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Changes in motor responses induced by cerebellar stimulation during classical forelimb flexion conditioning in cat.

1. The ability of somaesthetic sensory inputs to produce structural changes in the connectivities of the central nervous structures involved in motor activity was tested with an alpha type of classical conditioning in chronically prepared adult cats. Repetitive sensory stimulation was applied at constant intervals after the activation of the motor circuits originating in the neurons or efferent axons of the cerebellar nuclei. A conditional stimulation (CS) applied to interpositus neurons was consistently paired with an unconditional stimulation (UCS) applied to the dorsal skin of the forelimb extremity to induce associative sensorimotor conditioning. The sites at which the conditional and unconditional stimuli were applied set up a simplified sensorimotor circuit including pathways transmitting both these stimuli and others mediating the expression of the conditioned responses. 2. To test the changes resulting from the conditioning, electrodes were implanted into the various relay structures on the cerebellar efferent pathways (ventrolateral nucleus motor cortex). The forelimb motor responses elicited by stimulating these relay structures were recorded with a potentiometer placed at the elbow joint. The angular displacement (amplitude) and latency of the responses and the percentage response rates were systematically quantified throughout the conditioning procedure and at test sessions carried out after the daily conditioning routines. 3. It was observed that daily repetition of paired CS-UCS led to an increase in the response rates and amplitudes of the forelimb flexions, which already began to occur very slightly on the first 4 or 5 days in response to the alpha conditioning, whereas the CS when applied alone failed to produce any changes in this initial response. Likewise, after the acquisition phase, repeated presentation of either the CS alone or the CS preceded by the UCS led to the extinction of the conditioned response, thus indicating that the observed changes were of an associative nature and that they depended on interactions between the motor and sensory inputs occurring somewhere in the CNS. In fact, the effects of conditioning were not generalized, but involved only a circumscribed circuit originating in the cerebellar neurons stimulated by the CS, which were activated concomitantly with the sensory pathways. 4. The conditioned response amplitudes were enhanced by 2.5-3 times their initial value. This enhancement persisted at the end of acquisition or after several days of consolidation, even when the paired CS-UCS sessions were interrupted for a period of 15 days to 2 mo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Single olivocochlear neurons in the guinea pig. II. Response plasticity due to noise conditioning.

Previous studies have shown that daily, moderate-level sound exposure, or conditioning, can reduce injury from a subsequent high-level noise exposure. We tested the hypothesis that this conditioning produces an increased activity in the olivocochlear efferent reflex, a reflex known to provide protection to the cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2-4 kHz noise at 85 dB sound pressure level. This conditioning is known to reduce damage from a subsequent high-level exposure to the same noise band. Responses to monaural and binaural sound were recorded from single medial olivocochlear (MOC) efferent neurons, and data from conditioned animals were compared with those obtained from unexposed controls. MOC neurons were classified by their response to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra units, or either-ear units. There were no significant differences in the distributions of these unit types between control and conditioned animals. There were also no differences in other responses to monaural stimuli, including the distribution of characteristic frequencies (CFs), the sharpness of tuning, or thresholds at the CF. For binaural sound at high levels, particularly relevant to sound-evoked activation of the MOC reflex during acoustic overstimulation, the firing rates of MOC neurons with CFs just above the conditioning band showed slight (but statistically significant) elevations relative to control animals. Frequency regions just above the conditioning band also demonstrated maximum conditioning-related protection; thus protection could be due, in part, to long-term changes in MOC discharge rates. For binaural sound at low levels, MOC firing rates in conditioned animals also were increased significantly relative to controls. Again, increases were largest for neurons with CFs just above the conditioning band. For equivalent monaural sound, rates were not significantly increased; thus, conditioning appears to increase binaural facilitation by opposite-ear sound. These data indicate that MOC neurons show long-term plasticity in acoustic responsiveness that is dependent on their acoustic history.

Acoustic Stimulation↗

Effects of hippocampal lesions on conditional discriminations in rats.

Effects of hippocampal lesions on conditional discrimination were examined in rats. Rats were trained in a conditional drug discrimination paradigm using pentobarbital. They were able to learn the discrimination. After hippocampal lesions, all rats maintained discrimination. Thus a hippocampal lesion had no effect on retention of the conditional discrimination with drugs. Another group was trained in the same conditional discrimination except that the conditional stimuli were two different flashing lights. Similarly to the drug discrimination, only one of the two light conditioning stimuli was presented in one training session. No rat was able to learn the discrimination. New rats were trained in conventional conditional discrimination, in which the two conditional stimuli (flashing lights) were repeatedly presented within one training session. Hippocampal lesions made after learning this discrimination had no effect on retention. The present study reveals that the hippocampus does not have a crucial role in conditional discrimination learning when conditional stimuli were drugs and that rats could not learn conditional discrimination when two external conditional stimuli were presented in a similar way to the internal stimuli (drug discrimination paradigm).

Animals↗

Trace conditioning and the hippocampus: the importance of contiguity.

Trace conditioning, a form of classical conditioning in which the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) is separated in time by an interstimulus interval, requires an intact hippocampus. In contrast, classical conditioning procedures in which the CS and US are not separated by an interstimulus interval (i.e., delay conditioning procedures) typically do not (Solomon et al., 1986). However, why trace conditioning is dependent on the hippocampus is unknown. Several theories suggest that it is specifically the discontiguity between the CS and US in trace conditioning that critically engages the hippocampus. However, there are other explanations that do not depend on discontiguity. To determine whether the lack of contiguity renders trace conditioning hippocampal dependent, we designed a "contiguous trace conditioning" (CTC) paradigm in which CS-US contiguity is restored by re-presenting the CS simultaneously with the US. Although rats with excitotoxic lesions of the hippocampus could not learn a standard trace fear-conditioning paradigm, lesioned rats trained on CTC showed significant conditioning, at levels similar to those with sham surgeries. Importantly, lesioned rats trained solely with simultaneous CS-US presentations did not demonstrate conditioning. Together, these data suggest that rats with hippocampal lesions can form a memory of a trace CS-US association when contiguity is restored. Therefore, the dependence of traditional trace paradigms on the hippocampus can be attributed to the absence of temporal contiguity.

Animals↗

Differential effects of cerebellar inactivation on eyeblink conditioned excitation and inhibition.

The neural mechanisms underlying excitatory and inhibitory eyeblink conditioning were compared using muscimol inactivation of the cerebellum. In experiment 1, rats were given saline or muscimol infusions into the anterior interpositus nucleus ipsilateral to the conditioned eye before each of four daily excitatory conditioning sessions. Postinfusion testing continued for four more excitatory conditioning sessions. All rats were given a final test session after muscimol infusions. The muscimol infusions inactivated the cerebellar nuclei, lateral anterior lobe, crus I, rostral crus II, and lobule HVI ipsilateral to the conditioned eye. Acquisition of excitatory conditioning was completely prevented by muscimol inactivation. In experiment 2, there were four experimental phases. Phase 1 consisted of excitatory conditioning. In phase 2, rats were given saline or muscimol infusions before conditioned inhibition training. Phase 3 consisted of continued conditioned inhibition training with no drug infusions. In phase 4, all rats received a retardation test in which the inhibitory stimulus was paired with the unconditioned stimulus. Muscimol infusions blocked the expression of conditioned responses during phase 2. However, robust conditioned inhibition was evident in phases 3 and 4. The findings indicate that conditioned excitation and inhibition depend on different mechanisms.

Animals↗

Choice with uncertain outcomes: conditioned reinforcement effects.

Pigeons responded on concurrent chains with equal initial- and terminal-link durations. In all conditions, the terminal links of one chain ended reliably in reinforcement; the terminal links on the alternative chain ended in either food or blackout. In Experiment 1, the terminal-link stimuli were correlated with (signaled) the outcome, and the durations of the initial and terminal links were varied across conditions. Preference did not vary systematically across conditions. In Experiment 2, terminal-link durations were varied under different stimulus conditions. The initial links were variable-interval 80-s schedules. Preference for the reliable alternative was generally higher in unsignaled than in signaled conditions. Preference increased with terminal-link durations only in the unsignaled conditions. There were no consistent differences between conditions with and without a common signal for reinforcement on the two chains. In the first series of conditions in Experiment 3, a single response was required in the initial links, and the stimulus conditions during 50-s terminal links were varied. Preference for the reliable outcome approached 1.0 in unsignaled conditions and was considerably lower (below .50 for 3 of 5 subjects) in signaled conditions. In a final series of signaled conditions with relatively long terminal links, preference varied with duration of the initial links. The results extend previous findings and are discussed in terms of the delay reduction signaled by terminal-link stimuli.

Animals↗

Sign- versus goal-tracking: effects of conditioned-stimulus-to-unconditioned-stimulus distance.

Three pigeons were exposed sequentially across experimental phases to five different distances between the conditioned stimulus and the site of the unconditioned stimulus in a sign-/goal-tracking procedure. A computer-controlled tracking system provided a continuous record of the bird's position by continuously monitoring the location of the bird's head in three-dimensional space. It was found that birds sign-tracked (i.e., approached the conditioned stimulus) when the conditioned stimulus was closest to the site of the unconditioned stimulus, goal-tracked (i.e., approached the site of the unconditioned stimulus in the presence of the conditioned stimulus) when the conditioned stimulus was farthest from the site of the unconditioned stimulus, and engaged in both sign- and goal-tracking (or something intermediate) at intermediate conditioned-stimulus-to-unconditioned-stimulus distances. When both sign- and goal-tracking occurred, the former tended to occur in the first half and the latter in the second half of the interval in which the conditioned stimulus was present. The results suggest (a) whether sign- or goal-tracking (or both) occurs is a function of the distance of the conditioned stimulus from the site of the unconditioned stimulus, (b) the fact that pigeons but not rats have been found to sign-track consistently throughout the duration of the conditioned stimulus may be due to quantitatively rather than qualitatively different effects of conditioned-stimulus-to-unconditioned-stimulus distance across species (i.e., a "short" conditioned-stimulus-to-unconditioned-stimulus distance for a pigeon may be a "long" one for a rat), and (c) sign- and goal-tracking may be competing behavioral tendencies that can (e.g., at intermediate conditioned-stimulus-to-unconditioned-stimulus distances) cancel each other out. The findings lend support to theories that specify an interaction between phylogenetic and reinforcement variables in determining whether sign- or goal-tracking will occur in any given experimental preparation.

Animals↗

High intensity exercise conditioning increases accumulated oxygen deficit of horses.

High intensity exercise is associated with production of energy by both aerobic and anaerobic metabolism. Conditioning by repeated exercise increases the maximal rate of aerobic metabolism, aerobic capacity, of horses, but whether the maximal amount of energy provided by anaerobic metabolism, anaerobic capacity, can be increased by conditioning of horses is unknown. We, therefore, examined the effects of 10 weeks of regular (4-5 days/week) high intensity (92+/-3 % VO2max) exercise on accumulated oxygen deficit of 8 Standardbred horses that had been confined to box stalls for 12 weeks. Exercise conditioning resulted in increases of 17% in VO2max (P<0.001), 11% in the speed at which VO2max was achieved (P = 0.019) and 9% in the speed at 115% of VO2max (P = 0.003). During a high speed exercise test at 115% VO2max, sprint duration was 25% longer (P = 0.047), oxygen demand was 36% greater (P<0.001), oxygen consumption was 38% greater (P<0.001) and accumulated oxygen deficit was 27% higher (P = 0.040) than values before conditioning. VLa4 was 33% higher (P<0.05) after conditioning. There was no effect of conditioning on blood lactate concentration at the speed producing VO2max or at the end of the high speed exercise test. The rate of increase in muscle lactate concentration was greater (P = 0.006) in horses before conditioning. Muscle glycogen concentrations before exercise were 17% higher (P<0.05) after conditioning. Exercise resulted in nearly identical (P = 0.938) reductions in muscle glycogen concentrations before and after conditioning. There was no detectable effect of conditioning on muscle buffering capacity. These results are consistent with a conditioning-induced increase in both aerobic and anaerobic capacity of horses demonstrating that anaerobic capacity of horses can be increased by an appropriate conditioning programme that includes regular, high intensity exercise. Furthermore, increases in anaerobic capacity are not reflected in blood lactate concentrations measured during intense, exhaustive exercise or during recovery from such exercise.

Aerobiosis↗

Neurotoxic basolateral amygdala lesions impair learning and memory but not the performance of conditional fear in rats.

We examined the influence of extensive overtraining (75 trials) on the impact of neurotoxic basolateral amygdala (BLA) lesions on Pavlovian fear conditioning in rats. As we have shown previously, pretraining BLA lesions yielded severe deficits in the acquisition of conditional freezing in rats trained with either 1 or 25 conditioning trials. However, extensive overtraining (50 or 75 trials) mitigated deficits in conditional freezing. Under these conditions the rats with BLA lesions expressed normal and robust freezing behavior, although they required at least 10 times as much training as control rats to reach this level of performance. The ability of rats with BLA lesions to acquire and express conditional freezing after extensive overtraining was modality-specific; conditional freezing in individual rats was acquired to contextual, but not acoustic, conditional stimuli. These results suggest that neural circuitry outside of the amygdala can mediate contextual fear conditioning under some conditions. In contrast to pretraining lesions, post-training BLA lesions eradicated the memory for Pavlovian fear in rats trained with either 1 or 75 trials; this deficit was not modality-specific. Together, these results reveal that impairments in the acquisition and expression of conditional fear in rats with BLA lesions are not attributable to deficits in the performance of the freezing response but are attributable to disruptions in the learning and memory of Pavlovian fear conditioning.

Acoustic Stimulation↗

Nursing experiences with an alcohol-intoxicated rat dam counteract appetitive conditioned responses toward alcohol.

BACKGROUND: Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol. METHODS: Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13. RESULTS: Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning. CONCLUSIONS: The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content.

Alcoholic Intoxication↗

Conditioning as a critical determinant of sensitization induced by psychomotor stimulants.

It is apparent that stimuli associated with psychomotor stimulants as well as opiates acquire the ability to elicit motor behaviors that probably reflect the acquisition and operation of incentive motivational processes. Such conditioning also appears to be a critical determinant of behavioral sensitization seen with repetitive administration of these agents. The conditioning of motor excitation to stimuli associated with psychomotor stimulants follows the principles of classical conditioning and is relatively long lasting. Dopaminergic mechanisms appear to be involved in the acquisition of such conditioned behaviors, since neuroleptics are effective blockers of the process. Dopaminergic blockade probably disrupts conditioning through several different mechanisms including attenuation of the conditioned and unconditioned excitatory properties of the CS and blockade of the US. DA blockade prevents stimuli associated with psychomotor stimulants from acquiring and subsequently generating positive affective motivational states that are reflected by increases in motoric output. While dopamine appears to be necessary for the formation of conditioned motor excitation, it is not critically involved in the expression of the conditioned effects. This seems to suggest that DA may serve only to modulate the formation of motivationally significant associations but is not involved in the expression of conditioned drug effects that may be mediated through DA-independent pathways. The amygdala and nucleus accumbens are two structures in the CNS involved in the acquisition of conditioned motor excitation. Interestingly, both of these brain regions are the recipients of mesolimbic DA input. Dopamine probably plays different roles in each region during the conditioning process. In the amygdala, mesolimbic DA may serve to modulate processes that attach emotional significance to environmental stimuli; further, DA may play a role in determining which stimuli gain access to structures afferent to the amygdala, including the nucleus accumbens. Dopamine in the nucleus accumbens, on the other hand, serves to determine which limbic inputs gain access to the motor pathways. In this way, DA in the nucleus accumbens may translate the motivational determinants of behavior that are mediated by limbic structures into biologically relevant actions. Understanding the mechanisms that determine the conditioning of drug effects to associated stimuli also has possible relevance for elucidating processes underlying addictive behaviors. For example, it has been proposed (Stewart et al. 1984) that the acquisition of incentive motivational properties by stimuli associated with drugs determines the craving in addicts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of N6-(L-phenylisopropyl)adenosine, caffeine, theophylline and rolipram on the acquisition of conditioned responses in the rabbit.

This study examined the effects of caffeine, theophylline and rolipram on the acquisition of conditioned responses in the rabbit and their ability to antagonize the retardant effects of the adenosine analog N6-(L-phenylisopropyl)adenosine (L-PIA) on acquisition. Pavlovian conditioning of nictitating membrane extension was accomplished by pairing the offset of a 800-msec tone- and light-conditioned stimulus with the onset of a 100-msec shock unconditioned stimulus to the skin just lateral to the outer canthus of the eye. L-PIA (5 mumol/kg) retarded the acquisition of conditioned responses to the tone- and light-conditioned stimuli, although theophylline (50-200 mumol/kg), caffeine (3-100 mumol/kg) and rolipram (0.03-3.0 mumol/kg) had no effect. The highest dose of caffeine used (300 mumol/kg) produced a small but significant enhancement of conditioned response acquisition in two of four experiments. The two adenosine antagonists theophylline (200 mumol/kg) and caffeine (300 mumol/kg) completely blocked the retardant effects of L-PIA on acquisition, although the phosphodiesterase inhibitor rolipram (3.0 mumol/kg) did not. In previously trained animals, L-PIA (5 mumol/kg) also increased the intensity threshold of a tone-conditioned stimulus for eliciting conditioned responses by more than 10 db. Theophylline (200 mumol/kg) and caffeine (300 mumol/kg) had no effect on the intensity threshold of the tone-conditioned stimulus but completely antagonized the effects of L-PIA. It was suggested that the depressant effects of the adenosine analog L-PIA on both the acquisition of conditioned responses and on the ability of a conditioned stimulus to elicit conditioned responses as soon as learning had occurred were mediated by adenosine receptors.

Adenosine↗

Context and Pavlovian conditioning.

Procedurally, learning has to occur in a context. Several lines of evidence suggest that contextual stimuli actively affect learning and expression of the conditional response. The experimental context can become associated with the unconditional stimulus (US), especially when the US is presented in a context in the absence of a discrete conditional stimulus (CS). Moreover, context can modulate CS-US associations. Finally, it appears that context can become associated with the CS when it is presented before the CS-US training. The purpose of the present paper is to review some of the relevant literature that considers the context as an important feature of Pavlovian conditioning and to discuss some of the main learning theories that incorporate the context into their theoretical framework. The paper starts by mentioning historical positions that considered context an important variable in conditioning and then describes how the approach to contextual conditioning changed with the modern study of Pavlovian conditioning. Various forms of measurement of context conditioning are presented and the associative strength attached to context in several experimental paradigms is examined. The possible functions that context may acquire during conditioning are pointed out and related to major learning theories. Moreover, the effect of certain neurological manipulations on context conditioning is presented and these results are discussed in terms of possible functions that the context might acquire during Pavlovian conditioning. It is concluded that contextual stimuli acquire different functions during normal conditioning. A procedure in which animals are exposed to an aversive US immediately after they are placed in the experimental context is suggested as a useful control for the study of context conditioning.

Animals↗

Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus.

We investigated the importance of endogenous amino acids in the locus coeruleus in inescapable electric shock and conditioned fear. In naive rats and in rats exposed to noise (N), light (L) and electric shock (S) or to N + L only, the locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of GABA, taurine, glutamate, aspartate, serine and glutamine was determined in the superfusate by HPLC after derivatization with o-phthaldialdehyde. Locomotor activity, arterial blood pressure and heart rate were telemetrically monitored. The placement of naive rats or conditioned rats from their home cage to a chamber provided with a grid-floor for shock virtually did not change the release rates of the amino acids in the locus coeruleus. Motility was enhanced in naive and conditioned rats to a similar extent. Blood pressure and heart rate were enhanced in conditioned rats only. Exposure to N + L + S for 5 min greatly enhanced the release rates of all determined amino acids in the locus coeruleus. In conditioned rats the increase in release of most amino acids lasted longer than in naive rats. Electric shock also enhanced motility, blood pressure and heart rate. In conditioned rats, motility and cardiovascular changes were more pronounced and/or lasted longer than in naive rats. Exposure of conditioned rats to the conditioned stimuli N + L for 5 min led to an increased release of taurine and aspartate. The enhanced release of taurine lasted 30 min. Exposure to N + L did not affect the release rates of amino acids in naive rats. N + L did not influence motility but arterial blood pressure and heart rate were elevated in conditioned rats. The findings show that inescapable electric shock enhances the release of several amino acids in the locus coeruleus, while conditioned fear selectively increases the outflow of taurine and aspartate. Moreover, conditioned fear prolongs the response of excitatory and inhibitory amino acids to electric shock. The results suggest that an excitatory amino acid (aspartate) and an inhibitory amino acid (taurine) of the locus coeruleus are implicated in conditioned fear.

Amino Acids↗

Morphological and functional preservation of the outer hair cells from noise trauma by sound conditioning.

Guinea pigs were sound conditioned to a low-level, long-term pure tone stimulus (1 kHz, 81 dB SPL, 24 days) before exposure to a traumatic noise (1 kHz, 105 dB SPL, 72 h). Auditory brainstem response thresholds and distortion product otoacoustic emissions were obtained at selected frequencies before sound conditioning and at day 1, 5, 10, and 15 during sound conditioning as well as on the final 24th day. Auditory brainstem responses at 1 and 2 kHz were not affected at any time during sound conditioning. The amplitude of the distortion product otoacoustic emission showed minor alterations (below 10 dB) at selected frequencies only during the initial stages (day 1, 5, and 10) of sound conditioning in some, but not all the animals. Distortion product amplitudes were similar to control values on the 15th and 24th day of conditioning. Surface preparations of the organ of Corti did not reveal any significant hair cell loss induced by sound conditioning. The effect of a traumatic exposure (1 kHz, 105 dB SPL, 72 h) on a control group and a sound conditioned group was determined. The distortion product otoacoustic emission amplitude measured 4 weeks after the cessation of the traumatic exposure revealed significant differences. The amplitude of the distortion product otoacoustic emission for the control group was depressed at all tested frequencies and at lower frequencies (2.8, 2.1, and 1.75 kHz) the emissions did not show an increase in response to increases in intensity, of the primaries. The sound conditioned group showed increases in distortion product amplitude with increases in the intensity of the primaries for all tested frequencies and statistically significant reductions from the pre-exposure values were not found. Surface preparations from the control group indicated that the traumatic noise exposure affected nearly 100% of the outer hair cells around the 14 mm distance from the round window. The sound conditioned group showed a significantly less (50%) outer hair cell loss than the control group. The sound conditioned group illustrated an altered pattern of damage after subsequent noise trauma. There were two distinct regions of outer hair cell loss, one being around the 16 mm distance and the other around the 12 mm distance from the round window. These results imply that the intrinsic properties of the outer hair cells and/or the organ of Corti have been altered by sound conditioning.

Acoustic Stimulation↗

Emotional well-being among adolescents with and without chronic conditions.

PURPOSE: To investigate whether adolescents with chronic conditions differ from adolescents without chronic conditions in several psychological outcomes. An additional purpose was to explore whether adolescents with chronic conditions differ as a function of the visibility of their conditions. METHODS: By means of the Adolescent Health Survey, 1683 students (grades 7-12) with a variety of chronic conditions were compared with 1650 students without chronic conditions in regard to emotional well-being, worries and concerns, and body image. Differences in emotional well-being were examined as a function of perception of family connectedness. Comparisons were also made between adolescents with visible and invisible conditions. RESULTS: Adolescents with chronic conditions had lower emotional well-being scores, worried more about dying soon and about school or future work, and had poorer body image. For students with and without chronic conditions, higher emotional well-being scores were significantly related to higher levels of family connectedness. The best explanatory variables of emotional well-being were body image, family connectedness, concerns about school and future work, having a disability, and worry about peer relationships, accounting together for 36% of the variance in the outcome variable. No differences were found between adolescents with visible and invisible conditions. CONCLUSIONS: Although adolescents with chronic conditions do less well than adolescents without chronic conditions, having a disability is not the most influential factor on emotional well-being. Family connectedness is of fundamental importance for adolescents' emotional health.

Adolescent↗

Acute, severe noncardiac conditions in patients with acute myocardial infarction.

PURPOSE: The study's purpose was to determine the prevalence and prognostic importance of acute, severe, noncardiac conditions present at the time of an acute myocardial infarction (AMI). METHODS: We identified consecutive patients with AMI who were discharged from Yale-New Haven Hospital between January 1, 1997, and June 30, 2000. Acute, noncardiac conditions that were present at admission were abstracted from patient records and graded by severity (imminent threat to life; other significant condition that would warrant admission). We examined the prognostic importance of these conditions on hospital mortality in multivariable logistic models. The study included 1145 patients with AMI, of whom 8.5% (n=97) presented with an acute, life-threatening, noncardiac condition at admission and 19.5% (n=223) presented with another significant noncardiac condition. RESULTS: Hospital mortality was 25.8% and 9.0%, respectively, for patients who presented with life-threatening and other significant noncardiac conditions, compared with 4.6% for patients without either of these conditions. In multivariable analysis, life-threatening noncardiac conditions were associated with increased hospital mortality after adjusting for demographic factors, medical history, clinical presentation, cardiac severity, and initial therapy (odds ratio 2.5; 95% confidence interval [CI], 1.2-5.2). No increased hospital mortality risk was found for other significant noncardiac conditions in the risk-adjusted analyses (odds ratio 1.0; 95% CI, 0.5-1.7). CONCLUSIONS: A subgroup of patients with AMI presented with a life-threatening noncardiac condition, which was associated with a marked increase in the risk of death during the hospitalization. Despite the excessive mortality risk associated with concomitant noncardiac conditions, this subset of patients with AMI are poorly described in current literature.

Acute Disease↗

Chronic health conditions in adult survivors of childhood cancer.

BACKGROUND: Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. RESULTS: Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. CONCLUSIONS: Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.

Adolescent↗