (55.5%) had panic disorder. Whereas panic disorder and coronary heart disease may coexist in patients with acute chest pain, there appears to be a very high prevalence of panic disorder among patients in whom cardiac disease has been excluded.


Trends in mortality from stroke in Scotland, 1950-1986. The Scottish Registrar General's Annual Reports have been used to study trends in mortality from stroke in Scotland during 1950-1986 in those aged 45 to 74. In 1950 the age-adjusted mortality rate was 347.4 per 100,000 population for men and 360.8 for women, falling to 199.6 for men and 155.8 for women in 1986. This downward trend has increased from 1976 for males. The average annual decline in age-adjusted mortality from stroke over the 37-year period was 4.0 per 100,000 in males and 5.5 in females. This reduction in death rates was proportionally higher for women compared with men in all age groups over 55 years. As with cardiovascular deaths, mortality from stroke was lower in the east than in the central region and west of Scotland. The reduction in mortality resulted in a substantial 'saving' of lives, estimated at 12,500 between 1980 and 1984.


General practitioners and public health. Family Health Service Authorities (FHSAs), since 1st April 1991, have been both 'managed', by the Regional Health Authority, and 'managing', their contractor services. Both situations are relatively new to them, their Region and the contractors. We examine the opportunities and potential problems of this major strategic change. These relate to: (1) the establishment of effective coordination between providers of primary care services; (2) the establishment of minimum basic standards of care and administration for GPs (based on those set for training practices by the Regional Advisors in General Practice); (3) the development and validation of a data collection system from General Practice which could be used to establish a morbidity database from general practice as a means of health needs assessment as well as for performance review.


Internal variation in the uptake of whooping cough immunisation within a Health Authority. Data were obtained on the vaccination history of 6,898 children immunised with D3, the final dose of diphtheria vaccine. These children were born between 1984 and 1990 and were also resident within a single Health Authority during part or all of this time. Analysis of this data revealed consistent variation by treatment centre in the uptake of whooping cough vaccine in those children receiving the diphtheria vaccine. Certain treatment centres consistently achieved greater success in giving the whooping cough vaccine to those children who had received the diphtheria vaccine.


Height, body mass index and mortality: do social factors explain the association? The aim of the study was to analyse the effects on mortality of body height and body mass index (BMI) in young men, taking into account social and behavioural characteristics in early youth. The study is a 20-year follow-up of all Swedish men (n = 50,465) conscripted for military service in 1969-70. Baseline data on body height and weight as well as interview and questionnaire data on social and behavioural characteristics were linked to mortality data up to the end of 1988. Nine hundred and forty-six men died during the follow-up. We found a significant increase in mortality by decreasing body height; persons below 165 cm had an almost twofold increased mortality compared with those of average height. This association was reduced to the limit of statistical significance when we controlled for social and behavioural characteristics in a multivariate model. Persons with a BMI above 30 had a more than twofold increased mortality compared with those of average BMI. This association remained highly significant in a multivariate model. We thus confirmed previous findings of an inverse association between body height and mortality, but found that this association was almost entirely due to social background factors. The independent association between BMI and mortality may indicate a stronger genetic influence on BMI than on body height.


Psychological ill-health in Chinese communities in Hong Kong. Psychiatric symptoms are widely distributed in the general population while psychiatric impairment or psychological ill-health is prevalent in many communities, especially those with stressful environments. Data concerning Chinese communities are scanty. The present study employed the use of a General Health Questionnaire to screen the general population for psychological ill-health in Hong Kong and the results showed that between 18.3% and 26.3% of Chinese could be considered as probable or potential candidates for mental illness. The authors discuss the significance of these findings.


Detection of subclinical ascorbate deficiency in early Parkinson's disease. From mid-October 1989 to mid-July 1990 all newly admitted residents to Bury Local Authority Residential Homes were comprehensively medically screened. In a series of 100 residents eight had early Parkinson's disease (six of them hitherto undiagnosed). Seven showed evidence of Vitamin C deficiency. Of the seven showing evidence of deficiency, four suffered from early Parkinson's disease. Of the 93 without evidence of Vitamin C deficiency only four had Parkinson's disease. This indicates a significantly higher prevalence of Parkinson's disease in the group with Vitamin C deficiency (P less than 0.001 using Fisher's exact).


Audit: what's in the name?

Audit: what's in the name? Medical audit is based on a cyclical model which is ideally suited to operational work that is (1) regularly repeated in similar situations; (2) clearly and directly linked to outcomes; (3) amenable to criteria of quality. The work of public health physicians is both operational (e.g. investigation of outbreaks of communicable disease) and strategic (e.g. health needs assessment). A cyclical model is not appropriate to strategic activity. Evaluation of that activity is essential--but should not be constrained/limited by inappropriate adherence to the audit cycle.


Towards a more rational policy for colposcopy. The objective of the study was to establish the relationship between the results of positive and abnormal cervical smears and the corresponding colposcopic biopsy results and its relevance to clinical management. A retrospective analysis of linked results was carried out at the Princess Anne Hospital, Southampton. The main outcome measure was the correspondence between a positive or abnormal cervical smear and the related colposcopic biopsy. Colposcopic biopsies were carried out on 1,841 consecutive women. Of these, 1,424 (77.4%) had moderate or severe dyskaryosis on their smears. Of the 1,767 with definitive results on their smear, 1,101 (62%) showed exact correspondence between the cervical smear and the colposcopic biopsy. Ninety-one (26%) of all women with mildly dyskaryotic smears were reported as showing CIN II or CIN III on biopsy. We conclude that women with moderate or severe changes on cervical smear should not be asked to attend for confirmatory colposcopic biopsy prior to treatment, but those with persistent mild changes should be referred for separate diagnostic colposcopy.


First year of AIDS services delivery under Title I of the Ryan White CARE Act. This is a review of (a) the emergency assistance for ambulatory HIV medical and support services provided in the first year by eligible metropolitan areas (EMAs) funded under Title I of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1990, (b) the varied responses and processes by which the 16 urban areas receiving Title I funds in 1991 met legislative mandates, (c) the central nature of planning councils under Title I and their formation and functioning, and (d) issues related to current implementation and future expansion of Title I to additional eligible metropolitan areas. Integral to the review is a brief discussion of the history of AIDS and HIV infection, particularly in cities receiving CARE Act funding, an overview of Title I requirements, and a description of the organizational structures cities are using to implement Title I. Information on Title I EMAs is based on analysis of their 1991 applications, bylaws of their HIV service planning councils, intergovernmental agreements between Title I cities and other political entities, and contracts executed by Title I grantees with providers for the delivery of services. Interviews with personnel in several Title I EMAs, including planning council members and grantee staff members, provided additional information. This is the first descriptive accounting of activities related to the 1991 applications for and uses of Title I funds, and the administrative and service issues related to this process.


15-month followup of women methadone patients taught skills to reduce heterosexual HIV transmission. Heterosexual contact with intravenous drug users accounts for a growing proportion of cases of acquired immunodeficiency syndrome (AIDS) among women. In an earlier study designed to reduce sexual risk behavior, the authors randomly assigned 91 methadone maintained women to information-only or skills-building conditions. Modest outcomes favored participants in the skills-building group. In this 15-month followup of 62 remaining study participants, skills-training group members were more likely than controls to use condoms. In comparison with controls, members in the skills-building group felt more comfortable talking about safe sex, perceived themselves as more able to reduce their exposure to AIDS, but were more likely to attribute AIDS risk to luck. No associations were found between group condition and number of sexual partners or frequency of buying and carrying condoms. Some gains associated with a group intervention tended to be maintained over time, indicating that preventive interventions composed of multiple sessions and conducted in treatment settings may have promise as useful strategies to prevent human immunodeficiency virus (HIV) infection. Nevertheless, decay was evident in other domains, suggesting that prevention specialists should consider booster sessions or other means of maintaining changes in risk behavior.


Sexual practices and AIDS knowledge among women partners of HIV-infected hemophiliacs. About 12 percent of the women sex partners of hemophilic men who are seropositive for the human immunodeficiency virus (HIV) have themselves become seropositive. Questionnaires were completed in January 1988 by 15 women who were in long-term, monogamous relationships with HIV-positive hemophiliacs; 11 of the women were not HIV seropositive and 4 were. None of the couples was abstaining from sexual intercourse, and during the 4 weeks prior to responding, the couples had intercourse a mean of 6.2 times. Sixty percent always used condoms, 13 percent did so most of the time, and the remaining 27 percent did sometimes. Condom use was not significantly related to either frequency of intercourse, the women's knowledge of acquired immunodeficiency syndrome (AIDS) and AIDS-risk reduction, the actual HIV status of both partners and the women's perceived status of both, the extent of the women's worry about contracting AIDS, their reported degree of negative impact from AIDS, or to their mood, age, or education. All women who reported not always using condoms had been informed of their own and their partner's HIV status; were counseled repeatedly regarding risk reduction; acknowledged the possibility of heterosexual HIV transmission; said they knew of recommendations for the use of condoms; recognized their risk of HIV infection; claimed some degree of worry about acquiring HIV through sexual activity; had children at home; and were not, with one exception, trying to become pregnant. There were several possible factors influencing the decision by women at high risk for acquiring HIV not to use condoms. Among them were complaints that the women found condoms unpleasant or an unwanted reminder of AIDS, a sense of obligation or a drive to continue unaltered sexual relations, the false reassurance of HIV-negative test results for some of the women who did not always use condoms, a willingness to sacrifice and to share their partner's fate, a desire to avoid communicating rejection and adding to their partner's burdens, and difficulty changing long-standing behavior patterns despite logical understanding of the risks involved.


One state's response to the malpractice insurance crisis: North Carolina's Rural Obstetrical Care Incentive Program. In the period 1985-89, there was a severe drop in obstetrical services in rural areas of North Carolina, partly because of rising malpractice insurance rates. The State government responded with the Rural Obstetrical Care Incentive (ROCI) Program that provides a malpractice insurance subsidy of up to $6,500 per participating physician per year. Enacted into law in 1988, the ROCI Program was expanded in 1991, making certified nurse midwives eligible to receive subsidies of up to $3,000 per year. To participate, practitioners must provide obstetrical care to all women, regardless of their ability to pay for services. Total funding for the program has increased from $240,000 to $840,000, in spite of extreme budgetary constraints faced by the State. The program and how its implementation has maintained or increased access to obstetrical care in participating counties are described on the basis of site visits to local health departments in participating counties and data from the North Carolina Division of Maternal and Child Health. The program is of significance to policy makers nationwide as both a response to rising malpractice insurance rates and reduced access to obstetrical care in rural areas, and as an innovative, nontraditional State program in which the locus of decision making is at the county level.


Measuring the quality of life of the elderly in health promotion intervention clinical trials. The Multicenter Trials of Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) is a series of clinical trials of biomedical, behavioral, and environmental interventions to reduce the risks of frailty and injury among the elderly. Reliable assessment of the quality of life reported by the subjects is a central issue in evaluating the interventions. An intervention may have a significant impact on an elderly person's sense of well-being, even though significant improvement is not observed in selected physical outcome measures. Elderly persons' compliance with particular intervention regimens may be influenced by the quality of life effects that they perceive in relation to the intervention. The researchers review the definition and measurement of quality of life in the trials, with particular attention to issues in determining common measures used at all study locations. Practical considerations in the selection and use of quality of life measures in both community and institutional populations are addressed. Topics discussed include the interrelation of aging, functional capacities, and quality of life; the multi-dimensionality of quality of life in relation to differential intervention effects; and age-related issues in the collection of quality of life data. Preliminary observations are reviewed, and potential contributions of FICSIT to intervention-sensitive quality of life assessments among the elderly are noted.